## Protocol Section
### Identification Module
**NCT ID:** NCT00634179

**Brief Title:** A Phase I/II Trial of VR-CHOP in Lymphoma Patients

**Official Title:** A Phase I/II Trial of VR-CHOP for Patients With Untreated Follicular Lymphoma and Other Low Grade B-Cell Lymphomas

#### Organization Study ID Info
**ID:** IRB00002996
#### Organization
**Class:** OTHER
**Full Name:** Emory University
#### Secondary ID Infos
**Domain:** Winship Cancer Institute
**ID:** X05215
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2015-11

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2016-10-27

**Type:** ESTIMATED

**Last Update Submit Date:** 2016-09-21

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2015-11

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2016-03-15

**Type:** ESTIMATED

**Results First Submit Date:** 2016-02-17

**Results First Submit QC Date:** 2016-02-17

#### Start Date
**Date:** 2008-02

**Status Verified Date:** 2016-09

#### Study First Post Date
**Date:** 2008-03-12
**Type:** ESTIMATED
**Study First Submit Date:** 2008-02-11
**Study First Submit QC Date:** 2008-03-11
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Millennium Pharmaceuticals, Inc.

#### Lead Sponsor

**Class:** OTHER

**Name:** Emory University

#### Responsible Party

**Investigator Affiliation:** Emory University

**Investigator Full Name:** Christopher R. Flowers

**Investigator Title:** Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This is an open-label (doctors and patients know which drug will be given), single center, phase 1/2 clinical trial. The primary objective is to determine whether VR-CHOP provides benefit to patients with previously untreated indolent non-Hodgkin's lymphomas (NHL).

**Detailed Description:** This study will assess whether adding bortezomib (Velcade) to R-CHOP (in a new combination called VR-CHOP) can further improve outcomes in patients with indolent NHL who have not previously received treatment.

Patients who are eligible to take part in the study will receive VR-CHOP at the doses of Velcade and vincristine established in phase 1. Patients will receive VR-CHOP for up to 8 cycles of treatment (each of 21 days duration). During treatment, patients will be assessed for their response to therapy and for possible side effects. All patients will go on to receive maintenance therapy after completion of their initial treatment as designed by the protocol.

### Conditions Module

**Conditions:**

- Lymphoma, B-Cell

- Follicular Lymphoma

**Keywords:**

- Lymphoma

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 37

**Type:** ACTUAL

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** INDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.

MAINTENANCE: Patients achieving complete response (CR) receive rituximab IV once every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or partial response (PR) receive rituximab IV and bortezomib once weekly for 4 weeks every 6 months for up to 2 years in the absence of disease progression or unacceptable toxicity.

**Intervention Names:**

- Drug: Bortezomib

- Biological: Rituximab

- Drug: Doxorubicin

- Drug: Cyclophosphamide

- Drug: Vincristine

- Drug: Prednisone

**Label:** Treatment (VR-CHOP regimen)

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Treatment (VR-CHOP regimen)

**Description:** Bortezomib 1.6 mg/m² given on days 1 and 8

**Name:** Bortezomib

**Other Names:**

- Velcade

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Treatment (VR-CHOP regimen)

**Description:** Rituximab 375 mg/m²

**Name:** Rituximab

**Other Names:**

- Rituxin

- MabThera

**Type:** BIOLOGICAL

#### Intervention 3

**Arm Group Labels:**

- Treatment (VR-CHOP regimen)

**Description:** Doxorubicin 50 mg/m²

**Name:** Doxorubicin

**Other Names:**

- Adriamycin

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- Treatment (VR-CHOP regimen)

**Description:** Cyclophosphamide 750 mg/m²

**Name:** Cyclophosphamide

**Other Names:**

- Neosar

**Type:** DRUG

#### Intervention 5

**Arm Group Labels:**

- Treatment (VR-CHOP regimen)

**Description:** Vincristine 1.4 mg/m² (capped at 1.5 mg maximum) given on day 1

**Name:** Vincristine

**Other Names:**

- Oncovin

**Type:** DRUG

#### Intervention 6

**Arm Group Labels:**

- Treatment (VR-CHOP regimen)

**Description:** Prednisone 100 mg/day given orally on days 1-5

**Name:** Prednisone

**Other Names:**

- Deltasone

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** INDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.

**Measure:** Maximal Tolerated Doses of Bortezomib and Vincristine When Used in Combination of Bortezomib, Rituximab and the CHOP Chemotherapy Regimen (Phase I)

**Time Frame:** Cycle 1 for MTD, following completion of therapy for CR, up to 24 weeks

#### Secondary Outcomes

**Description:** Response was assessed by computerized tomography (CT) after every 2 cycles of induction therapy, one time at least 4 weeks after completing induction (i.e., prior to maintenance), and then every 3 months while on maintenance therapy. At the conclusion of maintenance therapy, patients underwent one post-treatment scan, with further scans completed at the discretion of the treating physician. Positron emission tomography was permitted but only CT measurements were used to determine response.

**Measure:** An Estimate of the Overall Response Rate (ORR)(Complete Response [CR] + CR Unconfirmed [CRu] + Partial Response [PR]) to Bortezomib and Rituximab (VR)-CHOP According to International Workshop to Standardize Response Criteria (IWRC) Criteria

**Time Frame:** Following completion of therapy, up to 2 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Tissue diagnosis of a previously untreated, cluster of differentiation antigen 20+ (CD20+), B-cell non-Hodgkin lymphoma.

  * For the Phase 1 trial: patients with any of the following diagnoses are eligible:

    * Follicular Lymphomas (Grade 1, 2, 3a, 3b)
    * Small Lymphocytic Lymphoma
    * Marginal Zone Lymphomas
  * For the Phase 2 trial: patients with any of the following diagnoses are eligible:

    * Follicular Lymphomas (Grade 1, 2, 3a)
    * Small Lymphocytic Lymphoma
    * Marginal Zone Lymphomas
* Patients with follicular or other low-grade lymphoma must have an indication for treatment based on modified Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria or a Follicular Lymphoma International Prognostic Index (FLIPI) score ≥ 3.

  * Indications for treatment based on modified GELF criteria include any one of the following:

    * B symptoms or other lymphoma-related symptoms
    * Involvement of 3 nodal sites, each with a diameter of 3 cm
    * Any nodal or extranodal tumor mass with a diameter of 7 cm
    * Splenomegaly greater than 16 cm by CT scan.
    * Pleural effusions or peritoneal ascites
    * Cytopenias (leukocytes \< 1.0 x 10 /L and/or platelets \< 100 x 10/L)
    * Leukemia (\> 5.0 x 10 /L circulating malignant cells)
  * Indications for treatment based on FLIPI criteria include any three of the following:

    * Age ≥ 60 years
    * Ann Arbor stage III or IV
    * Hemoglobin level \< 120 g/L
    * Number of nodal areas involved \> 4
    * Serum lactate dehydrogenase (LDH) level \> normal
* Only chemotherapy-naïve subjects are eligible. Subjects may have received prednisone (\< 2 months of therapy) or radiation ≤ 2 sites of therapy.
* Voluntary written informed consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
* Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
* Female patients of child bearing potential must have a negative β-human chorionic gonadotropin (β-hCG) test.
* Male subject agrees to use an acceptable method for contraception for the duration of the study.
* ≥ 18 years of age at the time of registration.
* Patients must have adequate renal function as demonstrated by a serum creatinine \< 1.5 mg/dl unless felt to be secondary to lymphoma.
* Must have an alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3.5 the upper limit of normal and a total bilirubin ≤ 2.0 mg/dL unless secondary to lymphoma.
* Must have a cardiac left ventricular ejection fraction ≥ 50%.
* At least 1 measurable tumor mass (greater than 1.5 cm in the longest dimension and greater than 1.0 cm in the short axis).
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

Exclusion Criteria:

* Subject with primary or secondary central nervous system (CNS) lymphoma (current or previously treated) will not be eligible.
* A history of unrelated (non-lymphomatous) neoplasm within the past 10 years other than non-melanoma skin cancer or in-situ cervix cancer. Subjects with a prior diagnosis of malignancy more than 10 years may be entered into the study at the discretion of the Principal Investigator.
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
* Patient has received other investigational drugs with 14 days before enrollment.
* Patient has hypersensitivity to boron or mannitol.
* Female subject is pregnant or breast-feeding. Chemotherapeutic agents are known to have teratogenic effects on developing embryos and to cause chromosomal damage to gametes. These agents also cause bone marrow suppression and can be excreted in milk. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
* Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment.
* Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
* Patient has a platelet count of \< 10 x 10¹⁰/L (unless due to bone marrow involvement with lymphoma documented within 14 days before enrollment).
* Patient has an absolute neutrophil count of \< 1.0 x 10⁹/L (unless due to bone marrow involvement with lymphoma documented within 14 days before enrollment).
* Patient has a calculated or measured creatinine clearance of \< 20 mL/minute within 14 days before enrollment.
* Presence of antibodies to HIV.
* Subject unwilling to give informed consent.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Atlanta

**Country:** United States

**Facility:** Emory University Winship Cancer Institute

**State:** Georgia

**Zip:** 30322

#### Overall Officials

**Official 1:**

**Affiliation:** Emory University

**Name:** Christopher Flowers, MD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** Sinha R, Kaufman JL, Khoury HJ Jr, King N, Shenoy PJ, Lewis C, Bumpers K, Hutchison-Rzepka A, Tighiouart M, Heffner LT, Lechowicz MJ, Lonial S, Flowers CR. A phase 1 dose escalation study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone for untreated follicular lymphoma and other low-grade B-cell lymphomas. Cancer. 2012 Jul 15;118(14):3538-48. doi: 10.1002/cncr.26660. Epub 2012 Jan 3.

**PMID:** 22535574

**Citation:** Cohen JB, Switchenko JM, Koff JL, Sinha R, Kaufman JL, Khoury HJ, Bumpers N, Colbert A, Hutchison-Rzepka A, Nastoupil LJ, Heffner LT, Langston AA, Lechowicz MJ, Lonial S, Flowers CR. A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma. Br J Haematol. 2015 Nov;171(4):539-46. doi: 10.1111/bjh.13637. Epub 2015 Aug 7.

**PMID:** 26248505

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000008206

- Term: Lymphatic Diseases

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

- ID: D000008228

- Term: Lymphoma, Non-Hodgkin

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M11220

- Name: Lymphoma

- Relevance: HIGH

- As Found: Lymphoma

- ID: M11221

- Name: Lymphoma, Follicular

- Relevance: HIGH

- As Found: Follicular lymphoma

- ID: M18828

- Name: Lymphoma, B-Cell

- Relevance: HIGH

- As Found: Lymphoma, B-Cell

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11203

- Name: Lymphatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11222

- Name: Lymphoma, Non-Hodgkin

- Relevance: LOW

- As Found: Unknown

- ID: T3543

- Name: Lymphosarcoma

- Relevance: HIGH

- As Found: Lymphoma

- ID: T2361

- Name: Follicular Lymphoma

- Relevance: HIGH

- As Found: Follicular lymphoma

- ID: T640

- Name: B-cell Lymphoma

- Relevance: HIGH

- As Found: Lymphoma, B-Cell

### Condition Browse Module - Meshes

- ID: D000008223

- Term: Lymphoma

- ID: D000008224

- Term: Lymphoma, Follicular

- ID: D000016393

- Term: Lymphoma, B-Cell

### Intervention Browse Module - Ancestors

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018501

- Term: Antirheumatic Agents

- ID: D000018906

- Term: Antineoplastic Agents, Alkylating

- ID: D000000477

- Term: Alkylating Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000019653

- Term: Myeloablative Agonists

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000903

- Term: Antibiotics, Antineoplastic

- ID: D000059005

- Term: Topoisomerase II Inhibitors

- ID: D000059003

- Term: Topoisomerase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000000893

- Term: Anti-Inflammatory Agents

- ID: D000005938

- Term: Glucocorticoids

- ID: D000006728

- Term: Hormones

- ID: D000006730

- Term: Hormones, Hormone Substitutes, and Hormone Antagonists

- ID: D000018931

- Term: Antineoplastic Agents, Hormonal

- ID: D000000972

- Term: Antineoplastic Agents, Phytogenic

- ID: D000050257

- Term: Tubulin Modulators

- ID: D000050256

- Term: Antimitotic Agents

- ID: D000050258

- Term: Mitosis Modulators

### Intervention Browse Module - Browse Branches

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Infe

- Name: Anti-Infective Agents

### Intervention Browse Module - Browse Leaves

- ID: M14121

- Name: Prednisone

- Relevance: HIGH

- As Found: Min

- ID: M6727

- Name: Cyclophosphamide

- Relevance: HIGH

- As Found: Cycle

- ID: M373

- Name: Rituximab

- Relevance: HIGH

- As Found: Healthy

- ID: M7492

- Name: Doxorubicin

- Relevance: HIGH

- As Found: Women

- ID: M227339

- Name: Liposomal doxorubicin

- Relevance: LOW

- As Found: Unknown

- ID: M17495

- Name: Vincristine

- Relevance: HIGH

- As Found: Volume

- ID: M376

- Name: Bortezomib

- Relevance: HIGH

- As Found: 14 days

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20942

- Name: Antineoplastic Agents, Alkylating

- Relevance: LOW

- As Found: Unknown

- ID: M3820

- Name: Alkylating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4224

- Name: Antibiotics, Antitubercular

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M4217

- Name: Anti-Inflammatory Agents

- Relevance: LOW

- As Found: Unknown

- ID: M9047

- Name: Glucocorticoids

- Relevance: LOW

- As Found: Unknown

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: M9788

- Name: Hormone Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M20966

- Name: Antineoplastic Agents, Hormonal

- Relevance: LOW

- As Found: Unknown

- ID: M26197

- Name: Tubulin Modulators

- Relevance: LOW

- As Found: Unknown

- ID: M26196

- Name: Antimitotic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000011241

- Term: Prednisone

- ID: D000003520

- Term: Cyclophosphamide

- ID: D000069283

- Term: Rituximab

- ID: D000004317

- Term: Doxorubicin

- ID: D000014750

- Term: Vincristine

- ID: D000069286

- Term: Bortezomib

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** Phase I: Induction

**Description:** Phase I will identify the maximal tolerated doses of bortezomib and vincristine when used in a combination of bortezomib, rituximab and the CHOP chemotherapy regimen.

**ID:** EG000

**Other Num Affected:** 16

**Other Num at Risk:** 19

**Serious Number Affected:** 3

**Serious Number At Risk:** 19

**Title:** Phase I: Induction

**Group ID:** EG001

**Title:** Phase II: Maintenance

**Description:** In Phase II, the trial will evaluate the efficacy and safety of the MTD combination of VELCADE and rituximab-CHOP in additional subjects who have untreated follicular B-NHL. (Grade 1, 2, 3a), small lymphocytic lymphoma, or marginal zone lymphoma.

**ID:** EG001

**Other Num Affected:** 22

**Other Num at Risk:** 29

**Serious Number Affected:** 1

**Serious Number At Risk:** 29

**Title:** Phase II: Maintenance

**Frequency Threshold:** 0

#### Other Events

**Term:** Neutropenia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

**Source Vocabulary:** 

**Term:** Thrombocytopenia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

**Source Vocabulary:** 

**Term:** Nausea

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** 

**Term:** Neuropathy

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** 

**Term:** Fatigue

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** 

**Term:** Vomiting

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** 

**Term:** Diarrhea

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** 

**Term:** Rash

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Skin and subcutaneous tissue disorders

**Source Vocabulary:** 

**Term:** Dyspepsia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** 

**Term:** Low Potassium

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** 

**Term:** Pain

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** 

**Term:** Anemia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

**Source Vocabulary:** 

**Term:** Febrile Neutropenia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

**Source Vocabulary:** 

**Term:** Hyperglycemia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** 

**Term:** Extravasation

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

**Source Vocabulary:** 

**Term:** Fever

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Immune system disorders

**Source Vocabulary:** 

**Term:** Hypoxia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

**Source Vocabulary:** 

**Term:** Parotitis

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Immune system disorders

**Source Vocabulary:** 

**Term:** Weakness

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** 

**Term:** Tachycardia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** 

#### Serious Events

**Term:** Thrombosis

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 19

**Group ID:** EG001

**Num At Risk:** 29

**Term:** Fatigue

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

##### Stats

**Group ID:** EG000

**Num At Risk:** 19

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 29

**Term:** Vomiting

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

##### Stats

**Group ID:** EG000

**Num At Risk:** 19

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 29

**Term:** Diarrhea

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

##### Stats

**Group ID:** EG000

**Num At Risk:** 19

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 29

**Term:** Pain

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

##### Stats

**Group ID:** EG000

**Num At Risk:** 19

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 29

**Term:** Febrile Neutropenia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 19

**Group ID:** EG001

**Num At Risk:** 29

**Term:** Anxiety/Depression

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Psychiatric disorders

##### Stats

**Group ID:** EG000

**Num At Risk:** 19

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 29

**Term:** Cellulitis

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Skin and subcutaneous tissue disorders

##### Stats

**Group ID:** EG000

**Num At Risk:** 19

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 29

**Term:** Dehydration

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

##### Stats

**Group ID:** EG000

**Num At Risk:** 19

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 29

**Term:** Dyspnea

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

##### Stats

**Group ID:** EG000

**Num At Risk:** 19

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 29

**Term:** Extravasation

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 19

**Group ID:** EG001

**Num At Risk:** 29

**Term:** Prolonged QT Interval

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

##### Stats

**Group ID:** EG000

**Num At Risk:** 19

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 29

**Term:** Urinary Tract Infection

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

##### Stats

**Group ID:** EG000

**Num At Risk:** 19

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 29

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 37

**Units:** Participants

### Group

**ID:** BG000

**Title:** Treatment (VR-CHOP Regimen)

**Description:** INDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.

MAINTENANCE: Patients achieving complete response (CR) receive rituximab IV once every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or partial response (PR) receive rituximab IV and bortezomib once weekly for 4 weeks every 6 months for up to 2 years in the absence of disease progression or unacceptable toxicity.

### Measure

#### Measurement

**Group ID:** BG000

**Lower Limit:** 28

**Upper Limit:** 71

**Value:** 58

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 17

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 20

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** American Indian or Alaska Native

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Asian

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Native Hawaiian or Other Pacific Islander

#### Measurement

**Group ID:** BG000

**Value:** 11

**Category Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 26

**Category Title:** White

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** More than one race

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 37

**Class Title:** United States

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** FULL_RANGE
**Parameter Type:** MEDIAN
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Race (NIH/OMB)
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** NUMBER
**Title:** Region of Enrollment
**Unit of Measure:** participants
**Population Description:** A total of 37 patients were enrolled on this study. However, not all patients participated in both phases of this study. For phase I, 19 patients were enrolled, and for phase II, 30 patients were enrolled.
## Results Section - More Information Module
### Certain Agreement
**PI Sponsor Employee:** True
### Point of Contact
**Email:** crflowe@emory.edu
**Organization:** Emory University
**Phone:** 404-778-3935
**Title:** Christopher R. Flowers, MD, MS
## Results Section - Outcome Measures Module
### Outcome Measure 1
### Outcome Measure 2
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 0.63
- **Spread:** 
- **Upper Limit:** 1.88
- **Value:** 1.62
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 13
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 19
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 6
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 10
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 19
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 29
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** INDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.
**Dispersion Type:** 95% Confidence Interval
**Parameter Type:** NUMBER
**Reporting Status:** POSTED
**Time Frame:** Cycle 1 for MTD, following completion of therapy for CR, up to 24 weeks
**Title:** Maximal Tolerated Doses of Bortezomib and Vincristine When Used in Combination of Bortezomib, Rituximab and the CHOP Chemotherapy Regimen (Phase I)
**Type:** PRIMARY
**Unit of Measure:** mg/m^2
##### Group
**Description:** Maximal tolerated dose (MTD) of bortezomib when vincristine is capped at 1.5 mg
**ID:** OG000
**Title:** MTD of Bortezomib With Vincristine Capped at 1.5 mg
#### Outcome Measure 2
**Description:** Response was assessed by computerized tomography (CT) after every 2 cycles of induction therapy, one time at least 4 weeks after completing induction (i.e., prior to maintenance), and then every 3 months while on maintenance therapy. At the conclusion of maintenance therapy, patients underwent one post-treatment scan, with further scans completed at the discretion of the treating physician. Positron emission tomography was permitted but only CT measurements were used to determine response.
**Parameter Type:** NUMBER
**Reporting Status:** POSTED
**Time Frame:** Following completion of therapy, up to 2 years
**Title:** An Estimate of the Overall Response Rate (ORR)(Complete Response [CR] + CR Unconfirmed [CRu] + Partial Response [PR]) to Bortezomib and Rituximab (VR)-CHOP According to International Workshop to Standardize Response Criteria (IWRC) Criteria
**Type:** SECONDARY
**Unit of Measure:** participants
##### Group
**Description:** INDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.
**ID:** OG000
**Title:** Phase I: Induction
##### Group
**Description:** INDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.

MAINTENANCE: Patients achieving CR receive rituximab IV once every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or PR receive rituximab IV and bortezomib once weekly for 4 weeks every 6 months for up to 2 years in the absence of disease progression or unacceptable toxicity.

Bortezomib: Bortezomib 1.6 mg/m² given on days 1 and 8

Rituximab: Rituximab 375 mg/m²

Doxorubicin: Doxorubicin 50 mg/m²

Cyclophosphamide: Cyclophosphamide 750 mg/m²

Vincristine: Vincristine 1.4 mg/m² (capped at 1.5 mg maximum) given on day 1

Prednisone: Prednisone 100 mg/day given orally on
**ID:** OG001
**Title:** Phase II: Maintenance
### Participant Flow Module
#### Group
**Description:** Phase I will identify the maximal tolerated doses of bortezomib and vincristine when used in a combination of bortezomib, rituximab and the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimen.

In Phase II, the trial will evaluate the efficacy and safety of the MTD combination of VELCADE and rituximab-CHOP in additional subjects who have untreated follicular B-cell non-Hodgkin's lymphoma (B-NHL)(Grade 1, 2, 3a), small lymphocytic lymphoma, or marginal zone lymphoma.
**ID:** FG000
**Title:** Treatment (VR-CHOP Regimen)
#### Period
**Title:** Phase I: Induction
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 19
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 19
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
#### Period
**Title:** Phase II: Maintenance
##### Withdraw
**Type:** Diagnosis changed after re-review
###### Reason
**Group ID:** FG000
**Number of Subjects:** 1
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 30
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 29
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 1
**Pre-Assignment Details:** A total of 37 patients were enrolled. However, not all patients participated in both phases of this study. For phase I, 19 patients were enrolled, and for phase II, 30 patients were enrolled.
**Recruitment Details:** All patients were recruited from Winship Cancer Institute of Emory University.
**Has Results:** True