## Protocol Section
### Identification Module
**NCT ID:** NCT01005979

**Brief Title:** A Phase I Trial Using Cyclophosphamide, Rituximab and Revlimid (CR2) for the Treatment of Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL) and Small Lymphocytic Lymphoma (SLL)

**Official Title:** A Phase I Trial Using Cyclophosphamide, Rituximab and Revlimid (CR2) for the Treatment of Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL) and SLL

#### Organization Study ID Info
**ID:** IRB00024085
#### Organization
**Class:** OTHER
**Full Name:** Emory University
#### Secondary ID Infos
**Domain:** Other
**ID:** WCI1642-09
**Type:** OTHER
### Status Module
#### Expanded Access Info
#### Last Update Post Date
**Date:** 2014-08-13

**Type:** ESTIMATED

**Last Update Submit Date:** 2014-08-12

**Overall Status:** TERMINATED

#### Primary Completion Date
**Date:** 2012-10

**Type:** ACTUAL

#### Start Date
**Date:** 2010-07

**Status Verified Date:** 2014-08

#### Study First Post Date
**Date:** 2009-11-01
**Type:** ESTIMATED
**Study First Submit Date:** 2009-09-30
**Study First Submit QC Date:** 2009-10-30
**Why Stopped:** Slow Accrual
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Celgene Corporation

#### 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:** The purpose of this study is to determine the maximum tolerated dose (MTD), safety and toxicity when cyclophosphamide, rituximab and lenalidomide (Revlimid) are combined for the treatment of relapsed/refractory of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

### Conditions Module

**Conditions:**

- Leukemia, Lymphocytic, Chronic, B-Cell

- Chronic Lymphocytic Leukemia

- Lymphoma, Small Lymphocytic

**Keywords:**

- Leukemia, Lymphocytic, Chronic, B-Cell

- Chronic Lymphocytic Leukemia

- Lymphoma, Small Lymphocytic

- Lymphoma

- Leukemia

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 6

**Type:** ACTUAL

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: Lenalidomide, Rituximab, and Cyclophosphamide

**Label:** A

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- A

**Description:** COHORT 1: Cyclophosphamide 250 mg/m2 day 1, 2 and 3, Rituximab 500 mg/m2 i.v. day 1, Lenalidomide 2.5 mg/day starting day 8-28 of Cycle 1 and then daily on Days 1-28 of subsequent cycles

COHORT 2: Cyclophosphamide 250mg/m2 day 1, 2 and 3. Rituximab 500 mg.m2 i.v. daY Lenalidomide 5 mg/day starting day 8 -28 of Cycle 1 and then daily on Days 1-28 of subsequent cycles

COHORT 3: Cyclophosphamide 250mg/m2 day 1, 2 and 3, Rituximab 500 mg.m2 i.v. day 1, Lenalidomide 10 mg/day starting day 8 -28 of Cycle 1 and then daily on Days 1-28 of subsequent cycles

COHORT 4: Cyclophosphamide 250mg/m2 day 1, 2 and 3, Rituximab 500 mg.m2 i.v. day 1, Lenalidomide 15 mg/day starting day 8 -28 of Cycle 1 and then daily on Days 1-28 of subsequent cycles

Patients will receive a total of 6-8 cycles.

**Name:** Lenalidomide, Rituximab, and Cyclophosphamide

**Other Names:**

- Revlimid

- Rituxan

- Mab Thera

- Endoxan

- Cytoxan

- Neosar

- Procytox

- Revimmune

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** The primary endpoint is to determine the maximum tolerated dose of lenalidomide in combination with cyclophosphamide and rituximab for the treatment of CLL or SLL.

**Time Frame:** Day 28 of the first cycle of chemotherapy

#### Secondary Outcomes

**Measure:** Assess response criteria, including complete response rate, survival at 1 year, time to progression, duration of response, and eradication of minimal residual disease.

**Time Frame:** Response will be measured after 4 cycles, at the end of treatment and then every 3 months post treatment.

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.
2. Age ≥ 18 years at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Relapsed/refractory B-cell CLL or SLL
5. All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 2 weeks prior to treatment in this study.
6. Patients must have received at least one prior therapy and must meet the NCI Working Group (NCI WG) Criteria for treatment of B-CLL as described in Appendix D.
7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry (see Appendix C).
8. Laboratory test results within these ranges (unless related to CLL involvement):

   * Absolute neutrophil count ≥ 1000 /mm3
   * Platelet count ≥ 50,000/mm³
   * Serum creatinine ≤ 1.5 mg/dL. Serum creatinine \> 1.5 mg/dL requires creatinine clearance of ≥ 60 mL/min by Cockroft-Gault formula.
   * Total bilirubin ≤ 1.5 mg/dL
   * Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 2 x upper limit of normal (ULN) or ≤ 5 x ULN if hepatic metastases are present.
9. Disease free of second malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast.
10. Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-International Units (mIU)/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix A: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, AND also Appendix B: Education and Counseling Guidance Document.
11. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid \[ASA\] may use warfarin or low molecular weight heparin).

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
4. Evidence of laboratory tumor lysis syndrome (TLS) by Cairo-Bishop criteria (Appendix J) (subjects may be enrolled upon correction of electrolyte abnormalities).
5. Use of any other experimental drug or therapy within 28 days of baseline.
6. Known hypersensitivity to thalidomide.
7. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
8. Any prior use of lenalidomide.
9. Concurrent use of other anti-cancer agents or treatments.
10. Known positive for HIV or infectious hepatitis, type A, B or C.

**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 Winship Cancer Institute

**Name:** Rajni Sinha, MD

**Role:** PRINCIPAL_INVESTIGATOR

## 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: D000006402

- Term: Hematologic Diseases

- ID: D000015448

- Term: Leukemia, B-Cell

- ID: D000002908

- Term: Chronic Disease

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10945

- Name: Leukemia

- Relevance: HIGH

- As Found: Leukemia

- ID: M10951

- Name: Leukemia, Lymphoid

- Relevance: HIGH

- As Found: Lymphocytic Leukemia

- ID: M18116

- Name: Leukemia, Lymphocytic, Chronic, B-Cell

- Relevance: HIGH

- As Found: Leukemia, Lymphocytic, Chronic, B-Cell

- ID: M11220

- Name: Lymphoma

- Relevance: HIGH

- As Found: Lymphoma

- 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: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M18115

- Name: Leukemia, B-Cell

- Relevance: LOW

- As Found: Unknown

- ID: M6147

- Name: Chronic Disease

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: T1308

- Name: Chronic Lymphocytic Leukemia

- Relevance: HIGH

- As Found: Chronic Lymphocytic Leukemia

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: HIGH

- As Found: Chronic

- ID: T3543

- Name: Lymphosarcoma

- Relevance: HIGH

- As Found: Lymphoma

### Condition Browse Module - Meshes

- ID: D000008223

- Term: Lymphoma

- ID: D000007938

- Term: Leukemia

- ID: D000007945

- Term: Leukemia, Lymphoid

- ID: D000015451

- Term: Leukemia, Lymphocytic, Chronic, 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: D000020533

- Term: Angiogenesis Inhibitors

- ID: D000043924

- Term: Angiogenesis Modulating Agents

- ID: D000006133

- Term: Growth Substances

- ID: D000006131

- Term: Growth Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M6727

- Name: Cyclophosphamide

- Relevance: HIGH

- As Found: Cycle

- ID: M373

- Name: Rituximab

- Relevance: HIGH

- As Found: Healthy

- ID: M1725

- Name: Lenalidomide

- Relevance: HIGH

- As Found: Respiratory

- 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: M22318

- Name: Angiogenesis Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M9231

- Name: Growth Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000003520

- Term: Cyclophosphamide

- ID: D000069283

- Term: Rituximab

- ID: D000077269

- Term: Lenalidomide

### Misc Info Module

- Version Holder: 2024-05-24
