## Protocol Section
### Identification Module
**NCT ID:** NCT01493479

**Acronym:** FIZZ

**Brief Title:** Phase II Study of Fractionated 90Y Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy as an Initial Therapy of Follicular Lymphoma

**Official Title:** Phase II Study of Fractionated 90Y Ibritumomab Tiuxetan (Zevalin)

#### Organization Study ID Info
**ID:** 06_DOG05_33
#### Organization
**Class:** OTHER
**Full Name:** The Christie NHS Foundation Trust
### Status Module
#### Completion Date
**Date:** 2015-11-06

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2019-10-15

**Type:** ACTUAL

**Last Update Submit Date:** 2019-10-11

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2011-01

**Type:** ACTUAL

#### Start Date
**Date:** 2007-06-06

**Type:** ACTUAL

**Status Verified Date:** 2019-10

#### Study First Post Date
**Date:** 2011-12-16
**Type:** ESTIMATED
**Study First Submit Date:** 2011-12-14
**Study First Submit QC Date:** 2011-12-15
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Bayer

#### Lead Sponsor

**Class:** OTHER

**Name:** The Christie NHS Foundation Trust

#### Responsible Party

**Investigator Affiliation:** The Christie NHS Foundation Trust

**Investigator Full Name:** Emmie Taylor

**Investigator Title:** Lead Clinical Trial Manager

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** 90Y Ibritumomab tiuxetan (zevalin) has demonstrated consistently high response rates in patients who have received previous treatment for lymphoma. More than two-thirds of the patients who achieve CR go on to experience durable remissions lasting for years. Despite these highly promising clinical results with radioimmunotherapy (RIT) in relapsed follicular lymphoma there is very little data using RIT in previously untreated follicular lymphoma. The objective of this trial is to evaluate the safety and efficacy of two fractions of Zevalin in patients with previously untreated follicular lymphoma in a Phase II study.

### Conditions Module

**Conditions:**

- Follicular Lymphoma

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 76

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: 90Y Ibritumomab tiuxetan

- Drug: Rituximab

**Label:** Fractionated Initial Zevalin

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Fractionated Initial Zevalin

**Description:** 2 x iv infusions of 11.1 MBq/kg. 1st infusion at week 1, 2nd during weeks 9-13. 2nd infusion may be reduced to 7.4MBq/kg in the case of grade 3 haematological toxicity following the 1st infusion.

**Name:** 90Y Ibritumomab tiuxetan

**Other Names:**

- Zevalin

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Fractionated Initial Zevalin

**Description:** All patients receive 2 x iv infusions of 250 mg/m2 Rituximab given 7-8 days apart prior to each zevalin infusion. The 2nd rituximab infusion is given immediately prior to Zevalin.

In addition patients with greater than 20% bone marrow involvement at screening receive rituximab pretreatment prior to entering the main treatment phase of the trial, consisting of 4 x weekly iv doses of rituximab(375 mg/m2). This is followed by a repeat bone marrow biopsy, bone marrow involvement must have fallen to \<= 20% to enter the main treatment phase of the trial.

**Name:** Rituximab

**Other Names:**

- Mabthera

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.

**Measure:** Overall response rate

**Time Frame:** Assessed 3 months post treatment

**Description:** According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.

**Measure:** Combined Complete Response rate

**Time Frame:** Assessed 3 months post treatment

**Description:** According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.

**Measure:** Partial Response Rate

**Time Frame:** Assessed 3 months post treatment

#### Secondary Outcomes

**Measure:** Time to disease progression

**Time Frame:** Assessed 3 months post treatment, repeated assessment up to 5 years follow-up

**Description:** To be assessed for patients achieving a response, including assessment of overall survival and time until next treatment.

**Measure:** Response duration

**Time Frame:** Assessed 3 months post treatment, repeated assessment up to 5 years follow-up

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Patients must have a histologically confirmed CD20 +ve follicular lymphoma grades I to IIIa.
* Patients with at least one of the following symptoms requiring initiation of treatment: (as outlined by the modified BNLI/GELF criteria below)

  * Nodal mass \> 7cm in its greater diameter
  * B symptoms
  * Elevated serum LDH or beta2-microglobulin
  * involvement of at least 3 nodal sites (each with a diameter \> 3 cm)
  * symptomatic splenic enlargement
  * compressive syndrome
* Patients must have an ECOG performance status less than or equal to 2 and an anticipated survival of at least 6 months.
* Patients must have an absolute granulocyte count of above 1,500/mm3, and a platelet count of above 100,000/mm3 post 4 weeks of unlabelled Rituximab. A hemoglobin \>= 8.0 g/dl
* Patients must have adequate renal function (defined as calculated creatinine clearance \> 30 ml/mn), hepatic function (defined as total bilirubin \<1.5 times upper limit of normal), and hepatic transaminases (defined as AST \<5 times upper limit of normal)
* Patients must have given informed consent prior to study entry.

Exclusion Criteria:

* Patients with a mean of \>20% of the intratrabecular marrow space involved with lymphoma on bone marrow biopsy following induction Rituximab therapy.
* Transformed follicular lymphoma and discordant lymphoma
* Patients with active obstructive hydronephrosis.
* Patients with initial disease bulk greater than 10cm.
* Patients with evidence of active infection requiring i.v. antibiotics at the time of study entry.
* Patients with congestive heart failure stage III or IV of NYHA classification, myocardial infraction or unstable angina within 6 months or other serious illness that would preclude evaluation.
* Patients with left VEF \< 40%
* Patients with large pleural or peritoneal effusions.
* Patients with known HIV infection or active HBV (HbsAg positivity) or HCV infection.
* Known Hypersensitivity to murine antibodies or proteins
* Patients who are pregnant or breast-feeding. Male and female patients must agree to use effective contraception for 12 months following 90Y-ibritumomab tiuxetan antibody therapy.
* Patients with prior malignancy other than lymphoma, except for adequately-treated skin cancer, cervical cancer in situ, or other cancer for which the patient has been disease-free for 5 years.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Lille

**Country:** France

**Facility:** Centre Hospitalier Universitaire de Lille

**Location 2:**

**City:** Nantes

**Country:** France

**Facility:** Centre Hospitalier Universitaire de Nantes

**Location 3:**

**City:** Rouen

**Country:** France

**Facility:** Centre Henri Becquerel

**Location 4:**

**City:** London

**Country:** United Kingdom

**Facility:** St George's Hospital

**Location 5:**

**City:** Manchester

**Country:** United Kingdom

**Facility:** The Christie NHS Foundation Trust

**Zip:** M20 4BX

**Location 6:**

**City:** Poole

**Country:** United Kingdom

**Facility:** Poole Hospital NHS Foundation Trust

**Location 7:**

**City:** Southampton

**Country:** United Kingdom

**Facility:** Southampton University Hospital

#### Overall Officials

**Official 1:**

**Affiliation:** The Christie NHS Foundation Trust

**Name:** Timothy Illidge, Prof

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** Illidge TM, Mayes S, Pettengell R, Bates AT, Bayne M, Radford JA, Ryder WD, Le Gouill S, Jardin F, Tipping J, Zivanovic M, Kraeber-Bodere F, Bardies M, Bodet-Milin C, Malek E, Huglo D, Morschhauser F. Fractionated (9)(0)Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of follicular lymphoma: an international phase II study in patients requiring treatment according to GELF/BNLI criteria. J Clin Oncol. 2014 Jan 20;32(3):212-8. doi: 10.1200/JCO.2013.50.3110. Epub 2013 Dec 2.

**PMID:** 24297953

## 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: 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: LOW

- As Found: Unknown

- ID: T2361

- Name: Follicular Lymphoma

- Relevance: HIGH

- As Found: Follicular lymphoma

### Condition Browse Module - Meshes

- ID: D000008223

- Term: Lymphoma

- ID: D000008224

- Term: Lymphoma, Follicular

### Intervention Browse Module - Ancestors

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018501

- Term: Antirheumatic Agents

### 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: M373

- Name: Rituximab

- Relevance: HIGH

- As Found: Healthy

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- 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

### Intervention Browse Module - Meshes

- ID: D000069283

- Term: Rituximab

### Misc Info Module

- Version Holder: 2024-05-24
