Fludarabine and Rituximab With or Without Pixantrone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma

NCT ID: NCT00551239

Last Updated: 2020-10-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine and pixantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving fludarabine together with rituximab is more effective with or without pixantrone in treating indolent non-Hodgkin lymphoma.

PURPOSE: This randomized phase III trial is studying fludarabine and rituximab to compare how well they work with or without pixantrone in treating patients with relapsed or refractory indolent non-Hodgkin lymphoma.

Detailed Description

OBJECTIVES:

Primary

• To compare the progression-free survival (PFS) of patients with relapsed or refractory indolent non-Hodgkin lymphoma treated with fludarabine phosphate and rituximab with vs without pixantrone.

Secondary

• To compare the overall objective response rate (complete response [CR], unconfirmed complete response [CRu], and partial response [PR]) in these patients.
• To compare the CR and CRu rate in these patients.
• To compare the duration of response and time to progression in these patients.
• To compare the overall survival and disease-specific survival of these patients.
• To compare the safety (including cardiac safety) and tolerability of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are stratified by Follicular Lymphoma International Prognostic Index (FLIPI) score (0 or 1 vs ≥ 2), number of prior treatments (1 or 2 vs > 2), and prior anti-CD20 regimen (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I (control): Patients receive rituximab IV on day 1 and fludarabine phosphate IV on days 2-4. Treatment repeats every 28 days for up to 6 courses* in the absence of unacceptable toxicity or disease progression.
• Arm II: Patients receive rituximab and fludarabine phosphate as in arm I. Patients also receive pixantrone IV on day 2. Treatment repeats every 28 days for up to 6 courses* in the absence of unacceptable toxicity or disease progression.

NOTE: *Only patients achieving complete response, unconfirmed complete response, or partial response after 4 courses receive courses 5 and 6.

After completion of study therapy, patients are followed periodically for up to 5 years.

Conditions

Leukemia; Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT

Study Groups

Arm I (control)

Patients receive rituximab IV on day 1 and fludarabine phosphate IV on days 2-4. Treatment repeats every 28 days for up to 6 courses.

Group Type: ACTIVE_COMPARATOR

rituximab

Intervention Type: BIOLOGICAL

Given IV

fludarabine phosphate

Intervention Type: DRUG

Given IV

Arm II

Patients receive rituximab and fludarabine phosphate as in arm I. Patients also receive pixantrone IV on day 2. Treatment repeats every 28 days for up to 6 courses.

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

Given IV

fludarabine phosphate

Intervention Type: DRUG

Given IV

pixantrone dimaleate

Intervention Type: DRUG

Given IV

Interventions

rituximab

Given IV

Intervention Type: BIOLOGICAL

fludarabine phosphate

Given IV

Intervention Type: DRUG

pixantrone dimaleate

Given IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with spleen or bone marrow as only site of disease are not eligible
• Patients must have received at least 1 prior therapy

• Prior treatment with fludarabine phosphate, doxorubicin, and/or mitoxantrone is allowed provided there was a response to treatment (complete response [CR], unconfirmed complete response [CRu], or partial response [PR]) that lasted ≥ 8 months from the start of that therapy
• Patients refractory to treatments other than anthracycline/anthracenedione, fludarabine phosphate, or rituximab-containing regimens may be eligible for this study
• No HIV-related lymphoma
• No active CNS involvement based on clinical evaluation

• If the patient requires a diagnostic lumbar puncture due to high risk criteria (i.e., sinus involvement, high LDH, high International Prognostic Index score, or bone marrow involvement), intrathecal chemotherapy (which may include methotrexate, cytarabine, and corticosteroids) may be administered according to institutional standards

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 3 months
• ECOG performance status 0-1
• LVEF ≥ 50% by MUGA scan
• Creatinine ≤ 1.5 times ULN
• Total bilirubin ≤ 1.5 times ULN (CTC grade 1) (patients with Gilbert's syndrome or other hereditary bilirubin defects may be eligible regardless of bilirubin levels)
• AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN if there is hepatic involvement with lymphoma)
• ANC ≥ 1,500/mm³ (≥ 500/mm³ if bone marrow is involved)
• Platelet count ≥ 75,000/mm³ (with no bleeding)
• No known hypersensitivity to the study drugs or to their excipients
• No known type I hypersensitivity or anaphylactic reactions to murine proteins or to any component of rituximab
• No clinically significant cardiovascular abnormalities (i.e., NYHA class III-IV heart disease), including myocardial infarction within the past 6 months, severe arrhythmia, uncontrolled hypertension, or congestive heart failure requiring current active therapy
• No concurrent serious (NCI CTCAE grade 3-4) infection, including infection requiring oral antibiotics or deep-seated or systemic mycotic infections
• No clinical symptoms suggesting unresolved HIV, hepatitis B, or hepatitis C virus infection

• Patients with seropositivity presumed to be due to prior vaccination against hepatitis B virus or resolved infection are eligible
• No history of another malignancy except curatively treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in remission, or any other cancer from which the patient has been disease-free for 5 years
• No other condition that, in the judgment of the investigator, would place the patient at undue risk, interfere with the results of the study, or make the patient otherwise unsuitable for the study
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after the completion of study treatment

PRIOR CONCURRENT THERAPY:

• Recovered from all acute toxicities from prior therapies (except alopecia or grade 1 peripheral neuropathy)
• No prior treatment with a cumulative dose of doxorubicin equivalent exceeding 450 mg/m²
• More than 4 weeks since prior radiotherapy, chemotherapy, or other therapies for NHL
• More than 5 days since prior systemic corticosteroids for treatment of NHL
• More than 3 months since prior radioimmunotherapy
• More than 4 weeks since prior major thoracic and/or abdominal surgery and recovered
• More than 1 week since prior minor surgery and recovered
• More than 30 days since prior and no other concurrent investigational drugs
• Concurrent corticosteroids (equivalent of 10 mg of prednisone or less per day) allowed provided they are only used to treat concurrent disease (other than NHL)
• No other concurrent systemic anticancer therapy
• No concurrent radiotherapy to target lesions

• Concurrent palliative radiotherapy to preexisting stable sites of nonmeasurable disease allowed

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CTI BioPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Igor Gorbatchevsky, MD

Role: STUDY_CHAIR

CTI BioPharma

Locations

Cell Therapeutics, Incorporated

Seattle, Washington, United States

Countries

United States

Other Identifiers

CDR0000573364

Identifier Type: REGISTRY

Identifier Source: secondary_id

CTI-CRRI-0807003

Identifier Type: -

Identifier Source: org_study_id