Ixabepilone in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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This phase II trial is studying how well ixabepilone works in treating patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop cancer cells from dividing so they stop growing or die.

Detailed Description
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OBJECTIVES: I. Determine the objective overall response rate of patients with relapsed or refractory aggressive non-Hodgkin's lymphoma treated with BMS-247550 (ixabepilone). II. Determine the safety and toxicity of this drug in these patients. III. Determine the duration of response, overall survival, and time to progression in patients treated with this drug. OUTLINE: This is a multi-center study. Patients receive ixabepilone intravenously (IV) over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression, unacceptable toxicity, or if the patient becomes a candidate for stem cell transplantation. Patients are followed every 8 weeks until disease progression.

Official Title
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A Phase II Study of Epothilone B Analog BMS-247550 (NSC 710428) in Patients With Relapsed Aggressive Non-Hodgkin's Lymphomas

Conditions
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Anaplastic Large Cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: ixabepilone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following cellular types: Grade III follicular center Diffuse large B-cell Mantle cell Primary mediastinal B-cell Burkitt's High-grade B-cell (Burkitt-like) Anaplastic large cell of 1 of the following subtypes: CD30-positive T-cell Null cell Hodgkin's-like Relapsed or refractory disease after prior standard chemotherapy, meeting criteria for 1of the following cohorts: Cohort 1 (relapsed but chemosensitive): Prior complete response (CR) or partial response (PR) lasting at least 4 weeks after the most recent prior therapy Cohort 2 (refractory): Stable disease or less than a PR after the most recent prior therapy No progressive disease after the most recent prior therapy Measurable disease At least 1 bidimensionally measurable lesion at least 10 mm by conventional techniques or clinical exam Ineligible for or unwilling to undergo hematopoietic stem cell transplantation Patients requiring debulking prior to transplant allowed No known CNS involvement by lymphoma Prior CNS disease that has been successfully treated in patients with relapsed disease exclusively outside of the CNS may be allowed by the principal investigator Performance status - ECOG 0-2 More than 3 months WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,200/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 mg/dL AST/ALT no greater than 2.5 times upper limit of normal Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior allergic reaction or hypersensitivity to compounds containing Cremophor EL or agents of similar chemical or biological composition to BMS-247550 No peripheral neuropathy grade 2 or greater No other currently active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix (previously treated malignancy allowed if considered to be at less than 30% risk of relapse) No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other concurrent uncontrolled illness No colony-stimulating factors (CSFs) within 24 hours of study chemotherapy No CSFs during first course of study therapy No concurrent filgrastim-SD/01 No concurrent immunotherapy See Disease Characteristics At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin) No other concurrent chemotherapy No concurrent hormonal therapy At least 4 weeks since prior radiotherapy No concurrent therapeutic radiotherapy At least 4 weeks since prior surgery Recovered from prior therapy At least 7 days since prior cimetidine No concurrent cimetidine No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No other concurrent anticancer medications No concurrent unconventional therapies, food, or vitamin supplements containing Hypericum perforatum

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (chemotherapy)<br>Patients receive ixabepilone IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression, unacceptable toxicity, or if the patient becomes a candidate for stem cell transplantation. | Drug: ixabepilone<br>* Given IV<br>* Other names: Ixempra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Overall Response Rate | The 1999 international response criteria (http://www.ncbi.nlm.nih.gov/pubmed/10561185) as published by Cheson was used for the definition of target lesions and CT scans were used for response assessment. CR(complete response)/CRu(unconfirmed complete response) requires disappearance of all target lesions; PR (partial response) requires >=50% decrease in the sum of the products of the greatest diameters; Overall Response (OR)=CR/CRu+PR. | up to 3 years | 
| Safety and Toxicity of Ixabepilone | Number of patients experiencing adverse event grade 3 or above. Grade was determined by the National Cancer Institute Common Toxicity Criteria (CTC) version 2.0. Adverse events possibly, probably, or definitely attributed to use of ixabepilone. | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | Duration of response was measured from the time measurement criteria are met for CR(complete response)/CRu(unconfirmed complete response)/PR(partial response), whichever was first recorded, until the first date that PD(progressive disease) was objectively documented. According to the 1999 international response criteria as published by Cheson, CR/CRu is defined as the disappearance of all target lesions; PR is defined as >=50% decrease in the sum of the products of the greatest diameters; PD is defined as >=50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or nonresponders, or appearance of any new lesion during or at the end of therapy. | up to 3 years | 
| Overall Survival | Defined as the time from the first day of therapy to the date of death. If the patient was lost to follow-up, survival was censored on the last date the patient was known to be alive. | up to 3 years | 
| Time to Progression | Defined as the time from the first day of treatment until the date PD(progressive disease) or death is first reported. Patients who died without a reported prior progression was considered to have progressed on the day of their death. Patients who did not progress was censored at the day of their last tumor assessment. According to the 1999 international response criteria as published by Cheson, progression/progressive disease is defined as >=50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or nonresponders, or appearance of any new lesion during or at the end of therapy. | up to 3 years |