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

Phase 2

Completed

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

Interventions: Drug: ixabepilone

Registration Number: NCT00058019

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 51

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (chemotherapy)	ixabepilone	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.

Primary Outcome Measures

Name	Time	Method
Safety and Toxicity of Ixabepilone	up to 3 years	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.
Objective Overall Response Rate	up to 3 years	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.

Secondary Outcome Measures

Name	Time	Method
Time to Progression	up to 3 years	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.
Duration of Response	up to 3 years	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.
Overall Survival	up to 3 years	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.