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

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

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.

Study Overview

• Status: Completed
• Conditions: 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; Anaplastic Large Cell Lymphoma
• Intervention / Treatment: Drug: ixabepilone

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.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (chemotherapy); 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; Given IV; Other Names: BMS-247550; epothilone B lactam; Ixempra

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: April 7, 2003
• First Submitted That Met QC Criteria: April 8, 2003
• First Posted (Estimate): April 9, 2003

Study Record Updates

• Last Update Posted (Estimate): May 23, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Epstein-Barr Virus Infections; Herpesviridae Infections; Lymphoma, B-Cell; Lymphoma, T-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Recurrence; Lymphoma, Non-Hodgkin; Burkitt Lymphoma; Lymphoma, Mantle-Cell; Lymphoma, Large-Cell, Anaplastic; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Epothilones; Epothilone B
• Other Study ID Numbers: NCI-2009-00031 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM62201 (U.S. NIH Grant/Contract); N01CM62202 (U.S. NIH Grant/Contract); P30CA014599 (U.S. NIH Grant/Contract); NCI-5913; UCCRC-NCI-5913; CDR0000285683; UCCRC-11965B; 11965B (Other Identifier: University of Chicago); 5913 (CTEP)