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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00058019
First received: April 7, 2003
Last updated: May 7, 2014
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
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
Drug: ixabepilone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Epothilone B Analog BMS-247550 (NSC 710428) in Patients With Relapsed Aggressive Non-Hodgkin's Lymphomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective Overall Response Rate [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    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.

  • Safety and Toxicity of Ixabepilone [ Time Frame: up to 3 years ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    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.

  • Time to Progression [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 51
Study Start Date: February 2003
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00058019

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Sonali Smith University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00058019     History of Changes
Obsolete Identifiers: NCT01660269
Other Study ID Numbers: NCI-2009-00031, NCI-2009-00031, NCI-5913, UCCRC-NCI-5913, CDR0000285683, UCCRC-11965B, 11965B, 5913, P30CA014599, N01CM62202, N01CM62201
Study First Received: April 7, 2003
Results First Received: August 19, 2013
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Burkitt Lymphoma
Lymphoma
Lymphoma, Large-Cell, Anaplastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms, Experimental
Lymphoma, T-Cell
Epothilone B
Epothilones
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014