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

July 4, 2009 updated by: Theradex

A Phase I Trial of BBR 2778 in Combination With Cytarabine, Methylprednisolone and Cisplatin in the Treatment of Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effect of combination chemotherapy on the body when treating patients who have relapsed or refractory aggressive non-Hodgkin's lymphoma.

Study Overview

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose and recommended dose of pixantrone when administered with cytarabine, methylprednisolone, and cisplatin in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.
  • Determine the dose-limiting toxic effects of this regimen in these patients.
  • Determine the relationship between toxicity and systemic exposure to this regimen in these patients.
  • Determine the safety of this regimen in these patients.
  • Assess the pharmacokinetics of this regimen in these patients.
  • Determine, preliminarily, the efficacy of this regimen in these patients.

OUTLINE: This is an open-label, non-randomized, multicenter, dose-escalation study of pixantrone.

Patients receive pixantrone IV over 1 hour on day 1, methylprednisolone IV over 15 minutes on days 1-5, cisplatin IV over 30 minutes on days 1-4, and cytarabine IV over 2 hours on day 5. Treatment repeats every 21 days for at least 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of pixantrone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the recommended dose, which is defined as the dose preceding the MTD.

Patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 3-30 patients will be accrued for this study.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Arizona
      • Tucson, Arizona, United States, 85712
        • Arizona Clinical Research Center
    • Arkansas
      • Springdale, Arkansas, United States, 72764
        • Highlands Oncology Group
    • California
      • Los Angeles, California, United States, 90033-0800
        • USC/Norris Comprehensive Cancer Center and Hospital
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Marlene and Stewart Greenebaum Cancer Center, University of Maryland
    • Ohio
      • Cleveland, Ohio, United States, 44106-5055
        • Ireland Cancer Center
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Boston Baskin Cancer Group, University Tennessee
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas - MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) including the following:

    • Diffuse large B-cell lymphoma
    • Transformed NHL
    • Follicular large cell lymphoma
    • Peripheral T-cell lymphoma
    • Unclassified aggressive histology (immunoblastic lymphoma)
  • Must have received 1 to 3 prior chemotherapy treatment regimens (may include doxorubicin up to a cumulative dose of no greater than 450 mg/m^2)
  • No Burkitt's lymphoma, lymphoblastic lymphoma, or mantle cell lymphoma

PATIENT CHARACTERISTICS:

Age

  • 18 to 64

Performance status

  • WHO 0-1

Life expectancy

  • At least 3 months

Hematopoietic

  • Neutrophil count at least 1,500/mm^3*
  • Platelet count at least 100,000/mm^3* NOTE: *Lower values may be accepted if evidence of bone marrow involvement

Hepatic

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)**
  • Alkaline phosphatase no greater than 2 times ULN**
  • AST or ALT no greater than 2 times ULN**
  • No history or clinical symptoms of hepatitis B or C virus NOTE: **Higher values may be accepted if evidence of liver involvement

Renal

  • Creatinine no greater than 1.5 mg/dL

Cardiovascular

  • LVEF at least 50% by MUGA
  • No clinically significant cardiovascular abnormalities
  • No New York Heart Association class II-IV heart disease
  • No myocardial infarction within the past 6 months
  • No severe arrhythmia
  • No uncontrolled hypertension

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 6 months after study
  • No history or clinical symptoms of HIV
  • No clinically significant neurological abnormalities
  • No serious uncontrolled infection (NCI CTC grade 3-4)
  • No condition that would place the patient at undue risk or interfere with the study results

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • At least 3 months since prior radioimmunotherapy

Chemotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy
  • At least 1 year since prior platinum or cytarabine (unless complete response to treatment)
  • At least 2 years since prior fludarabine or nitrosoureas
  • No prior cumulative cisplatin greater than 600 mg/m^2

Endocrine therapy

  • Not specified

Radiotherapy

  • See Biologic therapy
  • At least 4 weeks since prior radiotherapy
  • No prior radiotherapy to the whole pelvis

Surgery

  • At least 1 week since prior minor surgery and recovered
  • At least 4 weeks since prior major thoracic and/or abdominal surgery and recovered

Other

  • At least 1 month since prior investigational drugs
  • Recovered from prior therapy
  • No other concurrent investigational drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Chair: Luis Fayad, MD, M.D. Anderson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2002

Study Registration Dates

First Submitted

January 27, 2003

First Submitted That Met QC Criteria

January 27, 2003

First Posted (Estimate)

January 28, 2003

Study Record Updates

Last Update Posted (Estimate)

July 7, 2009

Last Update Submitted That Met QC Criteria

July 4, 2009

Last Verified

March 1, 2003

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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