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

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

• Status: Unknown
• Conditions: Lymphoma
• Intervention / Treatment: Drug: cytarabine; Drug: methylprednisolone; Drug: cisplatin; Drug: pixantrone dimaleate

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

Study Locations

• United States
  • 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

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

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

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

Study record dates

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

Terms related to this study

• Keywords: recurrent grade 3 follicular lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Cytarabine; Pixantrone
• Other Study ID Numbers: CDR0000269140; THERADEX-AZA-I-05; NOVUSPHARMA-AZA-I-05; NOVUSPHARMA-AZA-1401; CWRU-050213J