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

NCT ID: NCT00053105

Last Updated: 2009-07-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-02-28

Brief Summary

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.

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.

Conditions

Lymphoma

Study Design

• Primary Study Purpose: TREATMENT

Interventions

cisplatin

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

methylprednisolone

Intervention Type: DRUG

pixantrone dimaleate

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Theradex

INDUSTRY

Sponsor Role: lead

Principal Investigators

Luis Fayad, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

Arizona Clinical Research Center

Tucson, Arizona, United States

Highlands Oncology Group

Springdale, Arkansas, United States

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Marlene and Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Ireland Cancer Center

Cleveland, Ohio, United States

Boston Baskin Cancer Group, University Tennessee

Memphis, Tennessee, United States

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

THERADEX-AZA-I-05

Identifier Type: -

Identifier Source: secondary_id

NOVUSPHARMA-AZA-I-05

Identifier Type: -

Identifier Source: secondary_id

NOVUSPHARMA-AZA-1401

Identifier Type: -

Identifier Source: secondary_id

CWRU-050213J

Identifier Type: -

Identifier Source: secondary_id

CDR0000269140

Identifier Type: -

Identifier Source: org_study_id