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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00053105
• Other study ID #: CDR0000269140
• Secondary ID: THERADEX-AZA-I-0
• Status: Active, not recruiting
• Phase: Phase 1
• First received: January 27, 2003
• Last updated: July 4, 2009
• Start date: February 2002

Study information

• Verified date: March 2003
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

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 Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• cisplatin

• cytarabine

• methylprednisolone

• pixantrone dimaleate

Locations

Country	Name	City	State
United States	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Ireland Cancer Center	Cleveland	Ohio
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Boston Baskin Cancer Group, University Tennessee	Memphis	Tennessee
United States	Highlands Oncology Group	Springdale	Arkansas
United States	Arizona Clinical Research Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Theradex

Country where clinical trial is conducted

United States,