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

Sponsor

Theradex (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00053105

Collaborator

(none)

Locations

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: cisplatin Drug: cytarabine Drug: methylprednisolone Drug: pixantrone dimaleate	Phase 1

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 Design

Study Type:

Interventional

Primary Purpose:

Treatment

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

Study Start Date :

Feb 1, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Clinical Research Center	Tucson	Arizona	United States	85712
2	Highlands Oncology Group	Springdale	Arkansas	United States	72764
3	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90033-0800
4	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
5	Ireland Cancer Center	Cleveland	Ohio	United States	44106-5055
6	Boston Baskin Cancer Group, University Tennessee	Memphis	Tennessee	United States	38104
7	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030