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
18 Years
64 Years
Both
Lymphoma
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Luis Fayad, MD
Investigator Role:
Study Chair
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000269140
NCT ID:
NCT00053105
Start Date:
February 2002
Completion Date:
Related Keywords:
- Lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- recurrent adult immunoblastic large cell lymphoma
- Lymphoma
- Lymphoma, Non-Hodgkin
Name | Location |
|---|---|
| University of Texas - MD Anderson Cancer Center | Houston, Texas 77030-4009 |
| Ireland Cancer Center | Cleveland, Ohio 44106-5065 |
| USC/Norris Comprehensive Cancer Center and Hospital | Los Angeles, California 90033-0804 |
| Marlene and Stewart Greenebaum Cancer Center, University of Maryland | Baltimore, Maryland 21201-1595 |
| Arizona Clinical Research Center | Tucson, Arizona 85712 |
| Highlands Oncology Group | Springdale, Arkansas 72764 |
| Boston Baskin Cancer Group, University Tennessee | Memphis, Tennessee 38104 |
