Clinical trial NCT00053105: Combination Chemotherapy in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Lymphoma
Keywords: recurrent adult diffuse large cell lymphoma
recurrent grade 3 follicular lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Baltimore
country: United States
facility: Marlene and Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Memphis
country: United States
facility: Boston Baskin Cancer Group, University Tennessee
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Luis Fayad, MD
role: STUDY_CHAIR
References: