RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with rituximab may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining pixantrone, fludarabine, and dexamethasone with rituximab in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
grade 1 follicular lymphoma grade 2 follicular lymphoma indolent, adult non-Hodgkin's lymphoma marginal zone lymphoma Small Lymphocytic Lymphoma	Drug: dexamethasone  Drug: fludarabine  Drug: pixantrone  Drug: rituximab  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose and recommended dose of pixantrone when administered with fludarabine, dexamethasone, and rituximab in patients with relapsed or refractory indolent non-Hodgkin's lymphoma.
• Determine the safety of this regimen in these patients.
• Determine the dose-limiting toxic effects of this regimen in these patients and the relationship between toxicity and systemic exposure.
• Evaluate the efficacy of this regimen in these patients.
• Evaluate the pharmacokinetics of pixantrone in these patients.

OUTLINE: This is a multicenter, dose-escalation study of pixantrone.

Patients receive oral dexamethasone on days 1-5, fludarabine IV over 30 minutes on days 2-4, and pixantrone IV over 1 hour on day 2. Patients also receive rituximab IV on day 1 for courses 1-6. Treatment repeats every 28 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 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the recommended dose, which is the dose preceding the MTD.

Patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 3-40 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed relapsed or refractory indolent non-Hodgkin's lymphoma including the following:
• Follicular center cell lymphomas grade I (formerly known as follicular small cleaved)
• Follicular center cell lymphomas grade II (formerly known as follicular mixed)
• Small lymphocytic lymphoma
• Lymphoplasmacytoid lymphoma (also known as immunocytoma and Waldenstrom's macroglobulinemia)
• Marginal zone lymphomas:
• MALT lymphomas
• Monocytoid B-cell lymphomas
• Splenic marginal zone lymphomas
• Must have received 1-3 prior chemotherapy regimens

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• WHO 0-1

Life expectancy

• At least 3 months

Hematopoietic

• Neutrophil count ≥ 1,500/mm^3*
• Platelet count ≥ 100,000/mm^3* NOTE: *Lower values may be accepted if due to bone marrow involvement

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)**
• Alkaline phosphatase ≤ 2 times ULN**
• AST or ALT ≤ 2 times ULN**
• No history or clinical symptoms of hepatitis B or C NOTE: **Higher values may be accepted if due to liver involvement

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• LVEF ≥ 50% by MUGA
• No myocardial infarction within the past 6 months
• No clinically significant cardiovascular abnormalities
• No New York Heart Association class II-IV heart disease
• No severe arrhythmia
• No uncontrolled hypertension

Other

• Not pregnant or nursing
• Negative pregnant test
• Fertile patients must use effective contraception during and for 6 months after study participation
• No prior history or clinical symptoms of HIV
• No concurrent uncontrolled infection (NCI CTC grade 3-4)
• No condition that would place the patient at undue risk or interfere with study results
• No known type I hypersensitivity or anaphylactic reactions to murine proteins or any component of rituximab
• No clinically significant neurological abnormality

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior rituximab unless there was a complete or partial response
• At least 3 months since prior radioimmunotherapy

Chemotherapy

• See Disease Characteristics
• More than 12 months since prior treatment with fludarabine and responded to treatment (e.g., complete or partial response)
• No prior cumulative dose of doxorubicin equivalent greater than 450 mg/m^2
• At least 4 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Biologic therapy
• At least 4 weeks since prior radiotherapy

Surgery

• At least 4 weeks since prior major thoracic and/or abdominal therapy and recovered

Other

• Recovered from prior therapy
• At least 30 days since prior investigational drugs
• No other concurrent investigational drugs

Arizona
      Arizona Clinical Research Center, Incorporated, Tucson,  Arizona,  85715,  United States; Recruiting
Illinois
      Rush Cancer Institute at Rush University Medical Center, Chicago,  Illinois,  60612,  United States; Recruiting
Maryland
      Cancer Center at Greater Baltimore Medical Center, Baltimore,  Maryland,  21204-6881,  United States; Recruiting
New Mexico
      New Mexico Cancer Center, Albuquerque,  New Mexico,  87109,  United States; Recruiting
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030,  United States; Recruiting

Study chairs or principal investigators

Luis Fayad, MD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000269139; THERADEX-AZA-I-06; NOVUSPHARMA-AZA-I-06; NCT00057772
Record last reviewed:  April 2004
Last Updated:  February 7, 2005
Record first received:  April 7, 2003
ClinicalTrials.gov Identifier:  NCT00057772
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08