Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	Pharmaceutical / Industry	THERADEX-AZA-I-06 NOVUSPHARMA-AZA-I-06, NCT00060684

Objectives

1. 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.
2. Determine the safety of this regimen in these patients.
3. Determine the dose-limiting toxic effects of this regimen in these patients and the relationship between toxicity and systemic exposure.
4. Evaluate the efficacy of this regimen in these patients.
5. Evaluate the pharmacokinetics of pixantrone in these patients.

Entry 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

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/m²
• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• WHO 0-1

Life expectancy

• At least 3 months

Hematopoietic

• Neutrophil count ≥ 1,500/mm³*
• Platelet count ≥ 100,000/mm³*

 [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

Expected Enrollment

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

Outcomes

Maximum tolerated dose (MTD) as measured by NCI CTC v. 2 1999 during weeks 1-8 (courses 1-2) of treatment
Recommended dose (RD) as measured by NCI CTC v. 2 1999 during weeks 1-8 (courses 1-2) of treatment

Safety profile as measured by NCI CTC v. 2 1999 weekly during study treatment, 4 weeks after completion of treatment, and every 3 months after completion of treatment
Dose-limiting toxicities (DLTs) as measured by NCI CTC v. 2 1999 during weeks 1-8 (courses 1-2) of treatment
Pharmacokinetics at 0, 0.5, 1.55, 3, 5, 24, and 48 hours after start of treatment
Objective response as assessed by standard response criteria every 8 weeks after completion of treatment
Overall survival every 3 months after completion of treatment
Progression-free survival every 3 months after completion of treatment

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.

Trial Contact Information

Trial Lead Organizations

Theradex Systems, Incorporated

Luis Fayad, MD, Protocol chair		Ph: 713-792-2860; 800-392-1611

Registry Information
Official Title		A Phase I Trial of BBR 2778 in Combination with Fludarabine, Dexamethasone and Rituximab in the Treatment of Patients with Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
Trial Start Date		2002-04-09
Registered in ClinicalTrials.gov		NCT00060684
Date Submitted to PDQ		2002-11-14
Information Last Verified		2006-10-26

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