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

• ClinicalTrials.gov Identifier: NCT00053105
• Recruitment Status: Unknown
• First Posted: January 28, 2003
• Last Update Posted: July 7, 2009
• Sponsor: Theradex
• Information provided by: National Cancer Institute (NCI)

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 (Clinical Trial)
• 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: February 2002

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Arizona Clinical Research Center

Tucson, Arizona, United States, 85712

United States, Arkansas

Highlands Oncology Group

Springdale, Arkansas, United States, 72764

United States, California

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States, 90033-0800

United States, Maryland

Marlene and Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States, 21201

United States, Ohio

Ireland Cancer Center

Cleveland, Ohio, United States, 44106-5055

United States, Tennessee

Boston Baskin Cancer Group, University Tennessee

Memphis, Tennessee, United States, 38104

United States, Texas

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Theradex

Investigators

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

More Information

• ClinicalTrials.gov Identifier: NCT00053105
• Other Study ID Numbers: CDR0000269140; THERADEX-AZA-I-05; NOVUSPHARMA-AZA-I-05; NOVUSPHARMA-AZA-1401; CWRU-050213J
• First Posted: January 28, 2003
• Last Update Posted: July 7, 2009
• Last Verified: March 2003

Keywords provided by National Cancer Institute (NCI):

recurrent adult diffuse large cell lymphoma; recurrent grade 3 follicular lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent adult immunoblastic large cell lymphoma

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cytarabine; Methylprednisolone; Pixantrone; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents