Pixantrone, Cytarabine, Methylprednisolone, and Cisplatin in Treating Patients With Aggressive Non-Hodgkin's Lymphoma in First Relapse

NCT ID: NCT00069966

Last Updated: 2009-07-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-04-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as pixantrone, cytarabine, methylprednisolone, and cisplatin, work in 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 II trial to study the effectiveness of combination chemotherapy in treating patients who have relapsed aggressive non-Hodgkin's lymphoma.

Detailed Description

OBJECTIVES:

• Determine the antitumor activity of pixantrone, cytarabine, methylprednisolone, and cisplatin in patients with aggressive non-Hodgkin's lymphoma in first relapse.
• Determine the safety and tolerability of this regimen in these patients.
• Determine the validity and safety of this regimen as a mobilization regimen before high-dose chemotherapy with stem cell support in these patients.

OUTLINE: This is an open-label, multicenter study.

• Salvage therapy: Patients receive pixantrone IV over 1 hour on day 1; cisplatin IV over 30 minutes on days 1-4; methylprednisolone IV over 15-30 minutes on days 1-5; and cytarabine IV over 2 hours on day 5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After 2 courses of salvage therapy, patients are re-evaluated and treated as follows:

• Complete response (CR) or partial response (PR): Patients with a CR or PR who are suitable candidates for autologous stem cell transplantation (ASCT) proceed to mobilization therapy, high-dose chemotherapy, and ASCT. Patients with a CR or PR who are unsuitable candidates for ASCT continue to receive salvage therapy for up to 6 courses in the absence of disease progression or unacceptable toxicity.
• Stable disease: Patients with stable disease continue to receive salvage therapy for up to 6 courses. Patients who have a CR or PR after 3-4 courses of salvage therapy and who are suitable candidates for ASCT proceed to mobilization therapy, high-dose chemotherapy, and ASCT off study at the investigator's discretion.

• Mobilization therapy (optional regimen; regimen used for mobilization is at the investigator's discretion): Patients receive rituximab* IV on days 1 and 7; pixantrone IV over 1 hour on day 2; cisplatin IV over 30 minutes on days 2-5; cytarabine IV over 2 hours on day 6; and methylprednisolone IV over 15-30 minutes on days 2-6. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 7 and continuing until blood counts recover. Patients receive 1 or more courses of mobilization therapy during which stem cells are harvested. Patients then proceed to high-dose chemotherapy and subsequent re-infusion of harvested stem cells.

NOTE: *If this mobilization regimen is used, patients with T-cell lymphoma do not receive rituximab

• High-dose chemotherapy and ASCT: Patients receive high-dose chemotherapy and ASCT per institutional standard practice.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Conditions

Lymphoma

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

filgrastim

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

methylprednisolone

Intervention Type: DRUG

pixantrone dimaleate

Intervention Type: DRUG

autologous bone marrow transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Diffuse large cell (B and T cell types)
• Anaplastic large cell
• Diffuse mixed cell
• Immunoblastic large cell
• Follicular large cell
• Transformed follicular NHL
• Diffuse aggressive not otherwise classified
• Burkitt-like lymphoma
• Bone marrow positive or negative
• At least 1 measurable lesion

• Patients with bone marrow as the only site of disease are eligible without a measurable lesion
• No more than 1 episode of progressive disease, occurring after a response (complete response [CR], complete response unconfirmed [CR_u], or partial response [PR]) to prior chemotherapy* NOTE: *Patients with less than a CR, CRu, or PR and no progression, but who are good candidates for high-dose chemotherapy with stem cell support may be eligible (will be decided on an individual basis)
• No chemotherapy-refractory disease, defined as follows:

• Stable or progressive disease documented at restaging immediately after the completion of induction therapy
• No lymphoblastic lymphoma, or mantle cell lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 and over

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 clearly due to bone marrow involvement by lymphoma

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)*
• AST or ALT no greater than 2.0 times ULN*
• Alkaline phosphatase no greater than 2.0 times ULN*
• No history or clinical symptoms of hepatitis B or hepatitis C virus

• Patients with seropositivity due to prior vaccination for hepatitis B are eligible NOTE: *Higher values may be accepted if clearly due to liver involvement by lymphoma

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 grade II-IV cardiovascular disease
• No myocardial infarction within the past 6 months
• No severe cardiac arrhythmia
• No uncontrolled hypertension

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation
• HIV negative
• No clinically significant neurological abnormalities
• No condition that would preclude study safety or interfere with study results
• No concurrent serious uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior rituximab immediately after the first chemotherapy regimen allowed

Chemotherapy

• See Disease Characteristics
• See Biologic therapy
• At least 6 months since prior anthracycline therapy (e.g., cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])
• More than 2 years since prior fludarabine
• More than 2 years since prior nitrosoureas
• More than 1 year since prior platinum-based chemotherapy or cytarabine, unless a CR or CR_u was achieved
• No prior cumulative dose of cisplatin greater than 600 mg/m^2
• No prior single or cumulative dose of doxorubicin greater than 450 mg/m^2

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the whole pelvis
• No prior radioimmunotherapy

Surgery

• More than 4 weeks since prior major thoracic and/or abdominal surgery
• At least 1 week since prior minor surgery

Other

• Recovered from prior therapy

• Alopecia allowed
• Grade 1 peripheral neuropathy allowed
• More than 30 days since prior participation in another investigational drug study
• No other concurrent investigational drugs

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Theradex

INDUSTRY

Sponsor Role: lead

Principal Investigators

Julie M. Vose, MD

Role: STUDY_CHAIR

University of Nebraska

Locations

Arizona Oncology Associates - Craycroft Road Offices

Tucson, Arizona, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Rocky Mountain Cancer Centers - Colorado Springs

Colorado Springs, Colorado, United States

Rocky Mountain Cancer Centers - Denver Midtown

Denver, Colorado, United States

Delaware Clinical & Laboratory Physicians

Newark, Delaware, United States

Pasco, Hernando Oncology Associates, P.A.

New Port Richey, Florida, United States

Hematology-Oncology Associates of Illinois

Chicago, Illinois, United States

Markey Cancer Center at University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

Louisiana State University Health Sciences Center - Shreveport

Shreveport, Louisiana, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

North Shore University Hospital

Manhasset, New York, United States

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Piedmont Hematology-Oncology Associates

Winston-Salem, North Carolina, United States

Gabrail Cancer Center - Canton Office

Canton, Ohio, United States

Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University

Cleveland, Ohio, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Cancer Care Associates-West

Oklahoma City, Oklahoma, United States

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, United States

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Cancer Centers of the Carolinas - Eastside

Greenville, South Carolina, United States

Baylor University Medical Center

Dallas, Texas, United States

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Fairfax Northern Virginia Hematology Oncology, P.C. - Fairfax

Fairfax, Virginia, United States

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Hospital Auxilio Mutuo

Hato Rey, , Puerto Rico

Countries

United States; Puerto Rico

Other Identifiers

THERADEX-AZA-II-02

Identifier Type: -

Identifier Source: secondary_id

CWRU-NOVU-1403

Identifier Type: -

Identifier Source: secondary_id

SUNY-HSC-4849

Identifier Type: -

Identifier Source: secondary_id

NOVUSPHARMA-AZA-II-02

Identifier Type: -

Identifier Source: secondary_id

CDR0000316466

Identifier Type: -

Identifier Source: org_study_id