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

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over Pharmaceutical / Industry THERADEX-AZA-II-02 CWRU-NOVU-1403, SUNY-HSC-4849, NOVUSPHARMA-AZA-II-02, NCT00069966

Objectives

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

Entry Criteria

Disease Characteristics:

• Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL)
  • Any stage, with or without B symptoms
  • The following subtypes are eligible:
    • 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, CR_u, 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

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/m²
• No prior single or cumulative dose of doxorubicin greater than 450 mg/m²

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

Patient Characteristics:

Age

• 18 and over

Performance status

• WHO 0-1

Life expectancy

• At least 3 months

Hematopoietic

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

 [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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Theradex Systems, Incorporated

Julie Vose, MD, Protocol chair		Ph: 402-559-3848 Email: jmvose@unmc.edu

Registry Information
Official Title		A Phase II Trial of BBR 2778 in Combination with Cytarabine, Methylprednisolone and Cisplatin (BSHAP) as Salvage in Patients with Relapsed Aggressive Non-Hodgkin’s Lymphoma
Trial Start Date		2003-04-21
Registered in ClinicalTrials.gov		NCT00069966
Date Submitted to PDQ		2003-06-27
Information Last Verified		2004-11-22
NCI Grant/Contract Number		P30-CA43703