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

Alternate Title

Pentostatin in Treating Patients With Refractory Chronic Graft-Versus-Host Disease

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Supportive care	Closed	18 and over	NCI	CALGB-100101 NCT00074035, ECOG-1010

Objectives

Primary

1. Determine the response rate in patients with refractory chronic graft-versus-host disease treated with pentostatin.

Secondary

1. Determine the time to next immunosuppressive agent (i.e., the time to progression from best response) in patients treated with this drug.
2. Determine the toxicity of this drug in these patients.
3. Determine the infection rate in patients treated with this drug.
4. Determine the pharmacokinetics of this drug in these patients.
5. Determine the changes in lymphocyte populations in patients treated with this drug.
6. Determine the survival of patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Histologically confirmed chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation or donor lymphocyte infusion
  • Progressive, quiescent, or de novo onset



• Extensive stage disease requiring systemic immunosuppressive therapy, defined according to Seattle criteria as 1 of the following:
  • Generalized skin involvement
  • Limited skin involvement or hepatic involvement with any of the following:
    • Liver histology showing chronic progressive hepatitis, bridging necrosis, or cirrhosis
    • Eye involvement (i.e., Schirmer's test with less than 5 mm wetting)
    • Involvement of minor salivary glands or oral mucosa
    • Involvement of any other organ



• Failed prior corticosteroid therapy, meeting 1 of the following criteria:
  • Progressive disease or less than a minor response in any organ system despite 2 weeks on steroid therapy at a dose of at least 1 mg/kg of methylprednisolone or equivalent
  • No response or minor response after at least 4 weeks of steroid therapy at a dose of least 0.5 mg/kg of methylprednisolone or equivalent
  • Less than a partial response after 8 weeks of steroid therapy at a dose of least 0.5 mg/kg of methylprednisolone or equivalent
  • Required a dose of least 0.5 mg/kg of methylprednisolone or equivalent after completion of at least 12 weeks of corticosteroid therapy in order to maintain a partial response or better
  • Required a dose of least 10 mg/kg of methylprednisolone or equivalent after completion of at least 18 weeks of corticosteroid therapy in order to maintain a partial response or better
  • Progressive extensive stage chronic GVHD after completion of at least 18 weeks of corticosteroid therapy and currently requiring reintroduction of corticosteroid therapy at a dose of least 10 mg/kg of methylprednisolone or equivalent OR an additional therapy (e.g., photopheresis or psoralen-ultraviolet-light [PUVA] therapy)



• Established chronic GVHD either not improving or progressing on other immunosuppressive agents allowed provided steroid refractoriness has been previously established

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• Not specified

Endocrine therapy

• See Disease Characteristics
• No concurrent corticosteroids as antiemetics

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• Concurrent continuation of other immunosuppressants administered during onset or progression of chronic GVHD is allowed
• No concurrent mechanical ventilation

Patient Characteristics:

Age

• 18 and over

Performance status

• 0-3

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count greater than 1,000/mm³
• Platelet count greater than 50,000/mm³ (without transfusion)

Hepatic

• Not specified

Renal

• Creatinine clearance at least 30 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No active infection

Expected Enrollment

Approximately 37 patients will be accrued for this study.

Outcomes

Response rate (complete and partial) at 3 months

Time to next immunosuppressive agent
Toxicity
Infection rate
Pharmacokinetics
Changes in lymphocyte populations
Survival

Outline

This is a multicenter study.

Patients receive pentostatin IV over 20-30 minutes on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients who achieve a complete response after 6 courses receive 4 additional courses. Patients who achieve a partial response, minor response, or stable disease after 6 courses may receive up to 6 additional courses.

Patients are followed every 4 weeks for 1 year, every 3 months for 2 years, and then annually for 5 years.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Sherif Farag, MD, PhD, Protocol chair		Ph: 317-274-0843; 888-600-4822 Email: ssfarag@iupui.edu
Nelson Chao, MD, Protocol co-chair		Ph: 919-668-1010 Email: chao0002@mc.duke.edu

Eastern Cooperative Oncology Group

Edward Stadtmauer, MD, Protocol chair		Ph: 215-662-7910 Email: edward.stadtmauer@uphs.upenn.edu
Hillard Lazarus, MD, Protocol co-chair		Ph: 216-844-3629 Email: hillard.lazarus@case.edu

Registry Information
Official Title		A Phase II Trial Of Intravenous Pentostatin For The Treatment Of Patients With Refractory Chronic Graft-Versus-Host Disease
Trial Start Date		2003-12-15
Trial Completion Date		2005-06-22 (estimated)
Registered in ClinicalTrials.gov		NCT00074035
Date Submitted to PDQ		2003-10-22
Information Last Verified		2008-03-20
NCI Grant/Contract Number		CA31946

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