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

NCT ID: NCT00074035

Last Updated: 2021-11-03

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

39 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-12-31

Study Completion Date

2014-11-01

Brief Summary

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RATIONALE: Pentostatin may be effective in treating chronic graft-versus-host disease by stopping the immune system from rejecting donor stem cells or donor white blood cells.

PURPOSE: This phase II trial is studying how well pentostatin works in treating patients with chronic graft-versus-host disease that is refractory (not responsive) to treatment with steroids.

Detailed Description

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OBJECTIVES:

Primary

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

Secondary

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

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.

PROJECTED ACCRUAL: Approximately 37 patients will be accrued for this study.

Conditions

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Graft Versus Host Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Pentostatin

treatment of pts with refractory graft vs host disease

Group Type EXPERIMENTAL

pentostatin

Intervention Type DRUG

4 mg/sq m IV infusion over 20-30 min q 2 weeks

Interventions

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pentostatin

4 mg/sq m IV infusion over 20-30 min q 2 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Generalized skin involvement or
* Limited skin involvement or hepatic involvement with any one of the following:

* Liver histology showing chronic progressive hepatitis, bridging necrosis or cirrhosis
* Eye involvement (Schirmer's test with \< 5 mm wetting)
* Involvement of minor salivary glands or oral mucosa
* Involvement of any other organ
4. Patients must have failed treatment with, or experience progression after, prior corticosteroids for extensive stage chronic GvHD, as defined below.

4.1 Patients will be considered to have failed corticosteroids if they have any one of the following criteria:
* Progressive disease or less than a minor response in any organ system despite 2 weeks on corticosteroid treatment at least 1 mg/kg methylprednisolone or equivalent.
* Failure to achieve at least a minor response after at least 4 weeks of treatment with a dose of ≥ 0.5 mg/kg methylprednisolone or equivalent.
* Achievement of less than a partial response at 8 weeks of corticosteroid treatment despite use of a dose ≥ 0.5 mg/kg methylprednisolone or equivalent.
* Requirement of ≥ 0.5 mg/kg methylprednisolone or equivalent to maintain a partial response or better at 12 weeks of corticosteroid treatment.
* Requirement of \> 10 mg/kg methylprednisolone or equivalent to maintain a partial response or better at 18 weeks of corticosteroid treatment.

4.2 Patients with progression of extensive stage chronic GvHD after a prior history of treatment with at least 18 weeks of corticosteroids, now requiring the reintroduction of corticosteroids (\> 10 mg/day methylprednisolone or equivalent) or an additional agent (including photopheresis, PUVA) for treatment.
5. Patients with established chronic GvHD not improving or progressing on other immunosuppressive agents are also eligible if steroid refractoriness has been established previously.
6. Age ≥ 18 years
7. Performance Status 0-3
8. Patients on mechanical ventilation are excluded.
9. No active infection. Patients with active infection requiring antibiotic therapy are not eligible until infection is controlled.
10. No HIV infection. Patients with HIV infection are excluded because of safety concerns in this patient population.
11. Non-pregnant and non-nursing. Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial (although it is unlikely that successful pregnancy will occur in patients with chronic GvHD). Appropriate methods of birth control include oral contraceptives, implantable hormonal contraceptives (Norplant®), or double barrier method (diaphragm plus condom).
12. Required Initial Laboratory Values:

* Calc. Creatinine Clearance ≥ 30 mL/min/1.73 m\^2
* ANC \> 1000/μL
* Platelets \> 50,000/μL without transfusion
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sherif S. Farag, MD, PhD

Role: STUDY_CHAIR

Ohio State University

Locations

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Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

Site Status

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Site Status

University of Illinois Cancer Center

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Union Hospital Cancer Program at Union Hospital

Elkton, Maryland, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, United States

Site Status

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000341678

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-100101

Identifier Type: -

Identifier Source: org_study_id