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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00074035
First received: December 10, 2003
Last updated: June 23, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Graft Versus Host Disease
Drug: pentostatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Phase II Trial Of Intravenous Pentostatin For The Treatment Of Patients With Refractory Chronic Graft-Versus-Host Disease

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Response rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Both complete and partial response will be assessed


Secondary Outcome Measures:
  • Toxicity [ Time Frame: During tx, then at relapse or progression ] [ Designated as safety issue: Yes ]
  • Survival [ Time Frame: At 1 year and 2 years post treatment initiation ] [ Designated as safety issue: No ]
  • Pharmacokinetics [ Time Frame: At initiation of Tx and at 3 months ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: December 2003
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pentostatin
treatment of pts with refractory graft vs host disease
Drug: pentostatin
4 mg/sq m IV infusion over 20-30 min q 2 weeks

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  1. Histologic documentation of chronic GvHD following allogeneic HCT or donor lymphocyte infusion.
  2. Patients may have progressive, quiescent, or de novo onset chronic GvHD.
  3. Patients with extensive stage chronic GvHD requiring systemic immunosuppressive therapy are eligible. Patients with limited stage disease are excluded. Extensive stage is defined according to Seattle criteria (9) as either:

    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074035

Locations
United States, Delaware
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, United States, 19958
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
University of Illinois Cancer Center
Chicago, Illinois, United States, 60612-7243
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Union Hospital Cancer Program at Union Hospital
Elkton MD, Maryland, United States, 21921
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, New Jersey
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
United States, New York
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210-1240
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224-1791
United States, Virginia
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Sherif S. Farag, MD, PhD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00074035     History of Changes
Other Study ID Numbers: CALGB-100101, U10CA031946, CDR0000341678
Study First Received: December 10, 2003
Last Updated: June 23, 2015
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Pentostatin
Adenosine Deaminase Inhibitors
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 01, 2015