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

December 10, 2003
June 23, 2015
December 2003
August 2008   (final data collection date for primary outcome measure)
Response rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Both complete and partial response will be assessed
Not Provided
Complete list of historical versions of study NCT00074035 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Pentostatin in Treating Patients With Refractory Chronic Graft-Versus-Host Disease
A Phase II Trial Of Intravenous Pentostatin For The Treatment Of Patients With Refractory Chronic Graft-Versus-Host Disease

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Graft Versus Host Disease
Drug: pentostatin
4 mg/sq m IV infusion over 20-30 min q 2 weeks
Experimental: Pentostatin
treatment of pts with refractory graft vs host disease
Intervention: Drug: pentostatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
39
Not Provided
August 2008   (final data collection date for primary outcome measure)
  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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00074035
CALGB-100101, U10CA031946, CDR0000341678
No
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Sherif S. Farag, MD, PhD Ohio State University
Alliance for Clinical Trials in Oncology
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP