Clinical trial NCT00074035: Pentostatin in Treating Patients With Refractory Chronic Graft-Versus-Host Disease
Official title: A Phase II Trial Of Intravenous Pentostatin For The Treatment Of Patients With Refractory Chronic Graft-Versus-Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft Versus Host Disease
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-12-11
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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 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

Primary outcomes:
measure: Response Rate
timeFrame: 3 months
Secondary outcomes:
measure: Grade 3 or Higher Non-hematologic Adverse Events
timeFrame: Duration of treatment (up to 5 years)
measure: Overall Survival At 1 Year
timeFrame: 1 year
measure: Overall Survival At 2 Years
timeFrame: 2 year
Other outcomes:
measure: Pharmacokinetics Association Between Exposure and Response At 3 Months
timeFrame: 3 months
Locations:
city: Lewes
country: United States
facility: Tunnell Cancer Center at Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Elkton
country: United States
facility: Union Hospital Cancer Program at Union Hospital
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
Study officials:
affiliation: Ohio State University
name: Sherif S. Farag, MD, PhD
role: STUDY_CHAIR
References: