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.
Studieoversigt
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Delaware
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Lewes, Delaware, Forenede Stater, 19958
- Tunnell Cancer Center at Beebe Medical Center
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Newark, Delaware, Forenede Stater, 19713
- CCOP - Christiana Care Health Services
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Illinois
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Chicago, Illinois, Forenede Stater, 60637-1470
- University of Chicago Cancer Research Center
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Chicago, Illinois, Forenede Stater, 60612-7243
- University of Illinois Cancer Center
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Maryland
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Baltimore, Maryland, Forenede Stater, 21201
- Greenebaum Cancer Center at University of Maryland Medical Center
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Elkton, Maryland, Forenede Stater, 21921
- Union Hospital Cancer Program at Union Hospital
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Mayo Clinic Cancer Center
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New Jersey
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Voorhees, New Jersey, Forenede Stater, 08043
- Cancer Institute of New Jersey at Cooper - Voorhees
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New York
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New York, New York, Forenede Stater, 10021
- New York Weill Cornell Cancer Center at Cornell University
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North Carolina
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Durham, North Carolina, Forenede Stater, 27710
- Duke Comprehensive Cancer Center
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Winston-Salem, North Carolina, Forenede Stater, 27157-1096
- Wake Forest University Comprehensive Cancer Center
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Ohio
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Columbus, Ohio, Forenede Stater, 43210-1240
- Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19111-2497
- Fox Chase Cancer Center - Philadelphia
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Philadelphia, Pennsylvania, Forenede Stater, 19104-4283
- Abramson Cancer Center of the University of Pennsylvania
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Pittsburgh, Pennsylvania, Forenede Stater, 15224-1791
- Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
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Virginia
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Richmond, Virginia, Forenede Stater, 23298-0037
- Virginia Commonwealth University Massey Cancer Center
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
- Histologic documentation of chronic GvHD following allogeneic HCT or donor lymphocyte infusion.
- Patients may have progressive, quiescent, or de novo onset chronic GvHD.
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
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.
- Patients with established chronic GvHD not improving or progressing on other immunosuppressive agents are also eligible if steroid refractoriness has been established previously.
- Age ≥ 18 years
- Performance Status 0-3
- Patients on mechanical ventilation are excluded.
- No active infection. Patients with active infection requiring antibiotic therapy are not eligible until infection is controlled.
- No HIV infection. Patients with HIV infection are excluded because of safety concerns in this patient population.
- 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).
Required Initial Laboratory Values:
- Calc. Creatinine Clearance ≥ 30 mL/min/1.73 m^2
- ANC > 1000/μL
- Platelets > 50,000/μL without transfusion
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Støttende pleje
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Pentostatin
treatment of pts with refractory graft vs host disease
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4 mg/sq m IV infusion over 20-30 min q 2 weeks
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Response Rate
Tidsramme: 3 months
|
Percentage of participants who had a complete or partial response defined by the Hopkins scoring system. A complete response is defined as the disappearance of signs and symptoms of chronic GVHD in all involved systems that is sustained for at lest 4 weeks. A partial response is an improvement by 2 or more points in at least one system score, which is sustained for at least 4 weeks, with no signs of worsening in others. |
3 months
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Grade 3 or Higher Non-hematologic Adverse Events
Tidsramme: Duration of treatment (up to 5 years)
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Number of participants experiencing a grade 3, 4 or 5 clinically significant non-hematologic adverse events, at least possibly related to treatment.
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Duration of treatment (up to 5 years)
|
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Overall Survival At 1 Year
Tidsramme: 1 year
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Percentage of patients who were alive at 1 year.
|
1 year
|
|
Overall Survival At 2 Years
Tidsramme: 2 year
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Percentage of patients who were alive at 2 years.
|
2 year
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Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Pharmacokinetics Association Between Exposure and Response At 3 Months
Tidsramme: 3 months
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The individual PK parameters will be derived by using a noncompartmental analysis of the plasma-concentration-time data
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3 months
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Samarbejdspartnere og efterforskere
Samarbejdspartnere
Efterforskere
- Studiestol: Sherif S. Farag, MD, PhD, Ohio State University
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- CALGB-100101
- U10CA031946 (U.S. NIH-bevilling/kontrakt)
- CDR0000341678 (Registry Identifier: NCI Physician Data Query)
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