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

NCT00074035 | Completed Phase 2 Results

• 3 other identifiers: CALGB-100101U10CA031946CDR0000341678
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 16

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.

Conditions

Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• Response Rate

  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

Secondary Outcomes (3)

• Grade 3 or Higher Non-hematologic Adverse Events

  Duration of treatment (up to 5 years)

• Overall Survival At 1 Year

  1 year

• Overall Survival At 2 Years

  2 year

Other Outcomes (1)

• Pharmacokinetics Association Between Exposure and Response At 3 Months

  3 months

Study Arms (1)

Pentostatin

EXPERIMENTAL

treatment of pts with refractory graft vs host disease

Drug: pentostatin

Interventions

pentostatin DRUG

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

Pentostatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (16)

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612-7243, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Union Hospital Cancer Program at Union Hospital

Elkton, Maryland, 21921, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

New York Weill Cornell Cancer Center at Cornell University

New York, New York, 10021, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

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

Columbus, Ohio, 43210-1240, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224-1791, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Pentostatin

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Sherif S. Farag, M.D., Ph.D.
• Organization: The Ohio State University Medical Center

farag-1@medctr.osu.edu

Study Officials

• Sherif S. Farag, MD, PhD

  Ohio State University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2003
• First Posted: December 11, 2003
• Study Start: December 1, 2003
• Primary Completion: August 1, 2008
• Study Completion: November 1, 2014
• Last Updated: November 3, 2021
• Results First Posted: March 15, 2017

Record last verified: 2021-10

Locations

US (16)