Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After MUD BMT
Primary Purpose
Leukemia, Lymphoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pentostatin
Tacrolimus
Methotrexate
Sponsored by

About this trial
This is an interventional treatment trial for Leukemia focused on measuring Graft-Versus-Host Disease, GVHD Prevention, Hodgkin's Disease, Leukemia, Lymphoma, Methotrexate, Tacrolimus, Pentostatin
Eligibility Criteria
Inclusion Criteria:
- Patients receiving allogeneic hematopoietic transplants from an unrelated donor or one antigen mismatched related donors.
- Patients with AML, ALL, Hodgkin's disease, MDS (including CMML), CML in late chronic or accelerated phase or in blast crisis, and lymphoma in first or later relapses.
- Patients must have bilirubin < 1.5 mg/dL, DLCO > 50% predicted, LVEF > 45% and performance status 0 or 1.
- Candidates must have a creatinine level < 1.5 mg/dL or a calculated creatinine clearance > 60 ml/min.
Exclusion Criteria:
- HIV seropositivity
- Uncontrolled infection
- Pregnancy
- Candidates should not have received chemotherapy other than hydroxyurea or Gleevec for at least 3 weeks prior to treatment. Maintenance therapy with oral chemotherapy is acceptable. Treatment day is defined as transplant day +8, which is the date of first dose of pentostatin.
- Diagnosis of myelofibrosis.
Sites / Locations
- U.T.M.D. Anderson Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
No Pentostatin
Pentostatin 0.5
Pentostatin 1
Pentostatin 1.5
Pentostatin 2
Arm Description
Group 1: No Pentostatin
Group 2: Pentostatin 0.5 mg/m^2
Group 3: Pentostatin 1 mg/m^2
Group 4: Pentostatin 1.5 mg/m^2
Group 5: Pentostatin 2 mg/m^2
Outcomes
Primary Outcome Measures
Number of Patients Without GVHD at 100 Days
The primary efficacy endpoint of escalating doses Pentostatin with Tacrolimus + Methotrexate is success, defined to be that the patient is alive, engrafted, and without acute graft-versus-host disease (GVHD) at 100 days.
Secondary Outcome Measures
Full Information
NCT ID
NCT00506922
First Posted
July 20, 2007
Last Updated
April 6, 2015
Sponsor
M.D. Anderson Cancer Center
Collaborators
Astex Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00506922
Brief Title
Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After MUD BMT
Official Title
Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After Matched-Unrelated Donor Blood and Marrow Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
September 2000 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
Astex Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Primary Objective:
1. To determine efficacy of escalating doses of pentostatin in combination with tacrolimus and methotrexate for the prevention of acute graft-versus-host disease (GVHD) in the context of unrelated donor and one antigen mismatched related donor transplantation.
Secondary Objectives:
To determine safety of escalating doses of pentostatin in combination with tacrolimus and methotrexate.
To reduce the incidence of acute GVHD following transplants with unrelated donor to 40%.
To document blood levels of tacrolimus when combined with pentostatin.
Detailed Description
During the study, patients will have blood, urine, bone marrow, and X-ray exams done. These exams are done to monitor the results of the transplantation. Blood tests will be done daily while patients are hospitalized.
Patients in this study will receive chemotherapy and/or radiation to treat their malignancy and prevent graft rejection. This is given before the infusion of donor cells.
Patients with myeloid leukemias may receive busulfan by vein (IV) for 4 days and cyclophosphamide by vein for 2 days.
Patients with lymphoid malignancies may receive thiotepa by vein in one dose, cyclophosphamide by vein for 2 days, and irradiation for 4 days.
Other chemotherapy treatments may be used before donor cell infusion.
IV injections will be given through a previously inserted catheter that extends into the vena cava (a large chest vein).
Patients will be randomly picked (as in the toss of a coin) to receive one of five different treatments. This is done to learn the benefit of pentostatin treatment and the appropriate dose. Four of the treatments will use different dose schedules of pentostatin. The fifth treatment group will receive no pentostatin at all. All patients receive tacrolimus and methotrexate.
Pentostatin will be given by vein in 4 doses during the first month after transplant. Tacrolimus (FK506) will be given by vein or mouth for 6 months. Methotrexate will be given by vein for 3 doses in the first week after transplant.
Patients will receive blood and platelet transfusions after the transplant. The number of transfusions will depend on how quickly the blood cell counts return to a normal range.
Patients will remain in the hospital for about 4-6 weeks and in the Houston area for 100 days after the transplant.
This is an investigational study. All of the study drugs are commercially available. Pentostatin will not be used for GVHD prevention outside of this study. A total of 150 patients will take part in this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
Graft-Versus-Host Disease, GVHD Prevention, Hodgkin's Disease, Leukemia, Lymphoma, Methotrexate, Tacrolimus, Pentostatin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
150 (Actual)
8. Arms, Groups, and Interventions
Arm Title
No Pentostatin
Arm Type
Experimental
Arm Description
Group 1: No Pentostatin
Arm Title
Pentostatin 0.5
Arm Type
Experimental
Arm Description
Group 2: Pentostatin 0.5 mg/m^2
Arm Title
Pentostatin 1
Arm Type
Experimental
Arm Description
Group 3: Pentostatin 1 mg/m^2
Arm Title
Pentostatin 1.5
Arm Type
Experimental
Arm Description
Group 4: Pentostatin 1.5 mg/m^2
Arm Title
Pentostatin 2
Arm Type
Experimental
Arm Description
Group 5: Pentostatin 2 mg/m^2
Intervention Type
Drug
Intervention Name(s)
Pentostatin
Other Intervention Name(s)
Nipent, Deoxycoformycin, DCF
Intervention Description
Given intravenously on days +8, +15, +22 and +30 post transplant:
Group 2 - Pentostatin 0.5 mg/m^2
Group 3 - Pentostatin 1 mg/m^2
Group 4 - Pentostatin 1.5 mg/m^2
Group 5 - Pentostatin 2 mg/m^2
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
Prograf
Intervention Description
Given intravenously from day -2, and will be switched to oral dosing when tolerated.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Primary Outcome Measure Information:
Title
Number of Patients Without GVHD at 100 Days
Description
The primary efficacy endpoint of escalating doses Pentostatin with Tacrolimus + Methotrexate is success, defined to be that the patient is alive, engrafted, and without acute graft-versus-host disease (GVHD) at 100 days.
Time Frame
100 days
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients receiving allogeneic hematopoietic transplants from an unrelated donor or one antigen mismatched related donors.
Patients with AML, ALL, Hodgkin's disease, MDS (including CMML), CML in late chronic or accelerated phase or in blast crisis, and lymphoma in first or later relapses.
Patients must have bilirubin < 1.5 mg/dL, DLCO > 50% predicted, LVEF > 45% and performance status 0 or 1.
Candidates must have a creatinine level < 1.5 mg/dL or a calculated creatinine clearance > 60 ml/min.
Exclusion Criteria:
HIV seropositivity
Uncontrolled infection
Pregnancy
Candidates should not have received chemotherapy other than hydroxyurea or Gleevec for at least 3 weeks prior to treatment. Maintenance therapy with oral chemotherapy is acceptable. Treatment day is defined as transplant day +8, which is the date of first dose of pentostatin.
Diagnosis of myelofibrosis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcos de Lima, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
U.T.M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
19654407
Citation
Parmar S, Del Lima M, Zou Y, Patah PA, Liu P, Cano P, Rondon G, Pesoa S, de Padua Silva L, Qazilbash MH, Hosing C, Popat U, Kebriaei P, Shpall EJ, Giralt S, Champlin RE, Stastny P, Fernandez-Vina M. Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease. Blood. 2009 Oct 1;114(14):2884-7. doi: 10.1182/blood-2009-05-223172. Epub 2009 Aug 4.
Results Reference
derived
Links:
URL
http://www.mdanderson.org
Description
UT MD Anderson Cancer Center website
Learn more about this trial
Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After MUD BMT
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