Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After MUD BMT

This study has been completed.
Sponsor:
Collaborator:
Astex Pharmaceuticals
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00506922
First received: July 20, 2007
Last updated: August 1, 2012
Last verified: August 2012
  Purpose

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:

  1. To determine safety of escalating doses of pentostatin in combination with tacrolimus and methotrexate.
  2. To reduce the incidence of acute GVHD following transplants with unrelated donor to 40%.
  3. To document blood levels of tacrolimus when combined with pentostatin.

Condition Intervention Phase
Leukemia
Lymphoma
Drug: Pentostatin
Drug: Tacrolimus
Drug: Methotrexate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Patients Without GVHD at 100 Days [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 150
Study Start Date: September 2000
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: No Pentostatin
Group 1: No Pentostatin
Drug: Pentostatin

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

Other Names:
  • Nipent
  • Deoxycoformycin
  • DCF
Drug: Tacrolimus
Given intravenously from day -2, and will be switched to oral dosing when tolerated.
Other Name: Prograf
Drug: Methotrexate
Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Experimental: Pentostatin 0.5
Group 2: Pentostatin 0.5 mg/m^2
Drug: Pentostatin

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

Other Names:
  • Nipent
  • Deoxycoformycin
  • DCF
Drug: Tacrolimus
Given intravenously from day -2, and will be switched to oral dosing when tolerated.
Other Name: Prograf
Drug: Methotrexate
Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Experimental: Pentostatin 1
Group 3: Pentostatin 1 mg/m^2
Drug: Pentostatin

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

Other Names:
  • Nipent
  • Deoxycoformycin
  • DCF
Drug: Tacrolimus
Given intravenously from day -2, and will be switched to oral dosing when tolerated.
Other Name: Prograf
Drug: Methotrexate
Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Experimental: Pentostatin 1.5
Group 4: Pentostatin 1.5 mg/m^2
Drug: Pentostatin

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

Other Names:
  • Nipent
  • Deoxycoformycin
  • DCF
Drug: Tacrolimus
Given intravenously from day -2, and will be switched to oral dosing when tolerated.
Other Name: Prograf
Drug: Methotrexate
Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Experimental: Pentostatin 2
Group 5: Pentostatin 2 mg/m^2
Drug: Pentostatin

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

Other Names:
  • Nipent
  • Deoxycoformycin
  • DCF
Drug: Tacrolimus
Given intravenously from day -2, and will be switched to oral dosing when tolerated.
Other Name: Prograf
Drug: Methotrexate
Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients receiving allogeneic hematopoietic transplants from an unrelated donor or one antigen mismatched related donors.
  2. 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.
  3. Patients must have bilirubin < 1.5 mg/dL, DLCO > 50% predicted, LVEF > 45% and performance status 0 or 1.
  4. Candidates must have a creatinine level < 1.5 mg/dL or a calculated creatinine clearance > 60 ml/min.

Exclusion Criteria:

  1. HIV seropositivity
  2. Uncontrolled infection
  3. Pregnancy
  4. 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.
  5. Diagnosis of myelofibrosis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00506922

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Astex Pharmaceuticals
Investigators
Principal Investigator: Marcos de Lima, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided by M.D. Anderson Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00506922     History of Changes
Other Study ID Numbers: ID00-132
Study First Received: July 20, 2007
Results First Received: March 1, 2011
Last Updated: August 1, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Graft-Versus-Host Disease
GVHD Prevention
Hodgkin's Disease
Leukemia
Lymphoma
Methotrexate
Tacrolimus
Pentostatin

Additional relevant MeSH terms:
Leukemia
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Methotrexate
Pentostatin
Tacrolimus
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Adenosine Deaminase Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014