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

April 6, 2015 updated by: M.D. Anderson Cancer Center

Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After Matched-Unrelated Donor Blood and Marrow Transplantation

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • U.T.M.D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients Without GVHD at 100 Days
Time Frame: 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.
100 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

Astex Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2000

Primary Completion (ACTUAL)

November 1, 2009

Study Completion (ACTUAL)

November 1, 2009

Study Registration Dates

First Submitted

July 20, 2007

First Submitted That Met QC Criteria

July 20, 2007

First Posted (ESTIMATE)

July 25, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

April 28, 2015

Last Update Submitted That Met QC Criteria

April 6, 2015

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ID00-132

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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