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

Phase 1

Completed

• Conditions: Lymphoma; Leukemia
• Interventions: Drug: Pentostatin; Drug: Tacrolimus; Drug: Methotrexate

• Registration Number: NCT00506922
• Lead Sponsor: M.D. Anderson Cancer Center

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:

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.

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 Timeline

• Study Start: 2000-09
• Study First Submitted: 2007-07-20
• Study First Submitted QC: 2007-07-20
• Study First Posted: 2007-07-25
• Primary Completion: 2009-11
• Study Completion: 2009-11
• Results First Submitted: 2011-03-01
• Results First Submitted QC: 2011-03-01
• Results First Posted: 2011-03-28
• Status Verified: 2012-08
• Last Update Submitted: 2015-04-06
• Last Update Posted: 2015-04-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pentostatin 1	Methotrexate	Group 3: Pentostatin 1 mg/m\^2
Pentostatin 0.5	Tacrolimus	Group 2: Pentostatin 0.5 mg/m\^2
Pentostatin 1.5	Tacrolimus	Group 4: Pentostatin 1.5 mg/m\^2
Pentostatin 0.5	Methotrexate	Group 2: Pentostatin 0.5 mg/m\^2
No Pentostatin	Methotrexate	Group 1: No Pentostatin
No Pentostatin	Tacrolimus	Group 1: No Pentostatin
No Pentostatin	Pentostatin	Group 1: No Pentostatin
Pentostatin 0.5	Pentostatin	Group 2: Pentostatin 0.5 mg/m\^2
Pentostatin 1.5	Methotrexate	Group 4: Pentostatin 1.5 mg/m\^2
Pentostatin 1	Pentostatin	Group 3: Pentostatin 1 mg/m\^2
Pentostatin 1	Tacrolimus	Group 3: Pentostatin 1 mg/m\^2
Pentostatin 1.5	Pentostatin	Group 4: Pentostatin 1.5 mg/m\^2
Pentostatin 2	Pentostatin	Group 5: Pentostatin 2 mg/m\^2
Pentostatin 2	Tacrolimus	Group 5: Pentostatin 2 mg/m\^2
Pentostatin 2	Methotrexate	Group 5: Pentostatin 2 mg/m\^2

Primary Outcome Measures

Name	Time	Method
Number of Patients Without GVHD at 100 Days	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.

Trial Locations

Locations (1)

U.T.M.D. Anderson Cancer Center; 🇺🇸 Houston, Texas, United States