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

Sponsors and Collaborators:	M.D. Anderson Cancer Center SuperGen
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00506922

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:

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.

Condition	Intervention	Phase
Leukemia Lymphoma	Drug: Pentostatin Drug: Tacrolimus Drug: Methotrexate	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma

Drug Information available for: Methotrexate Pentostatin Tacrolimus anhydrous Tacrolimus

U.S. FDA Resources

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

Primary Outcome Measures:

To learn if giving pentostatin with tacrolimus and methotrexate can improve the prevention of Graft-Versus-Host Disease (GVHD) in patients that have received cells from a matched unrelated donor or a mismatched related donor. [ Time Frame: 9 Years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To learn the highest safe dose of pentostatin that can be given with the other drugs. [ Time Frame: 9 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	150
Study Start Date:	September 2000
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1: Experimental No Pentostatin.	Drug: Tacrolimus Given intravenously from day -2, and will be switched to oral dosing when tolerated. Drug: Methotrexate Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Group 2: Experimental 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 Drug: Tacrolimus Given intravenously from day -2, and will be switched to oral dosing when tolerated. Drug: Methotrexate Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Group 3: Experimental 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 Drug: Tacrolimus Given intravenously from day -2, and will be switched to oral dosing when tolerated. Drug: Methotrexate Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Group 4: Experimental 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 Drug: Tacrolimus Given intravenously from day -2, and will be switched to oral dosing when tolerated. Drug: Methotrexate Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Group 5: Experimental 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 Drug: Tacrolimus Given intravenously from day -2, and will be switched to oral dosing when tolerated. 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:

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.

Contacts and Locations

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

SuperGen

Investigators

Principal Investigator:

Marcos de Lima, MD

U.T.M.D. Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	UT MD Anderson Cancer Center ( Marcos de Lima, MD/Associate Professor )
Study ID Numbers:	ID00-132
Study First Received:	July 20, 2007
Last Updated:	February 16, 2009
ClinicalTrials.gov Identifier:	NCT00506922 History of Changes
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

Study placed in the following topic categories:

Antimetabolites
Pentostatin
Immunoproliferative Disorders
Immunologic Factors
Hodgkin Lymphoma, Adult
Folate
Hodgkin's Disease
Tacrolimus
Folinic Acid
Folic Acid Antagonists
Immunosuppressive Agents
Vitamin B9

Homologous Wasting Disease
Folic Acid
Graft Versus Host Disease
Leukemia
Lymphatic Diseases
Graft vs Host Disease
Methotrexate
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma
Hodgkin Disease

Additional relevant MeSH terms:

Antimetabolites
Pentostatin
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Tacrolimus
Reproductive Control Agents
Leukemia
Therapeutic Uses
Abortifacient Agents
Methotrexate
Lymphoma

Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Enzyme Inhibitors
Abortifacient Agents, Nonsteroidal
Folic Acid Antagonists
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Antirheumatic Agents
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on September 03, 2009