Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies

NCT01188798 | Completed Phase 3 Results DMC

• 1 other identifier: MUDSIB
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine if participants who receive the GVHD prophylaxis medication pentostatin will have less severe hepatic toxicities than those receiving MTX. The study is estimated to have sufficient statistical power to ascertain at least a 20% improvement in day 42 NCI CTC grade 2 or above hepatic toxicity-free survival in pentostatin recipients.

Conditions

Acute Lymphoblastic Leukemia; Acute Myelocytic Leukemia; Chronic Myelocytic Leukemia; Hodgkin's Disease; Myelodysplastic Syndrome

Keywords

Allogeneic Bone Marrow Transplantation; Graft versus host disease; Tacrolimus; Sirolimus; Methotrexate; Pentostatin

Outcome Measures

Primary Outcomes (1)

• Determining Whether the Hepatic Adverse Event-free (NCI Grades II-IV) Survival at Day 42 After an HLA-matched Transplant for Hematologic Malignancy Can be Improved by Using a GVHD Prophylaxis Regimen That Includes Pentostatin Rather Than MTX.

  The hypothesis was that individuals receiving the drug pentostatin as GVHD prophylaxis would experience less severe hepatic toxicity than those receiving methotrexate as GVHD prophylaxis. The study is estimated to have sufficient statistical power to ascertain at least a 20% improvement in day 42 grade 2 or above hepatic toxicity-free survival in pentostatin recipients

  42 days post-transplant

Secondary Outcomes (1)

• Assess Overall Survival, Relapse, Engraftment, and Regimen-related Morbidity and Estimating Cumulative Incidence of Pulmonary Adverse Events and Mucositis.

  42 days post- transplant

Study Arms (2)

Transplant recipients receiving Methotrexate

EXPERIMENTAL

Participants will be biologically stratified according to disease, donor, and KIR match. In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin)

Drug: Methotrexate

Transplant recipients receiving Pentostatin

EXPERIMENTAL

Participants will be biologically stratified according to disease, donor, and KIR match.between donor and host.In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin)

Drug: Pentostatin

Interventions

Methotrexate DRUG

Participants will be randomized to receive either methotrexate (MTX) or pentostatin for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.

Transplant recipients receiving Methotrexate

Pentostatin DRUG

Participants will be randomized to receive either methotrexate (MTX) or pentostatin for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.

Transplant recipients receiving Pentostatin

Eligibility Criteria

• Age: 18 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \*Age less than or equal to 21 years old
• High risk malignancy as follows:
• High-risk ALL in CR1. Examples include, but not limited to: Induction failure or \> 1% leukemic lymphoblasts in the bone marrow on remission date;\> 0.1% leukemic lymphoblasts in the bone marrow in week 7 of continuation treatment (i.e. before reinduction I); re-emergence of leukemic lymphoblasts by MRD (at any level) in patients previously MRD negative; persistently detectable MRD at lower levels;early T-cell precursor (ETP) ALL.
• High-risk ALL beyond CR1, or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state. "Refractory disease" includes induction failure.
• High-risk de novo AML in CR1.Examples include but are not limited to:evidence of a high-risk genetic abnormality or high-risk MRD features.
• AML beyond CR1, or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state. "Refractory disease" includes induction failure.
• Therapy-related AML.
• MDS, primary or secondary, at any stage.
• NK cell lymphoblastic leukemia in any CR
• Biphenotypic bilineage, or undifferentiated leukemia.
• CML in any phase
• Hodgkin lymphoma beyond CR1 or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state.
• Non-Hodgkin lymphoma beyond CR1 or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state.
• Juvenile Myelomonocytic Leukemia (JMML).
• All patients with prior evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study.

You may not qualify if:

• Pregnant and lactating females are excluded from participation as the short and long-term effects of the protocol interventions and infusion on a fetus or a nursing child through breast milk are not entirely known at this time.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St . Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hodgkin Disease; Myelodysplastic Syndromes; Graft vs Host Disease

Interventions

Methotrexate; Pentostatin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

This study was terminated prematurely. The Data Safety and Monitoring Board (DSMB) requested major scientific study changes. This was deemed infeasible by institutional leadership and study was terminated. Therefore, no final results exist to report.

Results Point of Contact

• Title: Asha Pillai, MD
• Organization: St. Jude Children's Research Hospital

info@stjude.org

1-866-278-5833

Study Officials

• Asha Pillai, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2010
• First Posted: August 25, 2010
• Study Start: September 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: March 21, 2013
• Results First Posted: March 14, 2013

Record last verified: 2012-02

Locations

US (1)