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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01188798
First received: August 24, 2010
Last updated: March 14, 2013
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Acute Myelocytic Leukemia
Chronic Myelocytic Leukemia
Hodgkin's Disease
Myelodysplastic Syndrome
Drug: Methotrexate
Drug: Pentostatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • 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. [ Time Frame: 42 days post-transplant ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Assess Overall Survival, Relapse, Engraftment, and Regimen-related Morbidity and Estimating Cumulative Incidence of Pulmonary Adverse Events and Mucositis. [ Time Frame: 42 days post- transplant ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetic-pharmacodynamic relationships of pentostatin in this patient population and to assess the relationship between pre-transplant minimal residual disease (MRD) and transplant outcomes.


Enrollment: 6
Study Start Date: September 2010
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transplant recipients receiving Methotrexate
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
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.
Experimental: Transplant recipients receiving Pentostatin
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
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.

Detailed Description:

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. All participants will receive a standard backbone GVHD prophylaxis regimen (tacrolimus and sirolimus) and conditioning (cyclophosphamide/TBI). A risk-adapted approach will be used during conditioning to further minimize the risk of leukemia relapse based on two factors:

  1. Lymphoid versus myeloid primary disease.
  2. KIR compatibility between donor and host.
  Eligibility

Ages Eligible for Study:   18 Months to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

*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.
  • Has a suitable HLA matched sibling or unrelated volunteer donor available for stem cell donation.A "matched" donor is defined as allele matching at 7/8 to 8/8 HLA loci at A, B, C and DRB1.For the purpose of this study, the term "matched sibling" also refers to an HLA matched family member.
  • Does not have any other active malignancy other than the one for which this transplant is indicated.
  • Left ventricular ejection fraction > 40%,or shortening fraction > 26%.
  • Forced vital capacity (FVC) greater than or equal to 50% of predicted value (corrected for hemoglobin), or if patient is unable to perform pulmonary function testing, pulse oximetry greater than or equal to 92% on room air.
  • Creatinine clearance greater than or equal to 70 ml/min/1.73m2
  • Karnofsky or Lansky (age-dependent) performance score of greater than or equal to 70.
  • Bilirubin less than or equal to 2.5 mg/dL.
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than or equal to 5 times upper limit of normal
  • Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment.
  • Not lactating.
  • Has not had a prior allogeneic HSCT.

Exclusion Criteria:

  • 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.
  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: NCT01188798

Locations
United States, Tennessee
St . Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Asha Pillai, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01188798     History of Changes
Other Study ID Numbers: MUDSIB
Study First Received: August 24, 2010
Results First Received: February 12, 2013
Last Updated: March 14, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Allogeneic Bone Marrow Transplantation
Graft versus host disease
Tacrolimus
Sirolimus
Methotrexate
Pentostatin

Additional relevant MeSH terms:
Graft vs Host Disease
Hodgkin Disease
Leukemia
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoproliferative Disorders
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions
Methotrexate
Pentostatin
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Adenosine Deaminase Inhibitors
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 29, 2014