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


Phase 3
18 Months
21 Years
Not Enrolling
Both
Acute Lymphoblastic Leukemia, Acute Myelocytic Leukemia, Chronic Myelocytic Leukemia, Hodgkin's Disease, Myelodysplastic Syndrome

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Trial Information

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


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.


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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Description:

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

Outcome Time Frame:

42 days post-transplant

Safety Issue:

Yes

Principal Investigator

Asha Pillai, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

St. Jude Children's Research Hospital

Authority:

United States: Institutional Review Board

Study ID:

MUDSIB

NCT ID:

NCT01188798

Start Date:

September 2010

Completion Date:

February 2012

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • Acute Myelocytic Leukemia
  • Chronic Myelocytic Leukemia
  • Hodgkin's Disease
  • Myelodysplastic Syndrome
  • Allogeneic Bone Marrow Transplantation
  • Graft versus host disease
  • Tacrolimus
  • Sirolimus
  • Methotrexate
  • Pentostatin
  • Graft vs Host Disease
  • Hodgkin Disease
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hematologic Neoplasms

Name

Location

St . Jude Children's Research HospitalMemphis, Tennessee  38105