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Trial record 24 of 34 for:    "Leukemia" | "Pentostatin"

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

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ClinicalTrials.gov Identifier: NCT01188798
Recruitment Status : Completed
First Posted : August 25, 2010
Results First Posted : March 14, 2013
Last Update Posted : March 21, 2013
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Tracking Information
First Submitted Date  ICMJE August 24, 2010
First Posted Date  ICMJE August 25, 2010
Results First Submitted Date  ICMJE February 12, 2013
Results First Posted Date  ICMJE March 14, 2013
Last Update Posted Date March 21, 2013
Study Start Date  ICMJE September 2010
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2013)
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 ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: August 24, 2010)
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 ]
Participants who receive the GVHD prophylaxis medication pentostatin will have less 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 grade 2 or above hepatic toxicity-free survival in pentostatin recipients
Change History Complete list of historical versions of study NCT01188798 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2013)
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 ]
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2010)
Assessing overall survival, relapse, engraftment, and regimen-related morbidity and estimating cumulative incidence of pulmonary adverse events and mucositis in study participants who receive pentostatin versus those who receive MTX. [ Time Frame: 42 days post- transplant ]
To characterize the pharmacokinetic-pharmacodynamic relationships of pentostatin in this patient population.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies
Official Title  ICMJE Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Lymphoblastic Leukemia
  • Acute Myelocytic Leukemia
  • Chronic Myelocytic Leukemia
  • Hodgkin's Disease
  • Myelodysplastic Syndrome
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • 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)
    Intervention: Drug: Methotrexate
  • 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)
    Intervention: Drug: Pentostatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 22, 2012)
6
Original Estimated Enrollment  ICMJE
 (submitted: August 24, 2010)
165
Actual Study Completion Date  ICMJE February 2012
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Months to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01188798
Other Study ID Numbers  ICMJE MUDSIB
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party St. Jude Children's Research Hospital
Study Sponsor  ICMJE St. Jude Children's Research Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Asha Pillai, MD St. Jude Children's Research Hospital
PRS Account St. Jude Children's Research Hospital
Verification Date February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP