A Modified Dose of Rabbit Anti-thymocyte Globulin (rATG) in Children and Adults Receiving Treatment to Help Prepare Their Bodies for a Bone Marrow Transplant

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Overview

The purpose of this study is to see if conditioning regimens that include personalized rabbit ATG (P-rATG) help the immune system recover sooner and decrease the chances of transplant-related side effects. Participants in this study will be children and adults who have acute leukemia or myelodysplastic syndrome (MDS), and will receive a standard conditioning regimen to prepare the body for an allogeneic hematopoietic cell transplant (allo-HCT). The conditioning regimen will include r-ATG, one of two combinations of chemotherapy, and possibly total body irradiation (TBI).

SparkCures ID 1265
Trial Phase Phase 2
Enrollment 59 Patients
Treatments
Tags
  • Chemotherapy
  • Myeloablative Conditioning (MAC)
  • Pre-Allogeneic Stem Cell Transplant
  • Radiation Therapy
Trial Sponsors
  • Memorial Sloan Kettering Cancer Center
NCT Identifier

NCT04872595

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

Inclusion Criteria:

  • Patients receiving first peripheral blood mobilized ex-vivo CD34-selected T cell depleted allo-HCT for the following hematologic malignant conditions:
    • Acute myeloid leukemia (AML) with intermediate or high-risk features in CR1 or Relapse AML in ≥ CR2.
    • Must have MRD <5% (flow cytometry, molecular and/or cytogenetics accepted).
    • Acute leukemias of ambiguous lineage in ≥ CR1.
    • Must have MRD <5% (flow cytometry, molecular and/or cytogenetics accepted).
    • Acute lymphoid leukemia (ALL) in CR1 with clinical, flow cytometric, or molecular features indicating a high risk for relapse, or ALL in ≥ CR2.
    • Adult Patients - recommended but not required to be MRDnegative (by flow cytometry, molecular and/or cytogenetics).
    • Pediatric Patients - Must be MRD-negative by flow cytometry, molecular and/or cytogenetics.
    • Myelodysplastic syndromes (MDS) with least one of the following:
    • Revised International Prognostic Scoring System risk score of intermediate or higher at the time of transplant evaluation.
    • Life-threatening cytopenia.
    • Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.
    • Therapy related disease or disease evolving from other malignant processes.
  • Able to tolerate cytoreduction
  • Patients age:
    • Regimen A: 4 - 60 years
    • Regimen B - no age restriction
  • Adequate organ function is required, defined as follows:
    • Hepatic: Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia. Patients with hyperbilirubinemia related to paroxysmal nocturnal hemoglobinuria or other hemolytic disorders are eligible with PI approval.
    • Hepatic: AST, ALT, and alkaline phosphatase < 2.5 times the upper limit of normal unless thought to be disease-related.
    • Renal: serum creatinine <1.5x normal for age. If serum creatinine is outside the normal range, then CrCl > 50 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.72m2) >30% of predicted normal for age.
  • Normal GFR by Age
    • 1 week 40.6 + / - 14.8
    • 2 - 8 weeks 65.8 + / - 24.8
    • > 8 weeks 95.7 +/- 21.7
    • 2 - 12 years 133 +/- 27
    • 13 - 21 years (males) 140 +/- 30
    • 13 - 21 years (females) 126.0 + / - 22.0
  • Cardiac: LVEF ≥ 50% by MUGA or resting echocardiogram.
  • Pulmonary: Pulmonary function testing (FEV1 and corrected DLCO) ≥ 50% predicted (pediatric patients unable to complete PFTs will need oxygen saturation as recorded by pulse oximetry of ≥92% on room air).
  • Adequate performance status:
    • Age ≥ 16 years: ECOG ≤ 1 or Karnofsky 70%
    • Age < 16 years: Lansky 70%
  • Each patient must be willing to participate as a research subject and must sign an informed consent form or legal guardian with assent as appropriate.

Exclusion Criteria:

  • Patients with active extramedullary disease.
  • Patients with active central nervous system malignancy.
  • Uncontrolled infection at the time of allo-HCT.
  • Patients who have undergone previous allo-HCT.
  • Patient seropositivity for HIV I/II and/or HTLV I/II.
  • Females who are pregnant or breastfeeding.
  • Patients unwilling to use contraception during the study period.
  • Patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests.

Donor Inclusion Criteria:

  • Related or Unrelated Donors:
    • 8/8 HLA matched at A, B, C, and DRB1 loci, as tested by DNA analysis.
    • Able to provide informed consent for the donation process per institutional standards.
    • Meet standard criteria for donor collection (e.g. National Marrow Donor Program Guidelines or collecting center guidelines as approved by treating physician).
    • Provide GSCF mobilized peripheral blood stem cells

US Trial Locations

Please visit the ClinicalTrials.gov page for historical site information.

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