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

Registration Number
NCT04872595
Lead Sponsor
Memorial Sloan Kettering Cancer Center
Brief Summary

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...

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
59
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.

Read More
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

Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
P-rATG with total body irradiation, thiotepa, cyclophosphamidePersonalized rATG (P-rATG)P-rATG days (always starting on Day -12 to -10) * Hyper fractionated total body irradiation (1375 - 1500cGy\*) Day -9 to -6 * Thiotepa (5mg/kg/day x 2 day) Day -5 to -4 * Cyclophosphamide (60mg/kg/day x 2 days) Day -3 to -2 * GCSF Day +7 \*TBI dose in 125cGy fractions (with lung shielding) and total dose to be determined by treating physician/radiation oncology and is based off age, stage of disease, and anesthesia requirements.
P-rATG with total body irradiation, thiotepa, cyclophosphamideGCSFP-rATG days (always starting on Day -12 to -10) * Hyper fractionated total body irradiation (1375 - 1500cGy\*) Day -9 to -6 * Thiotepa (5mg/kg/day x 2 day) Day -5 to -4 * Cyclophosphamide (60mg/kg/day x 2 days) Day -3 to -2 * GCSF Day +7 \*TBI dose in 125cGy fractions (with lung shielding) and total dose to be determined by treating physician/radiation oncology and is based off age, stage of disease, and anesthesia requirements.
P-rATG with total body irradiation, thiotepa, cyclophosphamideHyper fractionated total body irradiationP-rATG days (always starting on Day -12 to -10) * Hyper fractionated total body irradiation (1375 - 1500cGy\*) Day -9 to -6 * Thiotepa (5mg/kg/day x 2 day) Day -5 to -4 * Cyclophosphamide (60mg/kg/day x 2 days) Day -3 to -2 * GCSF Day +7 \*TBI dose in 125cGy fractions (with lung shielding) and total dose to be determined by treating physician/radiation oncology and is based off age, stage of disease, and anesthesia requirements.
P-rATG with total body irradiation, thiotepa, cyclophosphamideThiotepaP-rATG days (always starting on Day -12 to -10) * Hyper fractionated total body irradiation (1375 - 1500cGy\*) Day -9 to -6 * Thiotepa (5mg/kg/day x 2 day) Day -5 to -4 * Cyclophosphamide (60mg/kg/day x 2 days) Day -3 to -2 * GCSF Day +7 \*TBI dose in 125cGy fractions (with lung shielding) and total dose to be determined by treating physician/radiation oncology and is based off age, stage of disease, and anesthesia requirements.
P-rATG with total body irradiation, thiotepa, cyclophosphamideCyclophosphamideP-rATG days (always starting on Day -12 to -10) * Hyper fractionated total body irradiation (1375 - 1500cGy\*) Day -9 to -6 * Thiotepa (5mg/kg/day x 2 day) Day -5 to -4 * Cyclophosphamide (60mg/kg/day x 2 days) Day -3 to -2 * GCSF Day +7 \*TBI dose in 125cGy fractions (with lung shielding) and total dose to be determined by treating physician/radiation oncology and is based off age, stage of disease, and anesthesia requirements.
P-rATG with busulfan, melphalan and fludarabinePersonalized rATG (P-rATG)P-rATG days (Appendix A - always starting on Day -12 to -10) * Busulfan -Day -9 to -7 * Initial dose per table in Appendix B; doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg\*h/L Melphalan (70mg/m2/day x 2 days) Day -6 to -5 * Fludarabine (25mg/m2/day x 5 days) Day -6 to -2 * GCSF Day +7
P-rATG with busulfan, melphalan and fludarabineGCSFP-rATG days (Appendix A - always starting on Day -12 to -10) * Busulfan -Day -9 to -7 * Initial dose per table in Appendix B; doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg\*h/L Melphalan (70mg/m2/day x 2 days) Day -6 to -5 * Fludarabine (25mg/m2/day x 5 days) Day -6 to -2 * GCSF Day +7
P-rATG with busulfan, melphalan and fludarabineBusulfanP-rATG days (Appendix A - always starting on Day -12 to -10) * Busulfan -Day -9 to -7 * Initial dose per table in Appendix B; doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg\*h/L Melphalan (70mg/m2/day x 2 days) Day -6 to -5 * Fludarabine (25mg/m2/day x 5 days) Day -6 to -2 * GCSF Day +7
P-rATG with busulfan, melphalan and fludarabineMelphalanP-rATG days (Appendix A - always starting on Day -12 to -10) * Busulfan -Day -9 to -7 * Initial dose per table in Appendix B; doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg\*h/L Melphalan (70mg/m2/day x 2 days) Day -6 to -5 * Fludarabine (25mg/m2/day x 5 days) Day -6 to -2 * GCSF Day +7
P-rATG with busulfan, melphalan and fludarabineFludarabineP-rATG days (Appendix A - always starting on Day -12 to -10) * Busulfan -Day -9 to -7 * Initial dose per table in Appendix B; doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg\*h/L Melphalan (70mg/m2/day x 2 days) Day -6 to -5 * Fludarabine (25mg/m2/day x 5 days) Day -6 to -2 * GCSF Day +7
Primary Outcome Measures
NameTimeMethod
proportion of patients who achieve CD4+IRwithin 100 days of HCT

is defined at CD4+ \> 50u/L at two consecutive measures within 100 days post allo-HCT.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)2 years

The duration of time between HCT and death due to any cause.

Trial Locations

Locations (1)

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

© Copyright 2024. All Rights Reserved by MedPath
HomeTerms & ConditionsPrivacy Policy