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

NCT ID: NCT04872595

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-30
• Study Completion Date: 2026-04-30

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 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).

Conditions

Acute Myeloid Leukemia (AML); Acute Lymphoid Leukemia (ALL); Myelodysplastic Syndromes (MDS)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

P-rATG with total body irradiation, thiotepa, cyclophosphamide

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.

Group Type: EXPERIMENTAL

Personalized rATG (P-rATG)

Intervention Type: OTHER

P-rATG days (always starting on Day -12 to -10)

Hyper fractionated total body irradiation

Intervention Type: RADIATION

(1375 - 1500cGy*) Day -9 to -6

*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.

Thiotepa

Intervention Type: DRUG

(5mg/kg/day x 2 day) Day -5 to -4

Cyclophosphamide

Intervention Type: DRUG

(60mg/kg/day x 2 days) Day -3 to -2

GCSF

Intervention Type: DRUG

Day +7

P-rATG with busulfan, melphalan and fludarabine

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

Group Type: EXPERIMENTAL

Personalized rATG (P-rATG)

Intervention Type: OTHER

P-rATG days (always starting on Day -12 to -10)

GCSF

Intervention Type: DRUG

Day +7

Busulfan

Intervention Type: DRUG

Day -9 to -7 doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg\*h/L

Melphalan

Intervention Type: DRUG

(70mg/m2/day x 2 days) Day -6 to -5

Fludarabine

Intervention Type: DRUG

(25mg/m2/day x 5 days) Day -6 to -2

Interventions

Personalized rATG (P-rATG)

P-rATG days (always starting on Day -12 to -10)

Intervention Type: OTHER

Hyper fractionated total body irradiation

(1375 - 1500cGy*) Day -9 to -6

*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.

Intervention Type: RADIATION

Thiotepa

(5mg/kg/day x 2 day) Day -5 to -4

Intervention Type: DRUG

Cyclophosphamide

(60mg/kg/day x 2 days) Day -3 to -2

Intervention Type: DRUG

GCSF

Day +7

Intervention Type: DRUG

Busulfan

Day -9 to -7 doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg\*h/L

Intervention Type: DRUG

Melphalan

(70mg/m2/day x 2 days) Day -6 to -5

Intervention Type: DRUG

Fludarabine

(25mg/m2/day x 5 days) Day -6 to -2

Intervention Type: DRUG

Eligibility Criteria

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.

• 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

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.

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kevin Curran, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Related Links

http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

21-193

Identifier Type: -

Identifier Source: org_study_id