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

NCT04872595 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 21-193
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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)

Keywords

personalized rabbit ATG (P-rATG); ex-vivo CD34+ T cell depleted; total body irradiation; thiotepa; cyclophosphamide; busulfan; melphalan; fludarabine; 21-193

Outcome Measures

Primary Outcomes (1)

• proportion of patients who achieve CD4+IR

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

  within 100 days of HCT

Secondary Outcomes (1)

• Overall Survival (OS)

  2 years

Study Arms (2)

P-rATG with total body irradiation, thiotepa, cyclophosphamide

EXPERIMENTAL

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.

Other: Personalized rATG (P-rATG); Radiation: Hyper fractionated total body irradiation; Drug: Thiotepa; Drug: Cyclophosphamide; Drug: GCSF

P-rATG with busulfan, melphalan and fludarabine

EXPERIMENTAL

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

Other: Personalized rATG (P-rATG); Drug: GCSF; Drug: Busulfan; Drug: Melphalan; Drug: Fludarabine

Interventions

Busulfan DRUG

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

P-rATG with busulfan, melphalan and fludarabine

Melphalan DRUG

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

P-rATG with busulfan, melphalan and fludarabine

Fludarabine DRUG

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

P-rATG with busulfan, melphalan and fludarabine

Personalized rATG (P-rATG) OTHER

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

P-rATG with busulfan, melphalan and fludarabine; P-rATG with total body irradiation, thiotepa, cyclophosphamide

Hyper fractionated total body irradiation 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.

P-rATG with total body irradiation, thiotepa, cyclophosphamide

Thiotepa DRUG

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

P-rATG with total body irradiation, thiotepa, cyclophosphamide

Cyclophosphamide DRUG

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

P-rATG with total body irradiation, thiotepa, cyclophosphamide

GCSF DRUG

Day +7

P-rATG with busulfan, melphalan and fludarabine; P-rATG with total body irradiation, thiotepa, cyclophosphamide

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Scordo M, Perales MA, Mauguen A, Lin A, Kunvarjee B, Paes Pena M, Mcavoy D, Nguyen LK, Hogan M, Chapman N, Bieler J, Cho C, Gyurkocza B, Harris AC, Spitzer B, O'Reilly RJ, Jakubowski AA, Lin RJ, Papadopoulos EB, Politikos I, Ponce DM, Shaffer BC, Shah GL, Tamari R, Giralt SA, Boelens JJ, Curran KJ. Model-based antithymocyte globulin dosing in ex vivo CD34+ selected allogeneic haematopoietic cell transplantation: a single-centre, single-arm, phase 2 study. Lancet Haematol. 2025 Dec;12(12):e956-e965. doi: 10.1016/S2352-3026(25)00293-5.

  PMID: 41338864 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes

Interventions

Thiotepa; Cyclophosphamide; Busulfan; Melphalan; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Kevin Curran, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This phase 2 study is to assess the effects of personalized rabbit ATG (P-rATG) dosing on CD4+ immune reconstitution (CD4+IR) based on a pharmacokinetic/pharmacodynamic (PK/PD) model in patients with hematologic malignancies undergoing peripheral blood mobilized, ex-vivo CD34+ T cell depleted, allogeneic, hematopoietic cell transplantation (CD34+/TCD allo-HCT)1.

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: May 4, 2021
• Study Start: April 30, 2021
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)