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

April 17, 2024 updated by: Memorial Sloan Kettering Cancer Center

Phase 2 Study of Personalized r-ATG Dosing to Improve Survival Through Enhanced Immune Reconstitution in Pediatric and Adult Patients Undergoing Ex-vivo CD34-Selected Allogeneic-HCT (PRAISE-IR)

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

59

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Michael Scordo, MD
  • Phone Number: 646-608-3771

Study Contact Backup

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: Personalized rATG (P-rATG)
P-rATG days (always starting on Day -12 to -10)
Radiation: 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.

Drug: Thiotepa
(5mg/kg/day x 2 day) Day -5 to -4
Drug: Cyclophosphamide
(60mg/kg/day x 2 days) Day -3 to -2
Drug: GCSF
Day +7
Experimental: 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
Other: Personalized rATG (P-rATG)
P-rATG days (always starting on Day -12 to -10)
Drug: GCSF
Day +7
Drug: Busulfan
Day -9 to -7 doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg*h/L
Drug: Melphalan
(70mg/m2/day x 2 days) Day -6 to -5
Drug: Fludarabine
(25mg/m2/day x 5 days) Day -6 to -2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
proportion of patients who achieve CD4+IR
Time Frame: within 100 days of HCT
is defined at CD4+ > 50u/L at two consecutive measures within 100 days post allo-HCT.
within 100 days of HCT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 2 years
The duration of time between HCT and death due to any cause.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Investigators

  • Principal Investigator: Kevin Curran, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 30, 2021

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

April 30, 2021

First Submitted That Met QC Criteria

April 30, 2021

First Posted (Actual)

May 4, 2021

Study Record Updates

Last Update Posted (Actual)

April 18, 2024

Last Update Submitted That Met QC Criteria

April 17, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21-193

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made following one year after publication and for up to 36 months later. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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