Clinical trial NCT04872595: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2021-05-04
Enrollment: 59
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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).


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.

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

Primary outcomes:
measure: proportion of patients who achieve CD4+IR
timeFrame: within 100 days of HCT
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Kevin Curran, MD
role: PRINCIPAL_INVESTIGATOR
References: