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

• Status: Recruiting
• Trial end date: 2024-04-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Memorial Sloan Kettering Cancer Center
• Treatments: Busulfan; Cyclophosphamide; Fludarabine; Melphalan; Thiotepa

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.

Donor Inclusion Criteria:

• Related Donors:

°8/8 or 7/8 HLA matched at A, B, C, and DRB1 loci, as tested by DNA analysis.

• Unrelated Donors:

°8/8 or 7/8 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