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
- Conditions
- Acute Myeloid Leukemia (AML)Acute Lymphoid Leukemia (ALL)Myelodysplastic Syndromes (MDS)
- Interventions
- Other: Personalized rATG (P-rATG)Radiation: Hyper fractionated total body irradiationDrug: GCSF
- Registration Number
- NCT04872595
- Lead Sponsor
- Memorial Sloan Kettering Cancer Center
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 59
-
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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description P-rATG with total body irradiation, thiotepa, cyclophosphamide Personalized rATG (P-rATG) 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. P-rATG with total body irradiation, thiotepa, cyclophosphamide GCSF 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. P-rATG with total body irradiation, thiotepa, cyclophosphamide Hyper fractionated total body irradiation 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. P-rATG with total body irradiation, thiotepa, cyclophosphamide Thiotepa 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. P-rATG with total body irradiation, thiotepa, cyclophosphamide 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. P-rATG with busulfan, melphalan and fludarabine Personalized rATG (P-rATG) 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 P-rATG with busulfan, melphalan and fludarabine GCSF 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 P-rATG with busulfan, melphalan and fludarabine Busulfan 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 P-rATG with busulfan, melphalan and fludarabine Melphalan 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 P-rATG with busulfan, melphalan and fludarabine 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
- Primary Outcome Measures
Name Time Method proportion of patients who achieve CD4+IR within 100 days of HCT is defined at CD4+ \> 50u/L at two consecutive measures within 100 days post allo-HCT.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) 2 years The duration of time between HCT and death due to any cause.
Trial Locations
- Locations (1)
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States