IRB Study Number 23-153
Status Recruiting
Institute Taussig Cancer Institute
Description
1.1 Primary Objectives
1.1.1 To compare the 1-year cumulative incidence of severe GVHD (from day of HCT) defined as Grade III-IV acute GVHD (aGVHD) and/or chronic GVHD (cGVHD) that requires systemic immunosuppression and to compare the disease free survival (DFS) (from time of randomization) in children and young adults (AYA) with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and Myelodysplastic Syndrome (MDS) who are randomly assigned to haploHCT or to an 8/8 adult MUD HCT.
1.2 Secondary Objectives
1.2.1 To compare overall survival (OS) between children and AYA with AML/ALL/MDS randomly assigned to haploHCT and MUD HCT.
1.2.2 To compare differences in health-related quality of life (HRQOL) between haploHCT and MUD HCT from baseline (pre-transplant), at 6 months, 1 year and 2 years post-transplant.
Inclusion Criteria
4.2.1 Disease criteria as per Section 4.2.4-4.2.5.
4.2.2 Performance Level
Karnofsky Index or Lansky Play-Performance Scale ≥ 60 on pre-transplant evaluation. Karnofsky scores must be used for patients ≥ 16 years of age and Lansky scores for patients < 16 years of age.
4.2.3 Organ Function Requirements
4.2.3.1 Adequate renal function defined as:
-A serum creatinine based on age/gender as follows: (see protocol)
OR - a 24 hour urine Creatinine clearance ≥ 60 mL/min/1.73 m2
OR - a GFR ≥ 60 mL/min/1.73 m2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
4.2.3.2 Adequate liver function defined as:
- SGOT (AST) or SGPT (ALT) < 5 x upper limit of normal (ULN) for age. Total bilirubin < 2.5 mg/dL, unless attributable to Gilbert’s Syndrome.
4.2.3.3 Adequate cardiac function defined as:
Shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA) or
Ejection fraction of ≥ 50% by echocardiogram or radionuclide scan (MUGA), choice of test according to local standard of care.
4.2.3.4 Adequate pulmonary function defined as:
FEV1, FVC, and corrected DLCO must all be ≥ 50% of predicted by pulmonary function tests (PFTs).
For children who are unable to perform for PFTs (e.g., due to age or developmental delay), the criteria are: no evidence of dyspnea at rest, O2 Sat > 92% on room air by pulse oximetry, not on supplemental O2 at rest, and not on supplemental O2 at rest.
4.2.4 ALL Criteria
4.2.4.1 ALL high-risk in CR1* for whom transplant is indicated. Examples include: induction failure, treatment failure as per minimal residual disease by flow cytometry >0.01% after consolidation and not eligible for AALL1721 or AALL1721 not available/unwilling to enroll, hypodiploidy (<44 chromosomes) with MRD+ >0.01% after induction, persistent or recurrent cytogenetic or molecular evidence of disease during therapy requiring additional therapy after induction to achieve remission (e.g. persistent molecular BCR-ABL positivity), T cell ALL with persistent MRD>0.01% after consolidation.
4.2.4.2 ALL in CR2* for whom transplant is indicated. Examples include: B-cell: early (<36 months from initiation of therapy) BM relapse, late BM relapse (≥ 36 months) with MRD >0.1% by flow cytometry after first re-induction therapy; T or B-cell: early (<18 months) IEM, late (≥ 18 months) IEM, end-Block 1 MRD ≥ 0.1%; T-cell or Ph+: BM relapse at any time.
4.2.4.3 ALL in > CR3*
4.2.4.4 Patients treated with CART cells for whom transplant is indicated. Examples include: transplant for consolidation of CART, loss of CART persistence and/or B cell aplasia <6 months from infusion or have other evidence (e.g., MRD+) that transplant is indicated to prevent relapse.
4.2.5 AML/MDS Criteria
4.2.5.1 AML in CR1* for whom transplant is indicated. Examples include those deemed high risk for relapse as described in AAML1831:
-FLT3/ITD+ with allelic ratio > 0.1 without bZIP CEBPA, NPM1
-FLT3/ITD+ with allelic ratio > 0.1 with concurrent bZIP CEBPA or NPM1 and with evidence of residual AML (MRD ≥ 0.05%) at end of Induction
-Presence of RAM phenotype or unfavorable prognostic markers (other than FLT3/ITD) per cytogenetics, FISH, NGS results, regardless of favorable genetic markers, MRD status or FLT3/ITD mutation status
-AML without favorable or unfavorable cytogenetic or molecular features but with evidence of residual AML (MRD ≥ 0.05%) at end of Induction
-Presence of a non-ITD FLT3 activating mutation and positive MRD (≥ 0.05%) at end of Induction 1 regardless of presence of favorable genetic markers.
4.2.5.2 AML in > CR2
4.2.5.3 MDS with <5% blasts by morphology and flow cytometry (if available) on the pre-transplant bone marrow evaluation
*Complete remission (CR) is defined as <5% blasts by morphology and flow cytometry (if available) on the pre-transplant bone marrow evaluation with minimum sustained ANC of 300 cells/microliter for 1 week or ANC >500 cells/microliter. We will be collecting data from all approaches to MRD evaluation performed including NGS and PCR.
Exclusion Criteria
4.2.6 Patients with uncontrolled fungal, bacterial, viral, or parasitic infections are excluded. Patients with history of fungal disease during chemotherapy may proceed if they have a significant response to antifungal therapy with no or minimal evidence of disease remaining by CT evaluation.
4.2.7 Patients with active CNS leukemia or any other active site of extramedullary disease at the time of initiation of the conditioning regimen are not permitted. Note: Those with prior history of CNS or extramedullary disease, but with no active disease at the time of pre-transplant workup, are eligible.
4.2.8 Pregnancy and Breastfeeding
Pregnant or breastfeeding females are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants
