A Phase II Pilot Trial to Estimate Survival After a Non-total Body Irradiation (TBI) Based Conditioning Regimen in Patients Diagnosed With B-acute Lymphoblastic Leukemia (ALL) Who Are Pre-allogeneic Hematopoietic Cell Transplantation (HCT) Next-generation-sequence (NGS) Minimal Residual Disease (MRD) Negative
This study will evaluate the use of non- TBI (total body irradiation) conditioning for B-ALL patients with low risk of relapse as defined by absence of NGS-MRD (next generation sequencing minimal residual disease) before receiving a hematopoietic cell transplant (HCT). Patients diagnosed with B-ALL who are candidates for HCT will be screened by NGS-MRD on a test of bone marrow done before the HCT. Subjects who are pre-HCT NGS-MRD negative will be eligible to receive a non-TBI conditioning regimen as part of the treatment cohort of the study. Subjects who are pre-HCT NGS-MRD positive will be treated as per treating center standard and will be followed in an observational cohort (HCT center standard of care).
⁃ Any patient with ALL who undergoes Myeloablative HCT including any of the following:
• Patients who are pre-HCT NGS-MRD positive.
• Patients \<1 year old who are pre-HCT NGS-MRD negative.
• Patients who are pre-HCT NGS-MRD negative (CR1/CR2) who received inotuzumab ozogamicin therapy before proceeding to HCT.
• Patients who are pre-HCT NGS-MRD negative and will be receiving haploidentical HCT.
• Patients who are pre-HCT NGS-MRD negative in CR2 with history of CNS relapse.
• Patients who have received blinatumomab, but are \>CR2 prior to HCT.
• Patients who have received CART-T cellular therapy, but are \>CR2 prior to HCT.
• Patients with pre-HCT NGS-MRD negative in ≥ CR3.
• Any T-ALL and MPAL patients undergoing first allogeneic HCT
• Any patient who is pre-HCT NGS-MRD negative and eligible for participation in the treatment arm but family does not consent for treatment arm or treating physician believe it is in the patient best interest not to enroll on the treatment arm
• Pre-HCT NGS-MRD negative
• Age ≥ 1 year and ≤ 25 years
• Disease status: B-ALL in first (CR1) or second remission (CR2)
• No prior allogeneic hematopoietic stem cell transplant.
• Patients in CR1 or CR2 after blinatumomab treatment.
• Patients in CR1 or CR2 after CAR-T cellular therapy.
• 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.
• Able to give informed consent if \> 18 years, or with a legal guardian capable of giving informed consent if \< 18 years.
• Adequate organ function (within 4 weeks of initiation of preparative regimen), defined as:
• Pulmonary: 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 due to age, the criteria are: no evidence of dyspnea at rest and no need for supplemental oxygen.
• Renal: Creatinine clearance or radioisotope GFR ≥ 60 mL/min/1.73 m2 or a serum creatinine based on age/gender.
• Cardiac: 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.
• Hepatic: SGOT (AST) or SGPT (ALT) \< 5 x upper limit of normal (ULN) for age. Conjugated bilirubin \< 2.5 mg/dL, unless attributable to Gilbert's Syndrome.