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
Investigating Non-TBI Conditioning for B-cell Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Cell Transplant
Brief description of study.
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).
Detailed description of study
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).
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: B-cell Acute Lymphoblastic Leukemia
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Age: 1 years - 25 years
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Gender: All
Inclusion Criteria
Observational Arm:
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
Treatment Arm:
Pre-HCT NGS-MRD negative
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.
Adequate organ function
Exclusion Criteria
CR2: exclude patients with history of CNS relapse (i.e. in CR2 with history of CNS isolated or combined relapse; CNS 2 will also be considered as CNS 3 for this purpose) from the treatment arm of study (can be enrolled on the observational arm).
Patients who have received inotuzumab treatment prior to allogeneic HCT are NOT eligible for the study treatment arm. Inotuzumab treatment may increase the risk of VOD/SOS for any allogeneic HCT recipient, but could potentiate the risk for with busulfan-based myeloablation (study-directed non-TBI conditioning). All inotuzumab-treated patients are eligible for the observational arm (HCT center standard of care).
Patients receiving non-myeloablative conditioning are not allowed on the observational arm (reduced toxicity conditioning with Flu/Mel/Thio is allowed on the observational arm).
Pregnant or lactating females are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants.
Patients with HIV or uncontrolled fungal, bacterial or viral infections are excluded. Patients with history of fungal disease during induction therapy may proceed if they have a significant response to antifungal therapy with no evidence or minimal evidence of non-progressive disease remaining by CT evaluation.
Patients with active CNS leukemia or any other active site of extramedullary disease at the time of enrollment are not permitted.
T-ALL and MPAL patients are only allowed on the observational arm.
Patients with genetic disorders (generally marrow failure syndromes) prone to secondary AML/ALL with known poor outcome are not eligible (Fanconi Anemia, Kostmann Syndrome, Dyskeratosis Congenita, etc).
This study investigates the use of non-total body irradiation (non-TBI) conditioning for patients with B-cell Acute Lymphoblastic Leukemia (B-ALL) who are at low risk of relapse. B-ALL is a type of cancer that affects the blood and bone marrow. The study focuses on patients who do not have minimal residual disease (MRD) as detected by next-generation sequencing (NGS) before they receive a hematopoietic cell transplant (HCT).
Participants will be divided into two study arms. Those who are NGS-MRD negative before HCT will receive a non-TBI conditioning regimen. This means they will undergo a treatment that prepares their body for the transplant without using total body irradiation. Those who are NGS-MRD positive will be treated according to the standard care of their treatment center and will be observed as part of the study.
- Who can participate: Patients with B-ALL in their first or second remission who are NGS-MRD negative and have not had a prior allogeneic stem cell transplant may participate. They must also have adequate organ function and no history of CNS relapse in their second remission.
- Study details: Participants in the treatment arm will receive non-TBI conditioning before their hematopoietic cell transplant. This conditioning prepares the body for the transplant without using total body irradiation. In the observational arm, patients will be treated according to the standard care of their treatment center. A placebo is not applicable in this study.
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