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

J
Jodi Skiles

Primary Investigator

Enrolling By Invitation
1-25 years
All
Phase 2
15 participants needed
2 Locations

Brief description of study

What is the purpose of this 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). The primary purpose of this study is to evaluate whether or not patients with NGS-MRD negative result before HCT will have the same or similar medical outcome if they do not receive total body irradiation (TBI) before HCT.

Only eligible patients that have been referred by a physician and seen by section of Pediatric Hematology/Oncology staff will be invited to participate in the clinical trial.

THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic.

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

What will happen during the 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).

All subjects will participate in the NGS-MRD Testing part of this study.  In this part of the study, the subject will have bone marrow and/or blood samples collected for NGS-MRD testing for research purposes at the following timepoints.  Research samples will be collected at the same time as when bone marrow and blood tests are performed for the subject’s routine care.  
  • Pre-HCT bone marrow and blood will be collected .
  • After HCT:
  • Day 42  bone marrow and blood
  • Day 100  bone marrow and blood
  • Day 180  blood only
  • Day 270  blood only
  • Day 365 (1 year)  bone marrow and blood

For B-ALL patients, the subject’s transplant doctor will tell them if their NGS-MRD test is negative before their transplant and if the subject qualifies for the Non-TBI Arm.  

For the treatment arm of the study (non-TBI) the following will occur:
  • If the subject’s NGS-MRD testing was reported back to their doctor as negative, they will be offered the treatment arm of the study. If the subject qualifies, their transplant doctor will discuss the Non-TBI Arm separately with them.  The subject’s transplant doctor will also tell them if the subject does not qualify for the Non-TBI Arm.
  • The subjects will NOT receive total body irradiation (TBI) prior to receiving their transplant.  
  • The subject will be given a conditioning regimen for 12 days before their transplant. This conditioning regimen will be chosen by transplant doctor.  For the drugs to be given, a central line will be placed and is standard of care for transplant patients. 
  • Also before transplant tests will be done that are standard of care, they include, complete blood count, serum chemistries, estimated creatinine clearance, pregnancy test, echocardiogram, pulmonary function tests, peripheral blood and bone marrow chimerism, bone marrow and blood collection to test minimal residual disease, diagnostic lumbar puncture, history and physical exam, and  Karnofsky score.   
  • After transplant, tests will be performed that are standard of care and they include GVHD grading and immune reconstitution studies. 
  • Then the subject’s transplant will be done per standard of care.  
  • The subject will be followed for up to 5 years and data collection will be submitted to sponsor.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: B-cell Acute Lymphoblastic Leukemia, Riley
  • Age: Between 1 Years - 25 Years
  • 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).

Updated on 14 Sep 2024. Study ID: 1811410126 (PHO-PBMTC-ENDRAD)
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