Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Young Adults

Launched by ALICE BERTAINA · Jan 29, 2020

Keywords

ClinConnect Summary

This clinical trial is exploring a new approach to stem cell transplants for children and young adults with serious blood-related diseases, such as certain types of cancer and other conditions. The goal of the study is to safely use stem cells from partially matched donors, which could be helpful for patients who do not have a fully matched donor available. The researchers will use a special device to remove certain types of cells from the donor's stem cells to improve the success and safety of the transplant.

To participate in this study, patients must be between 1 month and 60 years old and have a life-threatening condition that could benefit from a stem cell transplant. They need to have a donor who is at least a partial genetic match. Participants will be monitored closely throughout the trial, and they will need to give written consent to join. It's important to note that some people, like those who are pregnant or have certain serious health issues, are not eligible to participate. If you or someone you know may qualify for this trial, it could offer a new opportunity for treatment.

Gender

ALL

Eligibility criteria

• Inclusion Criteria for Cohort M and Cohort NM:
• • 1. Age \< 60 years and \> 1 month;
• • 2. Life expectancy \> 10 weeks;
• • 3. Patients deemed eligible for allogeneic HSCT per institutional guidelines;
• • 4. Patients with life-threatening hematological malignancies and non-malignant disorders that could benefit from HSCT;
• • a. For malignant patients: i. High-risk acute lymphoblastic leukemia (ALL) in 1st complete remission (CR), ALL in 2nd CR; or ii. High-risk acute myeloid leukemia (AML) in 1st CR, AML in 2nd CR; or iii. Childhood Myelodysplastic Syndrome (MDS) with low blasts (cMDS-LB) or Childhood MDS with increased blasts (cMDS-IB); or iv. Juvenile myelomonocytic leukemia (JMML); or v. Mixed-phenotype acute leukemia (MPAL); or vi. Non-Hodgkin lymphomas in 2nd CR; or vii. Other hematologic malignancies in 1st or 2nd CR eligible for stem cell transplantation per institutional standard b. Patients with non-malignant disorders receiving first HSCT: i. using mis-matched donors, due to the absence of suitable HLA identical sibling or HLA phenotypically identical relative; or ii. whose disease put them at increased risk of graft rejection or GvHD (e.g., Fanconi Anemia, STAT1 gain of function) and therefore can benefit from receiving alpha beta depleted HSCT using as a donor either an HLA identical sibling or an HLA phenotypically identical (10/10 matched) donor;
• • 5. A minimum genotypic identical match of 5/10 is required;
• • 6. The donor and recipient must be identical, as determined by high resolution typing, in at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-C, HLA-DQB1 and HLA-DRB1;
• • 7. Lansky/Karnofsky score \> 50; the Karnofsky Scale will be used in subjects ≥ 16 years of age, and the Lansky Scale will be used for those \< 16 years of age.
• • 8. All subjects ≥ 18 years of age must be able to give informed consent or adults lacking capacity to consent must have a legally authorized representative (LAR) available to provide consent. For subjects \<18 years old their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric subjects will be included in age appropriate discussion and written assent will be obtained for those \> 7 years of age, when appropriate
• • 9. Male and female subjects of childbearing potential must agree to use an effective means of birth control to avoid pregnancy throughout the transplant procedure, while on immunosuppression, and if the subject experiences any chronic GvHD.
• Exclusion Criteria for Cohort M and Cohort NM:
• • 1. Pregnant or lactating females;
• • 2. Has received a prior allogenic HSCT;
• • 3. Secondary MDS or AML or treatment related MDS or AML;
• • 4. Dysfunction of liver (ALT/AST \> 10 times upper normal value, or direct bilirubin \> 3 times upper normal value),
• • 5. Serum creatinine \> 1.5 times ULN (for patients not on dialysis) or unmanageable dysfunction of renal function while undergoing dialysis (for patients on dialysis);
• • 6. Severe cardiovascular disease (congestive heart failure or left ventricular ejection fraction \< 30%);
• • 7. Current active infectious disease (including positive HIV serology or viral RNA);
• • 8. Serious concurrent uncontrolled medical disorders;
• • 9. Lack of patient's/parents'/guardian's informed consent;
• • 10. Any severe concurrent disease which, in the judgement of the PI, would place the patient at increased risk during participation in the study.