Depleting specific immune cells in stem cell transplants for blood cancers

Alpha/Beta T Cell and CD19+ B Cell Depletion in Allogeneic Stem Cell Transplantation in Patients With Malignant Diseases

This study is testing if removing certain immune cells during stem cell transplants can help children and young adults with blood cancers have better outcomes and fewer complications.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 6 Months to 39 Years
• Sex: All
• Sponsor: University of Florida (Academic / other)
• Locations: 1 site (Gainesville, Florida)
• Trial ID: NCT05800210 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of depleting alpha/beta T-cells and CD19+ B-cells in allogeneic stem cell transplantation for patients with various hematologic malignancies, including acute lymphoblastic leukemia and acute myeloid leukemia. Participants will undergo a stem cell transplant using cells processed with the Miltenyi CliniMACS Prodigy® system to enhance outcomes. The trial focuses on children, adolescents, and young adults aged 6 months to 39 years who have specific high-risk conditions. The goal is to improve transplant success rates and reduce complications associated with the procedure.

Who should consider this trial

Good fit: Ideal candidates include children, adolescents, and young adults aged 6 months to 39 years with high-risk acute lymphoblastic leukemia, acute myeloid leukemia, or other specified hematologic malignancies.

Not a fit: Patients with low-risk forms of the specified cancers or those outside the age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved transplant outcomes and reduced incidence of graft-versus-host disease in patients with blood cancers.

How similar studies have performed: Other studies have shown promise in similar approaches to stem cell transplantation, suggesting potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

A. Children, Adolescents, Young adults (ages 6 months to ≤39 years) with the following diseases may be eligible:

i. ALL

1. ALL high risk including one or more of the following: (t(9;22) or 11q23 chromosomal abnormality, primary induction failure (≤15% blasts at time of registration), mixed phenotype acute leukemia (MPAL), persistent MRD (≥0.01% by flow or persistent abnormal karyotype detected by cytogenetics) or hypodiploidy (≤44 chromosomes)) in first remission
2. ALL in second remission and beyond

ii. AML

1. History of AML induction/reinduction Failure (≤15% blasts at time of registration)
2. AML in CR1 with poor cytogenetics (i.e., 12p, 5a, -7, FLT3 mutation/duplication, t(9;11) and others)
3. AML with persistent minimal residual disease (MRD) in CR1(≥0.01% on flow or persistent abnormal karyotype detected by cytogenetics)
4. AML CR2 or beyond
5. AML in refractory relapse but ≤15% bone marrow leukemia blasts
6. Therapy-related AML

iii. Juvenile MyeloMonocytic Leukemia (JMML)

1. JMML in CR1 without CBL mutation
2. JMML with recurrence of disease with or without CBL mutation
3. JMML CR2 or beyond

iv. Chronic Myeloid Leukemia (CML)

1\. CML in CR with regard to blast crisis

v. High Risk Myelodysplastic syndrome (MDS)

vi. Lymphoma: Hodgkin (HL) or Non-Hodgkin (NHL)

1. HL or NHL with a history of induction failure
2. HL or NHL in PR1 or PR2
3. HL or NHL in CR2 or subsequent remission

B. Subjects must not have more than one active malignancy at the time of enrollment (Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen \[as determined by the treating physician and approved by the PI\] may be included).

C. HLA-matched (5-6/6) sibling donor, matched (8-10/10) unrelated donor available for stem cell donation, haplo-identical related donor (at least one full haplotype must be matched).

D. Karnofsky or Lansky score ≥60% at the time of enrollment. Karnofsky scores must be used for patients \>16 years of age and Lansky scores for patients ≤16 years of age.

E. Adequate organ function (within 4 weeks of initiation of preparative regimen), defined as:

i. Pulmonary: FEV1, FVC, and corrected DLCO must all be ≥ 60% 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.

ii. Renal: Creatinine clearance or radioisotope GFR ≥60 mL/min/1.73 m2 or a serum creatinine based on age/gender

iii. Cardiac: Shortening fraction of ≥ 27% by echocardiogram) or ejection fraction of ≥ 50% by echocardiogram or radionuclide scan (MUGA).

iv. 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.

F. Written informed consent obtained from the subject or guardian and the subject agrees to comply with all the study-related procedures.

G. Subjects of childbearing potential (SOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 8 weeks after the last dose of study drug to minimize the risk of pregnancy.

H. Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 8 weeks following the last dose of study drug.

Exclusion Criteria:

A. Patients with documented uncontrolled infection

B. Patients who have received allogeneic hematopoietic stem cell transplantation within 6 months, unless being done as a boost.

C. Patients with active ≥Grade 2 aGVHD.

D. Demonstrated lack of compliance with medical care.

E. Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 8 weeks after the last dose of study drug.

F. Females who are known to be pregnant or breastfeeding.

G. History of any other disease, metabolic dysfunction, clinical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.

H. Prisoners or subjects who are incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

Where this trial is running

Gainesville, Florida

• University of Florida — Gainesville, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Jordan Milner, MD — University of Florida
• Study coordinator: Beate Greer

Conditions Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndromes; Chronic Myeloid Leukemia; Lymphoma, Non-Hodgkin; Lymphoma, Hodgkin; hematologic malignancy