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

NCT04249830 | Recruiting DMC FDA Device

• 2 other identifiers: IRB-53822BMT 361 - Alpha Beta IDE
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the CliniMACS® TCRαβ-Biotin System and CliniMACS® CD19 is to improve the safety and efficacy of allogeneic HLA-partially matched related or unrelated donors HSCT when no matched donors are available, to treat malignant and nonmalignant disorders for which HSCT is the recommended best available therapy. Initially this device will be used in a single-center, open-label, single-arm, phase II clinical trial to evaluate the efficacy of haploidentical PBSC grafts depleted of TCRα/β+ and CD19+ cells using the CliniMACS® TCRαβ/CD19 System in children and adults with hematological and non-hematological malignancies.

Conditions

Hematologic Diseases

Outcome Measures

Primary Outcomes (1)

• Number of participants with grade II-IV acute GvHD after HSCT

  Through Day 100 after HSCT

Secondary Outcomes (5)

• Leukemia-free survival after HSCT

  1 and 2 years after HSCT

• Number of participants with secondary graft failure at after HSCT

  1 and 2 year after HSCT

• Number of participants with grade III-IV acute GvHD after HSCT

  Through Day 100 after HSCT

• Incidence rate of primary graft failure after HSCT

  Day 42 after HSCT

• Incidence of moderate and severe chronic GvHD after HSCT

  1 year after HSCT

Study Arms (3)

Stem Cell Transplant -Malignant

EXPERIMENTAL

The participant with a malignancy will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. Participants will be followed for outcomes for two years.

Biological: Allogeneic Stem Cell Transplant; Device: CliniMACS TCR α/β Reagent Kit and CliniMACS CD19

Stem Cell Transplant - Non-Malignant

EXPERIMENTAL

The participant with a non-malignant disease will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. Participants will be followed for outcomes for two years.

Biological: Allogeneic Stem Cell Transplant; Device: CliniMACS TCR α/β Reagent Kit and CliniMACS CD19

Stem Cell Transplant - Compassionate

OTHER

Patients with malignant or non-malignant disorders who do not qualify for experimental arms but who may still benefit from participation in this study may be enrolled in this arm.

Biological: Allogeneic Stem Cell Transplant; Device: CliniMACS TCR α/β Reagent Kit and CliniMACS CD19

Interventions

Allogeneic Stem Cell Transplant BIOLOGICAL

The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.

Stem Cell Transplant - Compassionate; Stem Cell Transplant - Non-Malignant; Stem Cell Transplant -Malignant

CliniMACS TCR α/β Reagent Kit and CliniMACS CD19 DEVICE

The CliniMACS™system can be used to selectively enrich or reduce specific cell populations based on the magnetic cell selection (MACS) technology developed by Miltenyi Biotec. Cell mixtures can be separated in a magnetic field using one or more immunomagnetic- labeled antibodies specific for the cell types of interest (e.g.TCR αβ+ T cells and CD19+ B cells from HPC(A) products).

Stem Cell Transplant - Compassionate; Stem Cell Transplant - Non-Malignant; Stem Cell Transplant -Malignant

Eligibility Criteria

• Age: 1 Month - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age \< 60 years and \> 1 month;
• Life expectancy \> 10 weeks;
• Patients deemed eligible for allogeneic HSCT per institutional guidelines;
• 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;
• A minimum genotypic identical match of 5/10 is required;
• 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;
• 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.
• 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
• 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.

You may not qualify if:

• Pregnant or lactating females;
• Has received a prior allogenic HSCT;
• Secondary MDS or AML or treatment related MDS or AML;
• Dysfunction of liver (ALT/AST \> 10 times upper normal value, or direct bilirubin \> 3 times upper normal value),
• Serum creatinine \> 1.5 times ULN (for patients not on dialysis) or unmanageable dysfunction of renal function while undergoing dialysis (for patients on dialysis);
• Severe cardiovascular disease (congestive heart failure or left ventricular ejection fraction \< 30%);
• Current active infectious disease (including positive HIV serology or viral RNA);
• Serious concurrent uncontrolled medical disorders;
• Lack of patient's/parents'/guardian's informed consent;
• Any severe concurrent disease which, in the judgement of the PI, would place the patient at increased risk during participation in the study.

Sponsors & Collaborators

• Alice Bertaina: lead

Study Sites (1)

Lucile Packard Children's Hospital

Palo Alto, California, 94306, United States

RECRUITING

MeSH Terms

Conditions

Hematologic Diseases

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Study Officials

• David Shyr, MD

  Clinical Associate Professor, Pediatrics, Stem Cell Transplantation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: January 29, 2020
• First Posted: January 31, 2020
• Study Start: February 1, 2020
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)