Back to resultsStem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Adults With T-allo10 Cells Addback
Primary Purpose
Hematologic Diseases
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Stem Cell Transplant
CliniMACS Prodigy System
T-allo10 cells addback
Sponsored by
About this trial
This is an interventional treatment trial for Hematologic Diseases
Eligibility Criteria
Inclusion Criteria prior to enrollment:
- 1. Age > 1 months (with minimum weight of 10 Kg) and < 45 years.
- 2. Patients deemed eligible for allogeneic HSCT under the originating study, NCT 04249830
3. Patients with life-threatening hematological malignancies for which HSCT has been recommended:
- High-risk ALL in 1st CR, ALL in 2nd or subsequent CR;
- High-risk AML in 1st CR, AML in 2nd or subsequent CR;
- Myelodysplastic syndrome;
- JMML (Juvenile myelomonocytic leukemia);
- Non-Hodgkin lymphomas in 2nd or subsequent CR;
- Other hematologic malignancies eligible for stem cell transplantation per institutional standard.
- 4. All subjects ≥ 18 years of age must be able to give informed consent, or adults lacking capacity to consent must have a LAR available to provide consent. For subjects <18 years old their LAR (i.e. parent or guardian) must give informed consent. Pediatric subjects will be included in age appropriate discussion and verbal assent will be obtained for those > 7 years of age, when appropriate.
Inclusion criteria prior to T-allo10 infusion:
- Patient already received αβdepleted-HSCT and has myeloid engraftment.
- Absence of active grade II aGvHD requiring >0.5 mg/Kg of steroids or any diagnosis of grade III/IVaGvHD.
Exclusion Criteria prior to MNC collection for Tallo-10 manufacturing.:
- Not eligible to receive HSCT on NCT04249830
- Received another investigational agent within 30 days of enrollment.
- Pregnancy (positive serum or urine beta-HCG) within 7 days of MNC donation.
- Patient or donor is not willing or able to undergo an additional non-mobilized apheresis for collection of MNC prior to donation of cells for participation in NCT04249830.
Sites / Locations
- Lucile Packard Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental: Stem Cell Transplant
Arm Description
The participant will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. The participant's cells will then be manipulated via a T-allo10 cell addback. Participants will be followed for outcomes for two years.
Outcomes
Primary Outcome Measures
Number of participants with myeloid engraftment after T-allo10
Number of participants without grade II aGvHD requiring steroids after T-allo10
Number of participants without grade III/IV aGvHD after T-allo10
Number of participants with absence of dose-limiting toxicity (DLT) 28 days following the infusion of T-allo10 given at the recommended phase 2 dose (RP2D)
Number of participants who reach immune reconstitution (IR) threshold
IR (a surrogate of reduced risk of leukemia recurrence) is defined reaching the threshold of 50CD3+CD4+T-cells/µl by Day+60(+/-10days).
Secondary Outcome Measures
Number of participants with ≥grade 3 adverse event related to T-allo10 infusion
Number of participants with grade II-IV aGvHD
Number of participants with grade III-IV aGvHD
Number of participants with cGvHD
Leukemia-free survival
Leukemia-free survival defined as at the time of enrollment to disease relapse or death from any cause.
Number of participants with disease relapse
Disease relapse is defined as the return of signs and symptoms of a disease after a remission.
Non-relapse mortality
Non-relapse mortality
Full Information
NCT ID
NCT04640987
First Posted
November 17, 2020
Last Updated
March 25, 2022
Sponsor
Roncarolo, Maria Grazia, MD
Collaborators
California Institute for Regenerative Medicine (CIRM)
1. Study Identification
Unique Protocol Identification Number
NCT04640987
Brief Title
Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Adults With T-allo10 Cells Addback
Official Title
Phase 1/1b Study of T-allo10 Infusion After HLA-Partially Matched Related or Unrelated TCR αβ+ T-cell/ CD19+ B-cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation (αβ Depleted-HSCT) in Children and Young Adults Affected by Hematologic Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 20, 2020 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Roncarolo, Maria Grazia, MD
Collaborators
California Institute for Regenerative Medicine (CIRM)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine the safety of a cell therapy, T-allo10, after αβdepleted-HSCT in the hopes that it will boost the adaptive immune reconstitution of the patient while sparing the risk of developing severe Graft-versus-Host Disease (GvHD).
The primary objective of Phase 1 is to determine the recommended Phase 2 dose (RP2D) administered after infusion of αβdepleted-HSCT in children and young adults with hematologic malignancies.
A Phase 1b extension will occur after dose escalation, enrolling at the RP2D for the T-allo10 cells determined in the Phase 1 portion to evaluate the safety and efficacy of infusion of T-allo10 after receipt of αβdepleted-HSCT. Additionally, Phase 1b aims to explore improvements in immune reconstitution.
All participants on this study must be enrolled on another study: NCT04249830
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental: Stem Cell Transplant
Arm Type
Experimental
Arm Description
The participant will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. The participant's cells will then be manipulated via a T-allo10 cell addback. Participants will be followed for outcomes for two years.
Intervention Type
Biological
Intervention Name(s)
Allogeneic Stem Cell Transplant
Intervention Description
The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.
Intervention Type
Device
Intervention Name(s)
CliniMACS Prodigy System
Intervention Description
Device used for production of T-allo10 cells.
Intervention Type
Drug
Intervention Name(s)
T-allo10 cells addback
Intervention Description
T-allo10 cells are made by manipulating the participant's stem cell donor's white blood cells (CD4+ T cells) in the presence of their (participant's) CD14+ monocytes.
Primary Outcome Measure Information:
Title
Number of participants with myeloid engraftment after T-allo10
Time Frame
Through day 35 (+/- 7 days) after αβdepleted-HSCT
Title
Number of participants without grade II aGvHD requiring steroids after T-allo10
Time Frame
Through day 35 (+/- 7 days) after αβdepleted-HSCT
Title
Number of participants without grade III/IV aGvHD after T-allo10
Time Frame
Through day 35 (+/- 7 days) after αβdepleted-HSCT
Title
Number of participants with absence of dose-limiting toxicity (DLT) 28 days following the infusion of T-allo10 given at the recommended phase 2 dose (RP2D)
Time Frame
Assessed at 28 days (after infusion of T-allo10)
Title
Number of participants who reach immune reconstitution (IR) threshold
Description
IR (a surrogate of reduced risk of leukemia recurrence) is defined reaching the threshold of 50CD3+CD4+T-cells/µl by Day+60(+/-10days).
Time Frame
Through Day 60 (+/- 10 days) after infusion of T-allo10
Secondary Outcome Measure Information:
Title
Number of participants with ≥grade 3 adverse event related to T-allo10 infusion
Time Frame
Through 1 year after αβdepleted-HSCT
Title
Number of participants with grade II-IV aGvHD
Time Frame
Assessed at day 90 after αβdepleted-HSCT
Title
Number of participants with grade III-IV aGvHD
Time Frame
Assessed at day 180 after αβdepleted-HSCT
Title
Number of participants with cGvHD
Time Frame
Assessed at 1 year after αβdepleted-HSCT
Title
Leukemia-free survival
Description
Leukemia-free survival defined as at the time of enrollment to disease relapse or death from any cause.
Time Frame
Assessed at 1 year after αβdepleted-HSCT
Title
Number of participants with disease relapse
Description
Disease relapse is defined as the return of signs and symptoms of a disease after a remission.
Time Frame
Assessed at 1 year after αβdepleted-HSCT
Title
Non-relapse mortality
Time Frame
Assessed at Day 90 after αβdepleted-HSCT
Title
Non-relapse mortality
Time Frame
Assessed at 1 year after αβdepleted-HSCT
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria prior to enrollment:
1. Age > 1 months (with minimum weight of 10 Kg) and < 45 years.
2. Patients deemed eligible for allogeneic HSCT under the originating study, NCT 04249830
3. Patients with life-threatening hematological malignancies for which HSCT has been recommended:
High-risk ALL in 1st CR, ALL in 2nd or subsequent CR;
High-risk AML in 1st CR, AML in 2nd or subsequent CR;
Myelodysplastic syndrome;
JMML (Juvenile myelomonocytic leukemia);
Non-Hodgkin lymphomas in 2nd or subsequent CR;
Other hematologic malignancies eligible for stem cell transplantation per institutional standard.
4. All subjects ≥ 18 years of age must be able to give informed consent, or adults lacking capacity to consent must have a LAR available to provide consent. For subjects <18 years old their LAR (i.e. parent or guardian) must give informed consent. Pediatric subjects will be included in age appropriate discussion and verbal assent will be obtained for those > 7 years of age, when appropriate.
Inclusion criteria prior to T-allo10 infusion:
Patient already received αβdepleted-HSCT and has myeloid engraftment.
Absence of active grade II aGvHD requiring >0.5 mg/Kg of steroids or any diagnosis of grade III/IVaGvHD.
Exclusion Criteria prior to MNC collection for Tallo-10 manufacturing.:
Not eligible to receive HSCT on NCT04249830
Received another investigational agent within 30 days of enrollment.
Pregnancy (positive serum or urine beta-HCG) within 7 days of MNC donation.
Patient or donor is not willing or able to undergo an additional non-mobilized apheresis for collection of MNC prior to donation of cells for participation in NCT04249830.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alice Bertaina, MD, PhD
Organizational Affiliation
Associate Professor of Pediatrics, Stem Cell Transplantation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lucile Packard Children's Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Natalie Pukesh
Phone
650-724-4622
Email
scgt_clinical_trials_office@lists.stanford.edu
First Name & Middle Initial & Last Name & Degree
Rosa Bacchetta, MD
First Name & Middle Initial & Last Name & Degree
David Shyr, MD
First Name & Middle Initial & Last Name & Degree
Rajni Agarwal, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Adults With T-allo10 Cells Addback
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