Back to resultsAutologous HuCART19 T Cells Manufactured Using the CliniMACS Prodigy Platform for Pediatric B-ALL (huCART19 Prodigy)
Primary Purpose
B Cell Acute Lymphoblastic Leukemia (B-ALL), B Lineage Lymphoblastic Lymphoma
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous Humanized CD19-Directed Chimeric Antigen Receptor T-Cells (huCART19)
Sponsored by
About this trial
This is an interventional treatment trial for B Cell Acute Lymphoblastic Leukemia (B-ALL)
Eligibility Criteria
Inclusion Criteria:
- Signed Informed Informed Consent
Subjects with documented CD19+ ALL or Lly:
- Cohort A: Subjects with relapsed or refractory ALL or Lly
- Cohort B: Subjects with poor response to prior B cell directed engineered cell therapy,
- Subjects with prior or current history of CNS3 disease will be eligible if Central Nervous System (CNS) disease is responsive to therapy (at infusion, must meet criteria in Section 7.6.2).
- Documentation of CD19 tumor expression in bone marrow, peripheral blood, cerebrospinal fluid (CSF), or tumor tissue by flow cytometry. If the subject has received CD19-directed therapy, flow cytometry should be obtained after this therapy to demonstrate CD19 expression.
- Age 0-29 years
- Adequate organ function
- Adequate performance status defined as Lanksy or Karnofsky performance score ≥50
- Subjects of reproductive potential must agree to use acceptable birth control methods.
Exclusion Criteria:
- Active hepatitis B or active hepatitis C
- HIV infection
- Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
- Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
- CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
- Pregnant or nursing (lactating) women.
- Uncontrolled active infection.
Sites / Locations
- Children's Hospital of Philadelphia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dose Escalation Arm
Dose Expansion Arms
Arm Description
The phase 1 dose escalation portion of the trial will use a standard "3+3" design to establish the recommended phase 2 dose of huCART19 cells in patients with subjects with prior treatment with CD19-directed CAR T cells. Two dose escalations of huCART19 are planned for the dose escalation phase.
If at least one dose level of the dose escalation phase is determined to be safe, the phase 2b dose expansion phase of the trial will be opened to enrollment. Subjects will receive the highest dose of huCART19 cells that were determined to be safe in the dose escalation part of the trial. 2 cohorts are planned: Cohort A (relapsed/refractory, CAR T cell naïve) Cohort B (prior treatment with CD19-directed CAR T cells)
Outcomes
Primary Outcome Measures
Safety of huCART19 Administration
The safety of the administering Humanized Cd19-Directed Chimeric Antigen Receptor T-Cells (huCART9) will be measured by the monitoring the frequency and severity of adverse events in patients with advanced or refractory CD19+ hematologic malignancies, including those previously treated with cell therapy.
Efficacy of huCART19 Administration
The efficacy of huCART9 will be measured by the evaluating the overall response rate in patients with advanced or refractory CD19+ hematologic malignancies, including those previously treated with cell therapy.
Secondary Outcome Measures
Manufacturing Feasibility
Manufacturing feasibility will be measured by the percentage of manufactured products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility, or due to tumor contamination.
Safety of huCART19 as measured by ≥ Grade 3 toxicity rate
Safety of huCART19 as measured by ≥ Grade 3 toxicity rate (toxicity that is possibly attributed to huCART19) that is unmanageable, unexpected, and unrelated to chemotherapy.
Anti-tumor response due to huCART19 cell infusions
For subjects with detectable disease, measure anti-tumor response due to huCART19 cell infusions, as defined by the presence of medullary (morphologic or Minimal Residual Disease (MRD-level disease) and/or extramedullary disease at 1-month post-infusion.
Remission Rate
Overall remission rate will be measured by the proportion of treated subjects who achieve complete morphologic remission at Day 28 post huCART19 infusion.
huCART19 cell persistence
huCART 19 cell persistence will be measured by PCR (or flow) analysis of whole blood to detect and quantify survival of huCART19 cells over time.
Event Free Survival
1-year Event-Free Survival (EFS) in subjects with relapsed/refractory B-ALL (Cohort A) and in subjects with poor response to prior B cell directed engineered cell therapy (Cohort B).
Relapse-Free Survival
1-year Relapse-Free Survival (RFS) in subjects with relapsed/refractory B-ALL (Cohort A) and in subjects with poor response to prior B cell directed engineered cell therapy (Cohort B).
Overall Survival
1-year Overall Survival (OS) in subjects with relapsed/refractory B-ALL (Cohort A) and in subjects with poor response to prior B cell directed engineered cell therapy (Cohort B).
Full Information
NCT ID
NCT05480449
First Posted
July 27, 2022
Last Updated
August 28, 2023
Sponsor
Stephan Grupp MD PhD
Collaborators
Children's Hospital of Philadelphia
1. Study Identification
Unique Protocol Identification Number
NCT05480449
Brief Title
Autologous HuCART19 T Cells Manufactured Using the CliniMACS Prodigy Platform for Pediatric B-ALL (huCART19 Prodigy)
Official Title
Phase 1/2b Trial of Autologous Humanized CD19-Directed Chimeric Antigen Receptor T-Cells Manufactured Using the CliniMACS Prodigy Platform for the Treatment of Pediatric B Cell Acute Lymphoblastic Leukemia (B-ALL)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 20, 2022 (Actual)
Primary Completion Date
September 20, 2023 (Anticipated)
Study Completion Date
September 20, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Stephan Grupp MD PhD
Collaborators
Children's Hospital of Philadelphia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will determine the safety and efficacy of moving to a second-generation manufacturing process using the CliniMACS Prodigy platform to manufacture huCART19 cells for patients with B cell Acute Lymphoblastic Leukemia (B-ALL).
Detailed Description
Chimeric Antigen Receptor T-Cells (CAR T) cell therapy has shifted the treatment landscape for pediatric and young adult patients with multiply relapsed and refractory B-ALL (B cell Acute Lymphoblastic Leukemia), however, the manufacturing process remains in its first generation: laborious, time-intensive, and not automated. The time and significant personnel resources in this process can result in patient safety issues - with patients growing sicker, with harder to control leukemias - in the waiting period between T cell collection and completed CAR T cell product manufacture. Use of the CliniMACS Prodigy platform, that allows for semi-automated clinical-scale processing of huCART19 cell products in a functionally closed, sterile system, rapidly, without many of the logistical burdens encountered in the first-generation manufacturing method, can help to surmount these issues. This study will determine the safety and efficacy of moving to a second-generation manufacturing process using the CliniMACS Prodigy platform to manufacture huCART19 cells.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B Cell Acute Lymphoblastic Leukemia (B-ALL), B Lineage Lymphoblastic Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
89 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation Arm
Arm Type
Experimental
Arm Description
The phase 1 dose escalation portion of the trial will use a standard "3+3" design to establish the recommended phase 2 dose of huCART19 cells in patients with subjects with prior treatment with CD19-directed CAR T cells. Two dose escalations of huCART19 are planned for the dose escalation phase.
Arm Title
Dose Expansion Arms
Arm Type
Experimental
Arm Description
If at least one dose level of the dose escalation phase is determined to be safe, the phase 2b dose expansion phase of the trial will be opened to enrollment. Subjects will receive the highest dose of huCART19 cells that were determined to be safe in the dose escalation part of the trial. 2 cohorts are planned:
Cohort A (relapsed/refractory, CAR T cell naïve)
Cohort B (prior treatment with CD19-directed CAR T cells)
Intervention Type
Biological
Intervention Name(s)
Autologous Humanized CD19-Directed Chimeric Antigen Receptor T-Cells (huCART19)
Intervention Description
The investigational agent in this protocol is humanized CART19 cells (huCART19). Autologous T cells will be engineered to express an extracellular single chain antibody (scFv) with specificity for CD19. This will be expected to redirect specificity of the transduced T cells for cells that express CD19, a molecule that is restricted in expression on the surface of the malignant cells and on normal B cells.
Primary Outcome Measure Information:
Title
Safety of huCART19 Administration
Description
The safety of the administering Humanized Cd19-Directed Chimeric Antigen Receptor T-Cells (huCART9) will be measured by the monitoring the frequency and severity of adverse events in patients with advanced or refractory CD19+ hematologic malignancies, including those previously treated with cell therapy.
Time Frame
5 years
Title
Efficacy of huCART19 Administration
Description
The efficacy of huCART9 will be measured by the evaluating the overall response rate in patients with advanced or refractory CD19+ hematologic malignancies, including those previously treated with cell therapy.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Manufacturing Feasibility
Description
Manufacturing feasibility will be measured by the percentage of manufactured products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility, or due to tumor contamination.
Time Frame
5 years
Title
Safety of huCART19 as measured by ≥ Grade 3 toxicity rate
Description
Safety of huCART19 as measured by ≥ Grade 3 toxicity rate (toxicity that is possibly attributed to huCART19) that is unmanageable, unexpected, and unrelated to chemotherapy.
Time Frame
5 years
Title
Anti-tumor response due to huCART19 cell infusions
Description
For subjects with detectable disease, measure anti-tumor response due to huCART19 cell infusions, as defined by the presence of medullary (morphologic or Minimal Residual Disease (MRD-level disease) and/or extramedullary disease at 1-month post-infusion.
Time Frame
5 years
Title
Remission Rate
Description
Overall remission rate will be measured by the proportion of treated subjects who achieve complete morphologic remission at Day 28 post huCART19 infusion.
Time Frame
5 years
Title
huCART19 cell persistence
Description
huCART 19 cell persistence will be measured by PCR (or flow) analysis of whole blood to detect and quantify survival of huCART19 cells over time.
Time Frame
5 years
Title
Event Free Survival
Description
1-year Event-Free Survival (EFS) in subjects with relapsed/refractory B-ALL (Cohort A) and in subjects with poor response to prior B cell directed engineered cell therapy (Cohort B).
Time Frame
5 years
Title
Relapse-Free Survival
Description
1-year Relapse-Free Survival (RFS) in subjects with relapsed/refractory B-ALL (Cohort A) and in subjects with poor response to prior B cell directed engineered cell therapy (Cohort B).
Time Frame
5 years
Title
Overall Survival
Description
1-year Overall Survival (OS) in subjects with relapsed/refractory B-ALL (Cohort A) and in subjects with poor response to prior B cell directed engineered cell therapy (Cohort B).
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
29 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed Informed Informed Consent
Subjects with documented CD19+ ALL or Lly:
Cohort A: Subjects with relapsed or refractory ALL or Lly
Cohort B: Subjects with poor response to prior B cell directed engineered cell therapy,
Subjects with prior or current history of CNS3 disease will be eligible if Central Nervous System (CNS) disease is responsive to therapy (at infusion, must meet criteria in Section 7.6.2).
Documentation of CD19 tumor expression in bone marrow, peripheral blood, cerebrospinal fluid (CSF), or tumor tissue by flow cytometry. If the subject has received CD19-directed therapy, flow cytometry should be obtained after this therapy to demonstrate CD19 expression.
Age 0-29 years
Adequate organ function
Adequate performance status defined as Lanksy or Karnofsky performance score ≥50
Subjects of reproductive potential must agree to use acceptable birth control methods.
Exclusion Criteria:
Active hepatitis B or active hepatitis C
HIV infection
Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
Pregnant or nursing (lactating) women.
Uncontrolled active infection.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allison Barz Leahy, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Stephan Grupp, MD,PhD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Autologous HuCART19 T Cells Manufactured Using the CliniMACS Prodigy Platform for Pediatric B-ALL (huCART19 Prodigy)
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