- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03792633
Study of huCART19 for Very High-Risk (VHR) Subsets of Pediatric B-ALL
Phase 2 Study of Humanized CD19-directed Chimeric Antigen Receptor-modified T Cells (huCART19) for Very High-Risk Subsets of B Cell Acute Lymphoblastic Leukemia (B-ALL)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Mia Benson-Smith
- Phone Number: 267-426-0762
- Email: oncointake@email.chop.edu
Study Contact Backup
- Name: Claire White
- Email: whiteC3@email.chop.edu
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Pennsylvania
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Signed informed consent form must be obtained.
Relapsed or refractory B-cell ALL:
a. Cohort A: Patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL who meet one of the following criteria:
i. Newly diagnosed NCI HR B-ALL with induction failure: M3 marrow (>25% blasts) at end of induction OR
ii. First marrow relapse of B-ALL at < 36 months from diagnosis OR iii. 2nd or greater relapse OR
iv. Any relapse after allogeneic HSCT and ≥ 4 months from SCT at enrollment OR
v. Refractory disease defined as having not achieved an MRD-negative and/or CSF-negative CR after ≥ 2 chemotherapy regimens/cycles of frontline therapy or 1 cycle of reinduction therapy for patients in first relapse OR
vi. Ineligible for allogeneic SCT because of:
1. Comorbid disease 2. Other contraindications to allogeneic SCT conditioning regimen 3. Lack of suitable donor 4. Prior SCT 5. Declines allogeneic SCT as the therapeutic option after documented discussion, with expected outcomes, about the role of SCT with a BMT physician not part of the study team b. Cohort B: Patients previously treated with B cell directed engineered cell therapy who meet one of the following criteria: i. partial response or no response to prior cell therapy ii. CD19+ relapse after prior cell therapy iii. demonstrated early (≤6 months from infusion) B cell recovery suggesting loss of engineered cells c. Patients with prior or current history of CNS3 disease will be eligible if CNS disease is responsive to therapy (at infusion, must meet criteria in Section 5.3) 3. Documentation of CD19 tumor expression in bone marrow, peripheral blood, CSF, or tumor tissue by flow cytometry at relapse (or a recent sample in the case of refractory disease). If the patient has received CD19-directed therapy, then the flow cytometry should be obtained after this therapy to show CD19 expression.
4. Adequate organ function defined as:
- A serum creatinine based on age/gender 4
- ALT≤ 500 U/L
- Bilirubin ≤2.0 mg/dl
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, < Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the treating investigator
Left Ventricular Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO, or adequate ventricular function documented by a scan or a cardiologist.
5. Age 3 months to 29 years. 6. Adequate performance status (Lansky or Karnofsky score ≥50). 7. 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.
- CNS3 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.
- Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS or neurotoxicity.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Newly Diagnosed VHR B-ALL or High-Risk Relapse of B
|
huCART19 infusion
Other Names:
|
Experimental: Poor Response to Prior B Cell Directed Engineered cell therapy
|
huCART19 infusion
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
1-year Event-Free Survival in patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL
Time Frame: 1 year
|
1 year
|
1-year Event-Free Survival in patients with poor response to prior B cell directed engineered cell therapy
Time Frame: 1 year
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Remission Rate (Cohort A)
Time Frame: 28 Days
|
Overall remission rate as determined by the response at day 28, computed as the proportion of subjects with CR or Cri, in patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL.
|
28 Days
|
Overall Remission Rate (Cohort B)
Time Frame: 28 Days
|
Overall remission rate as determined by the response at day 28, computed as the proportion of subjects with CR or Cri, in patients with poor response to prior B cell directed engineered cell therapy.
|
28 Days
|
2-year Event-Free Survival in patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL (cohort A).
Time Frame: 2 years
|
2 years
|
|
2-year Event-Free Survival in patients with poor response to prior B cell directed engineered cell therapy (cohort B)
Time Frame: 2 years
|
2 years
|
|
2-year Relapse-Free Survival in patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL (cohort A).
Time Frame: 2 years
|
2 years
|
|
2-year Relapse-Free Survival in patients with poor response to prior B cell directed engineered cell therapy (cohort B)
Time Frame: 2 years
|
2 years
|
|
Frequency and severity of adverse events
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Shannon Maude, MD, PhD, Children's Hospital of Philadelphia
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 831916
- 18CT014 (Other Identifier: CHOP)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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