- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03620058
CART22 Alone or in Combination With huCART19 for ALL
Phase 1 Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells (CART22-65s) Alone and When Co-administered With Humanized Anti-CD19 Chimeric Antigen Receptor Redirected T Cells (huCART19) In Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 1. Patients with relapsed or refractory B cell ALL:
a. Patients with 2nd or greater relapse or refractory to 1st salvage as defined by: i. Recurrent disease in the bone marrow identified morphologically, by immunohistochemistry or by Flow cytometry.
ii. Patients with extramedullary relapse only (no bone marrow involvement) will be eligible if disease response can be assessed radiographically b. Patients with refractory disease as defined by: i. Failure to achieve remission (<5% bone marrow blasts) after 2 cycles of induction chemotherapy ii. Patients that achieve remission but remain MRD+ after ≥2 cycles of induction chemotherapy.
c. Patients with Ph+ ALL are eligible provided they are intolerant to or have failed tyrosine kinase inhibitor therapy.
d. Patients with prior or current history of CNS3 disease* will be eligible only if CNS disease is responsive to therapy.
i. *CNS disease definitions:
- CNS1 - no blasts seen on cytocentrifuge (CNS negative);
- CNS2 - total nucleated cell count <5x106/L, but blasts seen on cytocentrifuge;
CNS3 - total nucleated cell count 5x106/L with blasts on cytocentrifuge and/or signs of CNS leukemia (i.e. cranial nerve palsy).
- 2. For Cohort 1: Documentation of CD22 expression on malignant cells at relapse. For Cohort 2: Documentation of CD22 and/or CD19
3. Adequate vital organ function defined as:
- Creatinine ≤ 1.6 mg/dl
- ALT/AST ≤ 3x upper limit of normal range
- Total or Direct bilirubin ≤ 2.0 mg/dl. If Total bilirubin is ≤2.0, Direct bilirubin does not need to be assessed.
- Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
- 4. Male or female age ≥ 18 years.
- 5. ECOG Performance Status that is either 0 or 1.
- 6. No contraindications for leukapheresis.
- 7. Subjects of reproductive potential must agree to use acceptable birth control methods.
Exclusion Criteria:
- 1. Active hepatitis B or active hepatitis C.
- 2. HIV Infection.
- 3. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
- 4. Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of eligibility confirmation by physician-investigator.
- 5. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
- 6. Planned concurrent treatment with systemic steroids or immunosuppressant medications. Patients may be on a stable low dose of steroids (<10mg equivalent of prednisone) for chronic respiratory conditions or adrenal insufficiency. For additional details regarding use of steroid and immunosuppressant medications.
- 7. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
- 8. Pregnant or nursing (lactating) women.
- 10. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CART22-65s monotherapy
|
Autologous T cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB
|
Experimental: CART22-65s in combination with huCART19
|
Autologous T cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB
Autologous T cells transduced with lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assess the safety of CART22-65s in ALL subjects using the common terminology criteria of adverse events (CTCAE) v5.0.
Time Frame: 15 months
|
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).
|
15 months
|
Assess the safety of combination CART22-65s and huCART19 in relapsed/refractory ALL Subjects using the common terminology criteria of adverse events (CTCAE) v5.0.
Time Frame: 15 months
|
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).
|
15 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor response.
Time Frame: 28 Days
|
Overall Complete Remission Rate (ORR) at Day 28 which includes CR and CR with incomplete blood count recovery (CRi).
|
28 Days
|
Tumor response.
Time Frame: 6 months
|
overall response rate (CR/CRi by or at Month 6) and disease response status at Month 6
|
6 months
|
Tumor response.
Time Frame: 1 Year
|
overall survival (OS)
|
1 Year
|
Tumor response.
Time Frame: 1 Year
|
duration of remission (DOR)
|
1 Year
|
Tumor response.
Time Frame: 1 Year
|
relapse free survival (RFS)
|
1 Year
|
Tumor response.
Time Frame: 1 Year
|
event free survival (EFS)
|
1 Year
|
CAR T cell kinetics
Time Frame: 1 Year
|
Engraftment and persistence in blood by qPCR (or flow cytometry)
|
1 Year
|
CAR T cell kinetics
Time Frame: 1 Year
|
Trafficking to target tissue (bone marrow) or other tissues (cerebral spinal fluid and other tissues if available) as determined by qPCR (or flow cytometry).
|
1 Year
|
Evaluate bioactivity of CAR T cells
Time Frame: 1 Year
|
Measure levels of systemic soluble immune and inflammatory factors by Luminex-based analyses
|
1 Year
|
Determine antigen expression and normal B cell levels in response to CAR T cells
Time Frame: 1 Year
|
Measure CD22, CD19 and B cell levels pre- and post-CAR T cell infusion by flow cytometry
|
1 Year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Noelle Frey, MD, University of Pennsylvania
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
- IRB # 830049; UPCC #12418
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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