CART22 Alone or in Combination With huCART19 for ALL
Study Details
Study Description
Brief Summary
This is a single center, open-label, phase 1 study to determine the safety and feasibility of infusing CART22-65s with or without huCART19 after administration of lymphodepleting chemotherapy in adult patients with relapsed or refractory B-ALL.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CART22-65s monotherapy
|
Biological: CART22-65s cells
Autologous T cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB
|
| Experimental: CART22-65s in combination with huCART19
|
Biological: CART22-65s cells
Autologous T cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB
Biological: huCART19 Cells
Autologous T cells transduced with lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB
|
Outcome Measures
Primary Outcome Measures
- Assess the safety of CART22-65s in ALL subjects using the common terminology criteria of adverse events (CTCAE) v5.0. [15 months]
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).
- 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. [15 months]
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).
Secondary Outcome Measures
- Tumor response. [28 Days]
Overall Complete Remission Rate (ORR) at Day 28 which includes CR and CR with incomplete blood count recovery (CRi).
- Tumor response. [6 months]
overall response rate (CR/CRi by or at Month 6) and disease response status at Month 6
- Tumor response. [1 Year]
overall survival (OS)
- Tumor response. [1 Year]
duration of remission (DOR)
- Tumor response. [1 Year]
relapse free survival (RFS)
- Tumor response. [1 Year]
event free survival (EFS)
- CAR T cell kinetics [1 Year]
Engraftment and persistence in blood by qPCR (or flow cytometry)
- CAR T cell kinetics [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).
- Evaluate bioactivity of CAR T cells [1 Year]
Measure levels of systemic soluble immune and inflammatory factors by Luminex-based analyses
- Determine antigen expression and normal B cell levels in response to CAR T cells [1 Year]
Measure CD22, CD19 and B cell levels pre- and post-CAR T cell infusion by flow cytometry
Eligibility Criteria
Criteria
Inclusion Criteria:
-
- Patients with relapsed or refractory B cell ALL:
- 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.
- 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.
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Patients with Ph+ ALL are eligible provided they are intolerant to or have failed tyrosine kinase inhibitor therapy.
-
Patients with prior or current history of CNS3 disease* will be eligible only if CNS disease is responsive to therapy.
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*CNS disease definitions:
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CNS1 - no blasts seen on cytocentrifuge (CNS negative);
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CNS2 - total nucleated cell count <5x106/L, but blasts seen on cytocentrifuge;
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CNS3 - total nucleated cell count 5x106/L with blasts on cytocentrifuge and/or signs of CNS leukemia (i.e. cranial nerve palsy).
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- For Cohort 1: Documentation of CD22 expression on malignant cells at relapse. For Cohort 2: Documentation of CD22 and/or CD19
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- Adequate vital organ function defined as:
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Creatinine ≤ 1.6 mg/dl
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ALT/AST ≤ 3x upper limit of normal range
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Total or Direct bilirubin ≤ 2.0 mg/dl. If Total bilirubin is ≤2.0, Direct bilirubin does not need to be assessed.
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Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
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- Male or female age ≥ 18 years.
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- ECOG Performance Status that is either 0 or 1.
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- No contraindications for leukapheresis.
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- Subjects of reproductive potential must agree to use acceptable birth control methods.
Exclusion Criteria:
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- Active hepatitis B or active hepatitis C.
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- HIV Infection.
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- Class III/IV cardiovascular disability according to the New York Heart Association Classification.
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- Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of eligibility confirmation by physician-investigator.
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- Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
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- 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.
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- CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
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- Pregnant or nursing (lactating) women.
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- Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- University of Pennsylvania
Investigators
- Principal Investigator: Noelle Frey, MD, University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB # 830049; UPCC #12418