CART22 Alone or in Combination With huCART19 for ALL

Refractory Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03620058
• Other study ID #: IRB # 830049; UPCC #12418
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 27, 2018
• Est. completion date: January 2036

Study information

• Verified date: February 2023
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 23
• Est. completion date: January 2036
• Est. primary completion date: January 2036
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. CNS1 - no blasts seen on cytocentrifuge (CNS negative);

2. CNS2 - total nucleated cell count <5x106/L, but blasts seen on cytocentrifuge;

3. 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:

1. Creatinine = 1.6 mg/dl

2. ALT/AST = 3x upper limit of normal range

3. Total or Direct bilirubin = 2.0 mg/dl. If Total bilirubin is =2.0, Direct bilirubin does not need to be assessed.

4. 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.

Related Conditions & MeSH terms

• Chemotherapy Resistant Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Refractory Acute Lymphoblastic Leukemia

Intervention

Biological:
• CART22-65s cells
Autologous T cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB
• huCART19 Cells
Autologous T cells transduced with lentiviral vector to express anti-CD19 scFv TCR?:4-1BB

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the safety of CART22-65s in ALL subjects using the common terminology criteria of adverse events (CTCAE) v5.0.	Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).	15 months
Primary	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.	Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).	15 months
Secondary	Tumor response.	Overall Complete Remission Rate (ORR) at Day 28 which includes CR and CR with incomplete blood count recovery (CRi).	28 Days
Secondary	Tumor response.	overall response rate (CR/CRi by or at Month 6) and disease response status at Month 6	6 months
Secondary	Tumor response.	overall survival (OS)	1 Year
Secondary	Tumor response.	duration of remission (DOR)	1 Year
Secondary	Tumor response.	relapse free survival (RFS)	1 Year
Secondary	Tumor response.	event free survival (EFS)	1 Year
Secondary	CAR T cell kinetics	Engraftment and persistence in blood by qPCR (or flow cytometry)	1 Year
Secondary	CAR T cell kinetics	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
Secondary	Evaluate bioactivity of CAR T cells	Measure levels of systemic soluble immune and inflammatory factors by Luminex-based analyses	1 Year
Secondary	Determine antigen expression and normal B cell levels in response to CAR T cells	Measure CD22, CD19 and B cell levels pre- and post-CAR T cell infusion by flow cytometry	1 Year