CD22 Redirected Autologous T Cells for ALL

Phase 1

Recruiting

• Conditions: B Cell Leukemias; B Cell Lymphomas
• Interventions: Biological: Cohort 1; Biological: Cohorts 2; Biological: Cohort 3

• Registration Number: NCT02650414
• Lead Sponsor: University of Pennsylvania

Brief Summary

This is a pilot study to determine the feasibility and safety of a single dose of autologous T cells expressing CD22 chimeric antigen receptors expressing tandem TCR-ζ and 4-1BB signaling domains (CART22/CART22-65s cells) in pediatric and young adult subjects with relapsed or refractory B cell acute lymphoblastic leukemia.

Detailed Description

This is a single center, single arm, dual-cohort, open-label pilot study to determine the feasibility and safety of a single dose (administered as split fractions) of autologous T cells expressing CD22 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-

1BB) co-stimulatory domains (referred to as "CART22" and "CART22-65s" cells) in pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Cohort assignment will be dependent on the date of consent and confirmation of eligibility by a physician-investigator as follows:

* Cohort 1: was closed to additional recruitment as of Protocol Version 8. All subjects who received CART22 cells will be retrospectively assigned to Cohort 1.

* Cohort 2: was opened as of Protocol Version 8. All subjects assigned to Cohort 2 will receive CART22-65s cells given over 3 days.

* Cohort 3: will open as of Protocol V12, with subjects enrolled sequentially after all infusion slots in Cohort 2 are filled. All subjects assigned to Cohort 3 will also receive CART22-65s cells, however the product will be administered over 2 days.

Study Timeline

• Study First Submitted: 2015-12-22
• Study First Submitted QC: 2016-01-07
• Study First Posted: 2016-01-08
• Study Start: 2016-01-13
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-16
• Primary Completion: 2037-12
• Study Completion: 2037-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

Not provided

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Exclusion Criteria

1. Active hepatitis B or active hepatitis C.
2. HIV Infection.
3. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
4. Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary.
5. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
6. Pregnant or nursing (lactating) women.
7. Receipt of a prior investigational study agent within 4 weeks prior to screening visit. *Note - patients who have received anti-CD19 CART cells (e.g., CART19/CTL019) on an investigational study where cell infusion occurred greater than 4 weeks before the screening visit are NOT excluded.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia	Cohort 1	-
Pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia	Cohorts 2	-
Pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia	Cohort 3	-

Primary Outcome Measures

Name	Time	Method
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS)	From date of dosing ( day 1 ) up 15 years	grade 3 and higher toxicity rate (toxicity possibly attributed to CART22)

Secondary Outcome Measures

Name	Time	Method
Number of subjects with relapse free survival (RFS)	15 years
Number of subjects with event free survival (EFS).	15 years
Duration of remission (DOR)	15 Years
Percentage of manufacturing products that do not meet release criteria.	3 months	Product must pass for vector transduction efficiency, T cell product purity, viability, sterility or due to tumor contamination.
Overall Complete Remission Rate (ORR) at Day 28.	4 months	Includes CR and CR with incomplete blood count recovery (CRi)
Evaluate disease status at Month 6.	9 months
Describe response in terms of minimal residual disease (MRD).	1 year	Percentage of patients who achieve a CR associated with minimal residual disease (MRD) negative bone marrow as determined by high sensitivity flow cytometry.
Incidence of any grade II-IV aGVHD	15 year
Incidence any chronic GVHD.	15 year
Incidence any extensive, limited cGVHD.	15 year
Evaluate overall response rate (CR/CRi by or at Month 6) at Month 6.	9 months
Overall survival (OS)	15 years
Describe cause of death (COD) when appropriate	15 years
Incidence of any acute GVHD	15 year

Trial Locations

Locations (1)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States