Pilot Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells In Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia

This is a single center, single arm, open-label pilot study to determine the feasibility and safety of a single dose 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" cells) administered in split fractions, in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.

Study Overview

• Status: Terminated
• Conditions: Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Biological: CART22 cells

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of The University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent form must be obtained prior to any research procedure.

2. Relapsed or refractory B-cell ALL:

   a. 1st or greater BM relapse OR b. Any marrow relapse after allogeneic HSCT and > 100 days from transplant OR c. For patients with refractory disease: i. < 60 years old that have not achieved a CR after > 2 or more chemotherapy regimens ii. >60 years old that have not achieved a CR after 1 prior chemotherapy regimen d. Patients with Ph+ ALL are eligible if they are intolerant to or have failed tyrosine kinase inhibitor therapy.

   e. Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy.

3. Documentation of CD22 expression on malignant cells at relapse.

4. Adequate organ function defined as:

   1. Creatinine < 1.6 mg/dl
   2. ALT/AST < 3x upper limit of normal range
   3. Direct bilirubin <2.0 mg/dl
   4. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, pulse oxygen > 92% on room air, and DLCO > 40% (corrected for anemia)
   5. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
5. Evidence of disease by standard morphologic or by MRD criteria.
6. Male or female age ≥ 18 years.
7. ECOG Performance Status that is either 0 or 1.
8. No contraindications for leukapheresis.
9. 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 enrollment.
5. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
6. Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary. 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.
9. Receipt of a prior investigational study agent within 4 weeks prior to enrollment. *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.
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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm	Biological: CART22 cells; CART22 cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB administered by IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Adverse Events	3 years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Noelle Frey, MD, Abramson Cancer Center at Penn Medicine

Publications and helpful links

General Publications

• Singh N, Frey NV, Engels B, Barrett DM, Shestova O, Ravikumar P, Cummins KD, Lee YG, Pajarillo R, Chun I, Shyu A, Highfill SL, Price A, Zhao L, Peng L, Granda B, Ramones M, Lu XM, Christian DA, Perazzelli J, Lacey SF, Roy NH, Burkhardt JK, Colomb F, Damra M, Abdel-Mohsen M, Liu T, Liu D, Standley DM, Young RM, Brogdon JL, Grupp SA, June CH, Maude SL, Gill S, Ruella M. Antigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells. Nat Med. 2021 May;27(5):842-850. doi: 10.1038/s41591-021-01326-5. Epub 2021 Apr 22.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: October 26, 2015
• First Submitted That Met QC Criteria: October 26, 2015
• First Posted (Estimated): October 27, 2015

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: UPCC 31415, 822967