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CART22 Alone or in Combination With huCART19 for ALL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03620058
Recruitment Status : Active, not recruiting
First Posted : August 8, 2018
Last Update Posted : February 24, 2023
Information provided by (Responsible Party):
University of Pennsylvania

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
Chemotherapy Resistant Acute Lymphoblastic Leukemia Refractory Acute Lymphoblastic Leukemia Biological: CART22-65s cells Biological: huCART19 Cells Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 27, 2018
Estimated Primary Completion Date : January 2036
Estimated Study Completion Date : January 2036

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

Primary Outcome Measures :
  1. 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).

  2. 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).

Secondary Outcome Measures :
  1. 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).

  2. Tumor response. [ Time Frame: 6 months ]
    overall response rate (CR/CRi by or at Month 6) and disease response status at Month 6

  3. Tumor response. [ Time Frame: 1 Year ]
    overall survival (OS)

  4. Tumor response. [ Time Frame: 1 Year ]
    duration of remission (DOR)

  5. Tumor response. [ Time Frame: 1 Year ]
    relapse free survival (RFS)

  6. Tumor response. [ Time Frame: 1 Year ]
    event free survival (EFS)

  7. CAR T cell kinetics [ Time Frame: 1 Year ]
    Engraftment and persistence in blood by qPCR (or flow cytometry)

  8. 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).

  9. Evaluate bioactivity of CAR T cells [ Time Frame: 1 Year ]
    Measure levels of systemic soluble immune and inflammatory factors by Luminex-based analyses

  10. 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03620058

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United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
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Principal Investigator: Noelle Frey, MD University of Pennsylvania
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Responsible Party: University of Pennsylvania Identifier: NCT03620058    
Other Study ID Numbers: IRB # 830049; UPCC #12418
First Posted: August 8, 2018    Key Record Dates
Last Update Posted: February 24, 2023
Last Verified: February 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases