Clinical Trials /

CART22 Alone or in Combination With huCART19 for ALL

NCT03620058

Description:

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.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CART22 Alone or in Combination With huCART19 for ALL
  • 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 IDs

  • ORG STUDY ID: IRB # 830049; UPCC #12418
  • NCT ID: NCT03620058

Conditions

  • Chemotherapy Resistant Acute Lymphoblastic Leukemia
  • Refractory Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
CART22-65s cellsCART22-65s monotherapy
huCART19 CellsCART22-65s in combination with huCART19

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
CART22-65s monotherapyExperimental
    CART22-65s in combination with huCART19Experimental

      Eligibility Criteria

              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 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.
      
                -  9. Receipt of a prior investigational study agent within 4 weeks prior to eligibility
                   confirmation by investigator.
      
                -  10. Patients with a known history or prior diagnosis of optic neuritis or other
                   immunologic or inflammatory disease affecting the central nervous system.
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Assess the safety of CART22-65s in ALL subjects using the common terminology criteria of adverse events (CTCAE) v5.0.
      Time Frame:15 months
      Safety Issue:
      Description:Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).

      Secondary Outcome Measures

      Measure:Tumor response.
      Time Frame:28 Days
      Safety Issue:
      Description:Overall Complete Remission Rate (ORR) at Day 28 and duration of remission
      Measure:CAR T cell kinetics
      Time Frame:1 Year
      Safety Issue:
      Description:Engraftment and persistence in blood by qPCR (or flow cytometry)
      Measure:Evaluate bioactivity of CAR T cells
      Time Frame:15 months
      Safety Issue:
      Description:Measure levels of systemic soluble immune and inflammatory factors by Luminex-based analyses
      Measure:Determine antigen expression and normal B cell levels in response to CAR T cells
      Time Frame:15 months
      Safety Issue:
      Description:Measure CD22, CD19 and B cell levels pre- and post-CAR T cell infusion by flow cytometry

      Details

      Phase:Phase 1
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:University of Pennsylvania

      Last Updated