Clinical Trials /

CD22 Redirected Autologous T Cells for ALL

NCT02650414

Description:

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

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CD22 Redirected Autologous T Cells for ALL
  • Official Title: Pilot Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells in Pediatric Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 15-012219, 823312
  • SECONDARY ID: UPCC 15CT055
  • NCT ID: NCT02650414

Conditions

  • B Cell Leukemias
  • B Cell Lymphomas

Interventions

DrugSynonymsArms
CART22 cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BBCART22 cells

Purpose

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

Detailed Description

      The study will consist of three sequential phases: 1) a screening phase, 2) a manufacturing
      and pre- treatment phase, consisting of apheresis (if applicable) and chemotherapy (if
      applicable), and 3) a treatment phase, consisting of a CART22 transfused cell infusion and
      follow up evaluations.

      After signing informed consent, patients will undergo screening tests and procedures to
      determine eligibility. Once patient eligibility is confirmed, patients will have cells
      collected by leukapheresis to obtain peripheral blood mononuclear cells (PBMC) for CART22
      manufacturing, unless adequate numbers of cells are available from a prior apheresis. Cells
      will be transduced with the anti-CD22 TCRζ/4-1BB lentiviral vector, expanded in vitro and
      then frozen for future administration. Cryopreserved historical apheresis products collected
      from the patient prior to study entry are usable for CART22 manufacturing if collected at an
      appropriately certified apheresis center and the product meets adequate mononuclear cell
      yields. If a historical apheresis product is not available, an apheresis procedure will be
      scheduled for cell procurement after study entry.

      Unless contraindicated and medically not advisable based on previous chemotherapy, patients
      will be given conditioning chemotherapy prior to CART22 cell infusion with the intent of
      lymphodepletion. Additionally, if the patient's white blood cell (WBC) count is ≤ 1,000 /uL,
      conditioning/lymphodepleting chemotherapy is NOT required. The chemotherapy will be planned
      so that the last dose is completed 1-4 days BEFORE the planned infusion of CART22 cells. The
      chemotherapy start date will vary based on the duration of the selected chemotherapy regimen.
      If the period from chemotherapy to CART22 infusion is delayed 4 or more weeks, the patient
      will need to be re-treated with lymphodepleting chemotherapy prior to CART22 infusion.

      We will enroll 15 evaluable patients for the primary safety endpoint analysis. Primary safety
      evaluable patients are those who have received any CART22 cells. The first three subjects
      infused with CART22 will be staggered by 14 days to allow for monitoring of adverse events,
      including CRS.

      Subjects with a manufactured cell dose that is less than the protocol-specified dose will be
      scored as a manufacturing failure. These subjects will receive their cell infusion, provided
      that all other manufacturing release criteria are met.

      All patients will have blood tests to assess CART22 safety, engraftment and persistence at
      regular intervals throughout the study (Visit Evaluation Schedule in Appendix 1). Circulating
      CART22 T cells subsets will be assessed at various times after infusion. CART22 trafficking
      will be assessed in bone marrow aspirates, and other tissues, if available. Follow up is
      planned at a minimum of weekly for 4 weeks, monthly for 6 months, then patients will be
      followed quarterly for the remainder of the year to obtain a medical history, undergo a
      physical examination, and blood tests. Additional samples collections and assessments between
      schedule visits after CART22 cell infusion will be performed as clinically indicated.

      Following these evaluations, patients will enter a roll-over study for long term follow-up
      for up to an additional fourteen years to assess for safety assessments per the FDA
      guidelines.
    

Trial Arms

NameTypeDescriptionInterventions
CART22 cellsExperimentalSubjects <50kg will receive 0.2-1 x 107 CART22 cells/kg as a split dose over three days as follows: Day 1, 10% fraction: 0.2-1x106 CART22 cells/kg Day 2, 30% fraction: 0.6-3x106 CART22 cells/kg Day 3, 60% fraction: 1.2-6x106 CART22 cells/kg Subjects ≥50kg will receive 1-5x108 CART22 cells as a split dose over three days as follows: Day 1, 10% fraction: 1-5x107 Day 2, 30% fraction: 0.3-1.5x108 Day 3, 60% fraction: 0.6-3x108
  • CART22 cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB

Eligibility Criteria

        Inclusion Criteria:

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

          2. Relapsed or refractory B-cell ALL:

               1. 2nd or greater BM relapse OR

               2. Any marrow relapse after allogeneic HSCT and ≥ 6 months from SCT at infusion OR

               3. Any marrow relapse after CAR-modified T cell therapy OR

               4. Refractory disease defined as having not achieved a CR after > 2 chemotherapy
                  regimens OR

               5. Patients with Ph+ ALL are eligible if they are intolerant to or have failed
                  tyrosine kinase inhibitor therapy OR

               6. Ineligible for allogeneic SCT because of:

             i. Comorbid disease ii. Other contraindications to allogeneic SCT conditioning regimen
             iii. Lack of suitable donor iv. Prior SCT v. Declines allogeneic SCT as a therapeutic
             option after documented discussion, with expected outcomes, about the role of SCT with
             a BMT physician not part of the study team g. Patients with CNS3 disease will be
             eligible if CNS disease is responsive to therapy (at infusion, must meet criteria in
             Section 5.2)

          3. Documentation of CD22 tumor expression in bone marrow or peripheral blood by flow
             cytometry at relapse.

          4. Adequate organ function defined as:

               1. A serum creatinine based on age/gender as follows:

                  Maximum Serum Creatinine (mg/dL) Age Male Female

                  1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1.0 1.0 10 to < 13
                  years1.2 1.2 13 to < 16 years1.5 1.4

                  ≥ 16 years 1.7 1.4

               2. ALT/AST < 5x 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; DLCO > 40% (corrected for anemia) if PFTs are
                  clinically appropriate as determined by the treating investigator

               5. Left Ventricle Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 40%
                  confirmed by ECHO/MUGA

          5. Evidence of disease by standard morphologic or by MRD criteria.

          6. Age 1-24 years.

          7. Adequate performance status (Lansky or Karnofsky score ≥50)

          8. Subjects of reproductive potential must agree to use acceptable birth control methods,
             as described in protocol Section 4.3.

        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. For additional details regarding the use of steroids and
             immunosuppressant medication, please see Section 5.6.

          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
             if required by local regulation. *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.
      
Maximum Eligible Age:24 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS)
Time Frame:From date of dosing ( day 1 ) up to 50 weeks
Safety Issue:
Description:grade 3 and higher toxicity rate (toxicity possibly attributed to CART22)

Secondary Outcome Measures

Measure:Evaluate Overall Complete Remission Rate (ORR)
Time Frame:at Day 28
Safety Issue:
Description:
Measure:Evaluate overall response rate including complete remission (CR) and complete remission with incomplete blood count recovery (CRi)
Time Frame:From the date of dosing until death, last follow up, relapse or start of new anticancer therapy, whichever comes first up to 50 weeks
Safety Issue:
Description:
Measure:Evaluate duration of remission (DOR)
Time Frame:at 50 weeks
Safety Issue:
Description:

Details

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

Trial Keywords

  • Biological: CART 22

Last Updated

October 31, 2019