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Pilot Trial Of Autologous T Cells Engineered To Express Anti-CD19 Chimeric Antigen Receptor (CART19)In Combination With Ibrutinib In Patients With Relapsed Or Refractory CD19+ Chronic Lymphocytic Leukemia (CLL)Or Small Lymphocytic Lymphoma (SLL)

NCT02640209

Description:

Open-label pilot study to determine safety and efficacy of CART-19 cells in combination with ibrutinib. The target dose will be 1-5x10xE8 CART-19 transduced cells administered via split dosing: 10% on Day 1, 30% on Day 2, 60% on Day 3. 15 evaluable subjects (adults) with relapsed or refractory CLL/SLL who have achieved partial response or stable disease on ibrutinib therapy will be eligible to receive CART-19 therapy.

Related Conditions:
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Recruiting Status:

Terminated

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Trial Of Autologous T Cells Engineered To Express Anti-CD19 Chimeric Antigen Receptor (CART19)In Combination With Ibrutinib In Patients With Relapsed Or Refractory CD19+ Chronic Lymphocytic Leukemia (CLL)Or Small Lymphocytic Lymphoma (SLL)
  • Official Title: Pilot Trial of Autologous T Cells Engineered to Express Anti-CD19 Chimeric Antigen Receptor (CART19) in Combination With Ibrutinib in Patients With Relapsed or Refractory CD19+ CLL or SLL

Clinical Trial IDs

  • ORG STUDY ID: UPCC 18415, 823584
  • NCT ID: NCT02640209

Conditions

  • LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)

Interventions

DrugSynonymsArms
CART 19Arm 1

Purpose

Open-label pilot study to determine safety and efficacy of CART-19 cells in combination with ibrutinib. The target dose will be 1-5x10xE8 CART-19 transduced cells administered via split dosing: 10% on Day 1, 30% on Day 2, 60% on Day 3. 15 evaluable subjects (adults) with relapsed or refractory CLL/SLL who have achieved partial response or stable disease on ibrutinib therapy will be eligible to receive CART-19 therapy.

Trial Arms

NameTypeDescriptionInterventions
Arm 1Experimental
  • CART 19

Eligibility Criteria

        Inclusion Criteria:

          -  Documented CD19+ CLL or SLL

          -  Successful test expansion -cells (as described in Section 6.1)

          -  Patients must have failed at least 1 prior regimen before Ibrutinib (not including
             single agent rituximab or single agent corticosteroids)

             a. Note: Any relapse after prior autologous SCT will make the patient eligible
             regardless of other prior therapy.

          -  Patients must be currently receiving ibrutinib for at least 6 months prior to
             enrollment in the study and:

               1. Not experiencing any ≥ grade 2 non-hematologic ibrutinib-related toxicity

               2. The best response to ibrutinib therapy must not have exceeded partial response or
                  stable disease (i.e. no CR or CRi)

               3. Note: Patients carrying a deletion at chromosome 17p (i.e. del[17p]), and/or
                  TP53, BTK, and at the PLCγ2 loci mutations, will be eligible if they are
                  receiving frontline therapy with ibrutinib.

          -  ECOG Performance status 0 or 1

          -  18 years of age and older

          -  Adequate organ system function including:

               1. Creatinine < 1.6 mg/dl

               2. ALT/AST < 3x upper limit of normal

               3. Total Bilirubin <2.0 mg/dl with the exception of patients with Gilbert syndrome;
                  patients with Gilbert syndrome may be included if their total bilirubin is ≥ 3.0
                  x ULN and direct bilirubin ≤ 1.5 x ULN.

          -  Patients with relapsed disease after prior allogeneic SCT (myeloablative or
             nonmyeloablative) will be eligible if they meet all other inclusion criteria and:

               1. Have no active GVHD and require no immunosuppression

               2. Are more than 6 months from transplant

          -  No contraindications for leukapheresis

          -  Left Ventricular Ejection fraction >40%

          -  Gives voluntary informed consent

          -  Subjects of reproductive potential must agree to use acceptable birth control methods.

        Exclusion Criteria:

          -  CLL patients with known or suspected transformed disease (i.e. Richter's
             transformation). Note: biopsy proven absence of transformation is not required.

          -  Pregnant or lactating women. The safety of this therapy on unborn children is not
             known. Female study participants of reproductive potential must have a negative serum
             or urine pregnancy test performed within 48 hours before infusion.

          -  Uncontrolled active infection.

          -  Active hepatitis B or hepatitis C infection.

          -  Concurrent use of systemic steroids or chronic use of immunosuppressant medications.
             Recent or current use of inhaled steroids is not exclusionary.

          -  Any uncontrolled active medical disorder that would preclude participation as
             outlined.

          -  HIV infection.

          -  Patients with active CNS involvement with malignancy. Patients with prior CNS disease
             that has been effectively treated will be eligible providing treatment was >4 weeks
             before enrollment.

          -  Class III/IV cardiovascular disability according to the New York Heart Association
             Classification.

          -  Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on
             medical management within two weeks of enrollment.

          -  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:Number of Adverse Events
Time Frame:26 months
Safety Issue:
Description:

Details

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

Last Updated

May 7, 2020