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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:

Active, not recruiting

Phase:

N/A

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+ Chronic Lymphocytic Leukemia (CLL)Or Small Lymphocytic Lymphoma (SLL)

Clinical Trial IDs

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

Conditions

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

Interventions

DrugSynonymsArms

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.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Arm 1Experimental

    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:

    Secondary Outcome Measures

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University of Pennsylvania

    Trial Keywords

      Last Updated

      September 27, 2016