Clinical Trials /

Study of Autologous Peripheral Blood Lymphocytes in the Treatment of Patients With CLL or SLL

NCT04155710

Description:

This is a Phase 1/2, study evaluating IOV-2001 (Adoptive Cell Therapy) composed of autologous PBL (Peripheral Blood Lymphocytes) in patient with CLL/SLL, which has relapsed or is relapsing during treatment with ibrutinib.

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Autologous Peripheral Blood Lymphocytes in the Treatment of Patients With CLL or SLL
  • Official Title: A Phase 1/2 Study Evaluating the Safety and Efficacy of IOV-2001 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: IOV-CLL-01
  • NCT ID: NCT04155710

Conditions

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma

Interventions

DrugSynonymsArms
IOV-2001Autologous PBLCohort 1a
Low dose IL-2Interleukin-2Cohort 1a
High dose IL-2Interleukin-2Cohort 1b
IL-2Interleukin-2Cohort 2

Purpose

This is a Phase 1/2, study evaluating IOV-2001 (Adoptive Cell Therapy) composed of autologous PBL (Peripheral Blood Lymphocytes) in patient with CLL/SLL, which has relapsed or is relapsing during treatment with ibrutinib.

Detailed Description

      This study involves patients receiving nonmyeloablative (NMA) lymphocyte depleting (LD)
      preparative regimen prior to infusion of IOV-2001 followed by IL-2 administration.

      In Phase 1, patients meeting the eligibility criteria will be enrolled and will receive
      treatment with IOV-2001 followed by low dose IL-2 or high dose IL-2.

      After completion of Phase 1, the recommended Phase 2 dose (RP2D) will be evaluated in
      selected patient cohorts defined in the Phase 2 part of the study.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1aExperimentalCLL/SLL patients whose disease has relapsed or is relapsing post ibrutinib therapy. Patients will receive IOV-2001 + low dose IL-2.
  • IOV-2001
  • Low dose IL-2
Cohort 1bExperimentalCLL/SLL patients whose disease has relapsed or is relapsing post ibrutinib therapy. Patients will receive IOV-2001 + high dose IL-2.
  • IOV-2001
  • High dose IL-2
Cohort 2ExperimentalCLL/SLL patients with del 17p who progressed or are progressing on ibrutinib therapy. Patients will receive IOV-2001 + IL-2.
  • IOV-2001
  • IL-2
Cohort 3ExperimentalCLL/SLL patients without del 17p who progressed or progressing on ibrutinib therapy. Patients will receive IOV-2001 + IL-2.
  • IOV-2001
  • IL-2

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with CLL or SLL with indication for treatment per iwCLL 2018 criteria and
             radiographically measurable disease

               -  Cohort 2 only: patients with progressed or progressing CLL/SLL on ibrutinib with
                  del 17p and/or TP53 mutated and/or IgHV unmutated

               -  Cohort 3 only: patients with progressed or progressing CLL/SLL on ibrutinib
                  without del 17p and/or TP53 mutated and/or IgHV unmutated

          2. Patients must have documented progression or be progressing on ibrutinib as indicated
             by the presence of known ibrutinib resistance mutation at ≥ 1% variant allele
             frequency OR < 1% with two separate measurements at least 4 weeks apart with
             increasing variant allele frequency.

          3. Patients must have received at least 1 prior regimen (only for patients without del
             17p and/or TP53 mutated and/or IgHV unmutated) and currently be on ibrutinib.

               -  For Cohort 2: The single prior regimen can be ibrutinib (ie, patients are
                  eligible while progressing on their first line of therapy)

               -  For Cohort 3: Patients must have progressed on at least 1 additional line of
                  therapy in addition to ibrutinib

          4. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0 or 1 and an estimated life expectancy of ≥ 3 months.

          5. Patients must have adequate bone marrow function to receive NMA-LD

          6. Pulmonary function assessed by spirometry demonstrating FEV1 > 50% predicted normal

          7. Cardiac function demonstrating left ventricular ejection fraction (LVEF) > 45%

          8. Patients of childbearing potential or their partners of childbearing potential must be
             willing to practice an approved method of birth control during treatment and for 12
             months after receiving the last protocol-related therapy.

        Exclusion Criteria:

          1. Patients who have received an organ allograft or prior cell transfer therapy within 20
             years.

          2. Patients with known or suspected transformed disease (ie, Richter's Transformation).

          3. Patients who received treatment with any systemic chemotherapy, immunotherapy,
             targeted small molecule inhibitors, or other biologic agents within 30 days or 5
             half-lives, whichever is shorter, of IOV-2001 infusion with the exception of ibrutinib

          4. Patients with known involvement of central nervous system (CNS) by lymphoma or
             leukemia

          5. Patients who are on chronic systemic steroid therapy >5 mg/day prednisone equivalent
             for any reason

          6. Patients who have active systemic infections requiring systemic ABX, autoimmune anemia
             or thrombocytopenia, coagulation disorders, or other active major medical illnesses of
             the cardiovascular, respiratory, or immune system.

          7. Patients who are seropositive for any of the following:

               -  Human immunodeficiency virus (HIV)-1 or HIV-2 antibodies

               -  Hepatitis B antigen (HbsAg) or anti-hepatitis B core total antibodies
                  (anti-HbcAb), or hepatitis C antibody (HCVAb)

          8. Patients with active and chronic fungal, bacterial, or viral infection requiring IV
             treatment

          9. Patients who require treatment for anti-coagulation with a vitamin K antagonist
             (warfarin)

         10. Patients who have received a live or attenuated vaccine within 28 days of beginning
             the preparative NMA-LD regimen

         11. Patients who are pregnant or breastfeeding
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: RP2D (Recommended Phase 2 Dose)
Time Frame:up to one year or depending on when the recommended phase 2 dose is determined
Safety Issue:
Description:to determine the recommended Phase 2 dose of IOV-2001 followed by interleukin-2 (IL-2)

Secondary Outcome Measures

Measure:Phase 1: Adverse Events
Time Frame:up to one year or depending on when the recommended phase 2 dose is determined
Safety Issue:
Description:Incidence of adverse events (AEs) and serious AEs
Measure:Phase 1: Disease Assessment
Time Frame:up to two years
Safety Issue:
Description:To assess the evidence of activity of IOV-2001 followed by IL-2 as measured by ORR per Investigator assessment
Measure:Phase 1: Disease Assessment
Time Frame:up to two years
Safety Issue:
Description:To assess CR/CRi rate per Investigator as defined by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria for IOV-2001 followed by IL-2
Measure:Phase 1: Disease Assessment
Time Frame:up to two years
Safety Issue:
Description:To assess minimum residual disease (MRD)-negative rate for IOV-2001 followed by IL-2
Measure:Phase 2: Disease Assessment (Separately for each cohort)
Time Frame:up to two years
Safety Issue:
Description:To assess progression free survival (PFS) of IOV-2001 therapy followed by IL-2
Measure:Phase 2: Disease Assessment (Separately for each cohort)
Time Frame:up to two years
Safety Issue:
Description:To assess overall survival (OS) of IOV-2001 therapy followed by IL-2
Measure:Phase 2: Disease Assessment (Separately for each cohort)
Time Frame:up to two years
Safety Issue:
Description:To assess duration of response (DOR) of IOV-2001 therapy followed by IL-2
Measure:Phase 2: Disease Assessment (Separately for each cohort)
Time Frame:up to two years
Safety Issue:
Description:To assess disease control rate (DCR) of IOV-2001 therapy followed by IL-2

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Iovance Biotherapeutics, Inc.

Trial Keywords

  • Autologous Peripheral Blood Lymphocytes
  • PBL
  • IOV-2001
  • CLL
  • IL-2
  • Adoptive Cell Therapy
  • SLL

Last Updated

March 5, 2020