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

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ClinicalTrials.gov Identifier: NCT04155710
Recruitment Status : Recruiting
First Posted : November 7, 2019
Last Update Posted : January 19, 2021
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE November 4, 2019
First Posted Date  ICMJE November 7, 2019
Last Update Posted Date January 19, 2021
Actual Study Start Date  ICMJE February 19, 2020
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2021)
  • Phase I: RP2D (Recommended Phase 2 Dose) [ Time Frame: up to one year or depending on when the recommended phase 2 dose is determined ]
    to determine the recommended Phase 2 dose of IOV-2001 followed by interleukin-2 (IL-2)
  • Phase 2: Objective Response Rate [ Time Frame: up to two years ]
    To evaluate efficacy of the RP2D of IOV-2001 followed by IL-2 as measured by objective response rate (ORR) per investigator assessment
Original Primary Outcome Measures  ICMJE
 (submitted: November 5, 2019)
  • Phase I: RP2D (Recommended Phase 2 Dose) [ Time Frame: up to one year or depending on when the recommended phase 2 dose is determined ]
    to determine the recommended Phase 2 dose of IOV-2001 followed by interleukin-2 (IL-2)
  • Phase 2: Objective Response Rate [ Time Frame: up to two years ]
    To evaluate efficacy of the RP2D of IOV-2001 as measured by objective response rate (ORR) per investigator assessment
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2019)
  • Phase 1: Adverse Events [ Time Frame: up to one year or depending on when the recommended phase 2 dose is determined ]
    Incidence of adverse events (AEs) and serious AEs
  • Phase 1: Disease Assessment [ Time Frame: up to two years ]
    To assess the evidence of activity of IOV-2001 followed by IL-2 as measured by ORR per Investigator assessment
  • Phase 1: Disease Assessment [ Time Frame: up to two years ]
    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
  • Phase 1: Disease Assessment [ Time Frame: up to two years ]
    To assess minimum residual disease (MRD)-negative rate for IOV-2001 followed by IL-2
  • Phase 2: Disease Assessment (Separately for each cohort) [ Time Frame: up to two years ]
    To assess progression free survival (PFS) of IOV-2001 therapy followed by IL-2
  • Phase 2: Disease Assessment (Separately for each cohort) [ Time Frame: up to two years ]
    To assess overall survival (OS) of IOV-2001 therapy followed by IL-2
  • Phase 2: Disease Assessment (Separately for each cohort) [ Time Frame: up to two years ]
    To assess duration of response (DOR) of IOV-2001 therapy followed by IL-2
  • Phase 2: Disease Assessment (Separately for each cohort) [ Time Frame: up to two years ]
    To assess disease control rate (DCR) of IOV-2001 therapy followed by IL-2
Original Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2019)
  • Phase 1: Adverse Events [ Time Frame: up to one year or depending on when the recommended phase 2 dose is determined ]
    Incidence of adverse events (AEs) and serious AEs
  • Phase 1: Disease Assessment [ Time Frame: up to two years ]
    To assess the evidence of activity of IOV-2001 followed by IL-2 as measured by ORR per Investigator assessment
  • Phase 1: Disease Assessment [ Time Frame: up to two years ]
    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
  • Phase 1: Disease Assessment [ Time Frame: up to two years ]
    To assess minimum residual disease (MRD)-negative rate for IOV-2001 followed by IL-2
  • Phase 2: Disease Assessment (Separately for each cohort) [ Time Frame: up to two years ]
    To assess PFS of IOV-2001 therapy followed by IL-2
  • Phase 2: Disease Assessment (Separately for each cohort) [ Time Frame: up to two years ]
    To assess OS of IOV-2001 therapy followed by IL-2
  • Phase 2: Disease Assessment (Separately for each cohort) [ Time Frame: up to two years ]
    To assess DOR of IOV-2001 therapy followed by IL-2
  • Phase 2: Disease Assessment (Separately for each cohort) [ Time Frame: up to two years ]
    To assess DCR of IOV-2001 therapy followed by IL-2
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Autologous Peripheral Blood Lymphocytes in the Treatment of Patients With CLL or SLL
Official Title  ICMJE 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
Brief Summary This is a Phase 1/2, study evaluating IOV-2001 (Adoptive Cell Therapy) composed of autologous PBL (Peripheral Blood Lymphocytes) in patients with CLL/SLL, which has relapsed or is relapsing during treatment with ibrutinib or acalabrutinib.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
Intervention  ICMJE
  • Biological: IOV-2001
    Adoptive cell therapy (ACT) manufactured from peripheral blood lymphocytes (PBL). The final investigational product is a cryopreserved cell suspension.
    Other Name: Autologous PBL
  • Drug: Low dose IL-2
    6 doses of subcutaneous (SC) LD-IL-2 (9 MIU every 8-12 hours) will follow the infusion of IOV-2001
    Other Name: Interleukin-2
  • Drug: High dose IL-2
    6 doses of IV HD-IL-2 (600,000 IU/kg Q8-12H will follow the infusion of IOV-2001
    Other Name: Interleukin-2
  • Drug: IL-2
    6 doses of IL-2 will follow the infusion of IOV-2001
    Other Name: Interleukin-2
Study Arms  ICMJE
  • Experimental: Cohort 1a
    CLL/SLL patients whose disease has relapsed or is relapsing post ibrutinib or acalabrutinib therapy. Patients will receive IOV-2001 + low dose IL-2.
    Interventions:
    • Biological: IOV-2001
    • Drug: Low dose IL-2
  • Experimental: Cohort 1b
    CLL/SLL patients whose disease has relapsed or is relapsing post ibrutinib or acalabrutinib therapy. Patients will receive IOV-2001 + high dose IL-2.
    Interventions:
    • Biological: IOV-2001
    • Drug: High dose IL-2
  • Experimental: Cohort 2
    CLL/SLL patients with del 17p who progressed or are progressing on ibrutinib or acalabrutinib therapy. Patients will receive IOV-2001 + IL-2.
    Interventions:
    • Biological: IOV-2001
    • Drug: IL-2
  • Experimental: Cohort 3
    CLL/SLL patients without del 17p who progressed or progressing on ibrutinib or acalabrutinib therapy. Patients will receive IOV-2001 + IL-2.
    Interventions:
    • Biological: IOV-2001
    • Drug: IL-2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 5, 2019)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2023
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients with CLL or SLL with radiographically measurable disease

    • Cohort 2 only: patients with progressed or progressing CLL/SLL on ibrutinib or acalabrutinib with del 17p and/or TP53 mutated
    • Cohort 3 only: patients with progressed or progressing CLL/SLL on ibrutinib or acalabrutinib without del 17p and/or TP53 mutated
  2. Patients must have documented progression or be progressing on ibrutinib or acalabrutinib, as indicated by the presence of known BTK resistance mutation
  3. Patients must have received at least 1 prior regimen (only for patients without del 17p and/or TP53 mutated) and currently be on ibrutinib or acalabrutinib. For patients on combination therapy as the last line of therapy prior study entry, progression to any of the individual components of the combination therapy, rather than to the combination regimen, is required.

    • For Cohort 2: The single prior regimen can be ibrutinib or acalabrutinib (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 or acalabrutinib
  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 or acalabrutinib
  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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Iovance Biotherapeutics Clinical Inquiries 866.565.4410 Clinical.Inquiries@iovance.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04155710
Other Study ID Numbers  ICMJE IOV-CLL-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Iovance Biotherapeutics, Inc.
Study Sponsor  ICMJE Iovance Biotherapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Iovance Biotherapeutics Medical Monitor Iovance Biotherapeutics, Inc.
PRS Account Iovance Biotherapeutics, Inc.
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP