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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04155710
Recruitment Status : Recruiting
First Posted : November 7, 2019
Last Update Posted : March 6, 2020
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Biological: IOV-2001 Drug: Low dose IL-2 Drug: High dose IL-2 Drug: IL-2 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 19, 2020
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1a
CLL/SLL patients whose disease has relapsed or is relapsing post ibrutinib therapy. Patients will receive IOV-2001 + low dose IL-2.
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

Experimental: Cohort 1b
CLL/SLL patients whose disease has relapsed or is relapsing post ibrutinib therapy. Patients will receive IOV-2001 + high dose IL-2.
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: 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

Experimental: Cohort 2
CLL/SLL patients with del 17p who progressed or are progressing on ibrutinib therapy. Patients will receive IOV-2001 + IL-2.
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: IL-2
6 doses of IL-2 will follow the infusion of IOV-2001
Other Name: Interleukin-2

Experimental: Cohort 3
CLL/SLL patients without del 17p who progressed or progressing on ibrutinib therapy. Patients will receive IOV-2001 + IL-2.
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: IL-2
6 doses of IL-2 will follow the infusion of IOV-2001
Other Name: Interleukin-2




Primary Outcome Measures :
  1. 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)

  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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04155710


Contacts
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Contact: Iovance Biotherapeutics Clinical Inquiries 866.565.4410 Clinical.Inquiries@iovance.com

Locations
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United States, Ohio
Iovance Investigative Site Recruiting
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Iovance Biotherapeutics, Inc.
Investigators
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Study Chair: Iovance Biotherapeutics Medical Monitor Iovance Biotherapeutics, Inc.

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Responsible Party: Iovance Biotherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04155710    
Other Study ID Numbers: IOV-CLL-01
First Posted: November 7, 2019    Key Record Dates
Last Update Posted: March 6, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Iovance Biotherapeutics, Inc.:
Autologous Peripheral Blood Lymphocytes
PBL
IOV-2001
CLL
IL-2
Adoptive Cell Therapy
SLL
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Interleukin-2
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs