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

NCT ID: NCT04155710

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-19

Study Completion Date

2024-12-02

Brief Summary

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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

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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.

Conditions

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Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

IOV-2001

Intervention Type BIOLOGICAL

Adoptive cell therapy (ACT) manufactured from peripheral blood lymphocytes (PBL). The final investigational product is a cryopreserved cell suspension.

Low dose IL-2

Intervention Type DRUG

6 doses of subcutaneous (SC) LD-IL-2 (9 MIU every 8-12 hours) will follow the infusion of IOV-2001

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.

Group Type EXPERIMENTAL

IOV-2001

Intervention Type BIOLOGICAL

Adoptive cell therapy (ACT) manufactured from peripheral blood lymphocytes (PBL). The final investigational product is a cryopreserved cell suspension.

High dose IL-2

Intervention Type DRUG

6 doses of IV HD-IL-2 (600,000 IU/kg Q8-12H will follow the infusion of IOV-2001

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.

Group Type EXPERIMENTAL

IOV-2001

Intervention Type BIOLOGICAL

Adoptive cell therapy (ACT) manufactured from peripheral blood lymphocytes (PBL). The final investigational product is a cryopreserved cell suspension.

IL-2

Intervention Type DRUG

6 doses of IL-2 will follow the infusion of IOV-2001

Cohort 3

CLL/SLL patients without del 17p who progressed or progressing on ibrutinib or acalabrutinib therapy. Patients will receive IOV-2001 + IL-2.

Group Type EXPERIMENTAL

IOV-2001

Intervention Type BIOLOGICAL

Adoptive cell therapy (ACT) manufactured from peripheral blood lymphocytes (PBL). The final investigational product is a cryopreserved cell suspension.

IL-2

Intervention Type DRUG

6 doses of IL-2 will follow the infusion of IOV-2001

Interventions

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IOV-2001

Adoptive cell therapy (ACT) manufactured from peripheral blood lymphocytes (PBL). The final investigational product is a cryopreserved cell suspension.

Intervention Type BIOLOGICAL

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

Intervention Type 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

Intervention Type DRUG

IL-2

6 doses of IL-2 will follow the infusion of IOV-2001

Intervention Type DRUG

Other Intervention Names

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Autologous PBL Interleukin-2 Interleukin-2 Interleukin-2

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Iovance Biotherapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Iovance Biotherapeutics Medical Monitor

Role: STUDY_CHAIR

Iovance Biotherapeutics, Inc.

Locations

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Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Allegheny Health

Pittsburgh, Pennsylvania, United States

Site Status

Baptist Cancer Center

Memphis, Tennessee, United States

Site Status

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Countries

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United States

Other Identifiers

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IOV-CLL-01

Identifier Type: -

Identifier Source: org_study_id