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

Sponsor

Iovance Biotherapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04155710

Collaborator

(none)

Enrollment

Locations

Arms

34.4

Anticipated Duration (Months)

11.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

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.

Study Design

Study Type:

Interventional

Anticipated 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 :

Feb 19, 2020

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
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.	Biological: IOV-2001 Adoptive cell therapy (ACT) manufactured from peripheral blood lymphocytes (PBL). The final investigational product is a cryopreserved cell suspension. Other Names: 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 Names: Interleukin-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.	Biological: IOV-2001 Adoptive cell therapy (ACT) manufactured from peripheral blood lymphocytes (PBL). The final investigational product is a cryopreserved cell suspension. Other Names: 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 Names: Interleukin-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.	Biological: IOV-2001 Adoptive cell therapy (ACT) manufactured from peripheral blood lymphocytes (PBL). The final investigational product is a cryopreserved cell suspension. Other Names: Autologous PBL Drug: IL-2 6 doses of IL-2 will follow the infusion of IOV-2001 Other Names: Interleukin-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.	Biological: IOV-2001 Adoptive cell therapy (ACT) manufactured from peripheral blood lymphocytes (PBL). The final investigational product is a cryopreserved cell suspension. Other Names: Autologous PBL Drug: IL-2 6 doses of IL-2 will follow the infusion of IOV-2001 Other Names: Interleukin-2

Outcome Measures

Primary Outcome Measures

Phase I: RP2D (Recommended Phase 2 Dose) [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 [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

Secondary Outcome Measures

Phase 1: Adverse Events [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 [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 [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 [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) [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) [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) [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) [up to two years]
To assess disease control rate (DCR) of IOV-2001 therapy followed by IL-2

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Patients must have documented progression or be progressing on ibrutinib or acalabrutinib, as indicated by the presence of known BTK resistance mutation
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

Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of ≥ 3 months.
Patients must have adequate bone marrow function to receive NMA-LD
Pulmonary function assessed by spirometry demonstrating FEV1 > 50% predicted normal
Cardiac function demonstrating left ventricular ejection fraction (LVEF) > 45%
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:

Patients who have received an organ allograft or prior cell transfer therapy within 20 years.
Patients with known or suspected transformed disease (ie, Richter's Transformation).
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
Patients with known involvement of central nervous system (CNS) by lymphoma or leukemia
Patients who are on chronic systemic steroid therapy >5 mg/day prednisone equivalent for any reason
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.
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)

Patients with active and chronic fungal, bacterial, or viral infection requiring IV treatment
Patients who require treatment for anti-coagulation with a vitamin K antagonist (warfarin)
Patients who have received a live or attenuated vaccine within 28 days of beginning the preparative NMA-LD regimen
Patients who are pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Moffitt Cancer Center	Tampa	Florida	United States	33612
2	Duke University	Durham	North Carolina	United States	27710
3	Ohio State University	Columbus	Ohio	United States	43210
4	Allegheny Health	Pittsburgh	Pennsylvania	United States	15224
5	Baptist Cancer Center	Memphis	Tennessee	United States	38120
6	University of Utah, Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112