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
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.
Primary Objectives: Phase 1 (Cohorts 1a, 1b): To determine the RP2D of IOV-2001 followed by IL-2 Phase 2 (Cohorts 2 and 3): To evaluate efficacy of the RP2D of IOV-2001 followed by IL-2, as measured by ORR per Investigator assessment Secondary Objectives: Phase 1 (Cohorts 1a, 1b): Secondary objective analysis will be performed separately for patients receiving LD-IL-2 and HD-IL-2: -to evaluate the safety of IOV-2001 followed by IL-2 -to assess the evidence of activity of IOV-2001 followed by IL-2 as measured by ORR per Investigator assessment -to assess progression-free survival (PFS), OS, duration of response (DOR), disease control rate (DCR), complete remission (CR), complete remission with incomplete marrow recovery (CRi), partial remission (PR), and stable disease (SD), of IOV-2001 followed by IL-2 -to assess CR/CRi rate per independent review as defined by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria for IOV-2001 followed by IL-2 -to assess minimum residual disease (MRD)-negative rate for IOV-2001 followed by IL-2 Phase 2 (Cohorts 2 and 3): separately for patients in each cohort: -to assess PFS of IOV-2001 therapy -to assess OS of IOV-2001 therapy -to assess DOR of IOV-2001 therapy -to assess the DCR of IOV-2001 therapy -to assess CR/CRi rate per independent review as defined by iwCLL 2018 criteria of IOV-2001 therapy -to assess MRD-negative rate of IOV-2001 therapy -to further define the safety profile of IOV-2001 therapy Exploratory Objectives (Phases 1 and 2): -to study the in vitro characteristics and the in vivo persistence of IOV-2001, which may affect response, outcome, and toxicity of treatment -to assess the potential immune correlates of the treatment -to explore the properties of the disease that may correlate with IOV-2001 activity
IL-2 (Interleukin-2); IOV-2001 (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)
- 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 acalabutrinib for at least 4 weeks prior to blood sample collection for PBL manufacturing with no current related non-hematologic AE Grade >/=2. Patients who are ventoclax naive must be ineligible and/or deemed inappropriate for treatment with ventoclax (in the opinion of the Investigator the patient is unlikely to receive sufficient benefit) or patients must refuse ventoclax
- 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. 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.
- Patients must be between 18 and 70 years of age at the time of consent. Enrollment of patients over 70 years of age may be allowed after consultation with the Medical Monitor.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of > 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.
- Other criteria may apply
- 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 with an inability to continue taking ibrutinib or acalabrutinib up to 1 day prior to NMA-LD
- 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 virus antigen (HbsAg) or anti-hepatitis B virus core total antibodies (anti-HbcAb), or hepatitis C virus 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
- Other exclusions may apply
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