Clinical Trials /

Study to Investigate the Safety and Tolerability of REGN1979 in Patients With CD20+ B-Cell Malignancies

NCT02290951

Description:

This is an open-label, multi-center, dose escalation study of REGN1979 administered as an IV (intravenous) infusion. This phase 1 study will investigate the safety and tolerability of REGN1979 in patients with B-cell Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Grade 1 Follicular Lymphoma
  • Grade 2 Follicular Lymphoma
  • Grade 3 Follicular Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study to Investigate the Safety and Tolerability of REGN1979 in Patients With CD20+ B-Cell Malignancies
  • Official Title: An Open-Label, Multi-Center Phase 1 Study to Investigate the Safety and Tolerability of REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, in Patients With CD20+ B-Cell Malignancies Previously Treated With CD20-Directed Antibody Therapy

Clinical Trial IDs

  • ORG STUDY ID: R1979-HM-1333
  • SECONDARY ID: 2015-004491-30
  • NCT ID: NCT02290951

Conditions

  • Non-Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia

Interventions

DrugSynonymsArms
REGN1979 multiple dose levelsExperimental cohorts C
RituximabExperimental cohorts N

Purpose

This is an open-label, multi-center, dose escalation study of REGN1979 administered as an IV (intravenous) infusion. This phase 1 study will investigate the safety and tolerability of REGN1979 in patients with B-cell Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

Trial Arms

NameTypeDescriptionInterventions
Experimental cohorts NExperimentalExperimental cohorts N (participants with CD20+NHL) will receive multiple dose levels of REGN1979 Rituximab lead-in cohort N will receive multiple dose regimens of REGN1979
  • REGN1979 multiple dose levels
  • Rituximab
Experimental cohorts CExperimentalExperimental cohorts C (participants with CLL) will receive multiple dose levels of REGN1979
  • REGN1979 multiple dose levels

Eligibility Criteria

        Key Inclusion Criteria:

          1. Have documented CD20+ B-cell malignancy, with active disease not responsive to prior
             therapy, for whom no standard of care options exists, and for whom treatment with an
             anti-CD20 antibody may be appropriate.

          2. Patients with NHL must have had prior treatment with an anti-CD20 antibody therapy.
             Patients with CLL are not required to have received prior treatment with an anti-CD20
             antibody therapy, provided the patient has failed either a BTK inhibitor or PI3K
             inhibitor and the treating physician deems it appropriate for the patient to be
             entered into a phase 1 trial.

               -  For inclusion in the FL grade 1-3a expansion cohort, patients must have received
                  at least 2 prior lines of systemic therapy, including an anti-CD20 antibody and
                  an alkylating agent.

               -  For the inclusion in the disease-specific expansion cohort enrolling DLBCL
                  patients after failure of CAR-T therapy, the patient must have recovered from the
                  toxicities of the lymphodepletion therapy and CAR-T infusion.

          3. Must have at least one bi-dimensionally measurable lesion ≥1.5 cm) documented by CT or
             MRI scan.

          4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

          5. Life expectancy of at least 6 months

          6. Adequate bone marrow function documented by:

               1. Platelet counts ≥75 x 10^9/L

               2. Hb level ≥9 g/dL

               3. Absolute neutrophil count (ANC) ≥1 x 10^9/L

          7. Adequate organ function documented by:

               1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 X ULN

               2. Total bilirubin ≤1.5 X ULN

               3. Calculated creatinine clearance by Cockcroft-Gault ≥50 mL/min (patients with
                  borderline creatinine clearance by Cockcroft-Gault may be considered for
                  enrollment if a measured creatinine clearance (based on 24-hour urine or other
                  reliable method) is ≥50 mL/min)

          8. Willing and able to comply with clinic visits and study-related procedures

          9. Provide signed informed consent

        Key Exclusion Criteria:

          1. Primary central nervous system (CNS) lymphoma or known or suspected CNS involvement by
             non-primary CNS NHL

          2. History of or current relevant CNS pathology

          3. Allogeneic stem cell transplantation

          4. Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis
             B virus (HBV) or hepatitis C virus (HCV). Patients with hepatitis B (HepBsAg+) who
             have controlled infection (serum hepatitis B virus DNA that is below the limit of
             detection AND receiving anti-viral therapy for hepatitis B) are permitted upon
             consultation with the physician managing the infection.

          5. Known hypersensitivity to both allopurinol and rasburicase

          6. History of hypersensitivity to any compound in the tetracycline antibiotics group

        The information provided above is not intended to contain all considerations relevant to
        potential participation in a clinical trial therefore not all inclusion/ exclusion criteria
        are listed.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety/overall frequency of adverse events
Time Frame:Up to 24 months
Safety Issue:
Description:Expansion Cohorts: Diffuse large B-cell lymphoma (DLBCL) after failure of CAR-T therapy Aggressive lymphoma cohorts 1 and 2 Follicular lymphoma (FL) grade 1-3a cohorts 1 and 2 Rituximab lead-in Chronic lymphocytic leukemia (CLL)

Secondary Outcome Measures

Measure:Pharmacokinetics (Concentration of REGN1979)
Time Frame:Up to 10 months
Safety Issue:
Description:Peak plasma concentration (Cmax) of REGN1979
Measure:Immunogenicity (Anti-REGN1979 antibodies)
Time Frame:Up to 15 months
Safety Issue:
Description:Anti-REGN1979 antibodies
Measure:Objective response rate (ORR)
Time Frame:Through study completion, an average of 24 months
Safety Issue:
Description:For dose escalation portion and rituximab lead-in dose groups
Measure:Progression-free survival
Time Frame:Up to 48 months
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:Up to 48 months
Safety Issue:
Description:
Measure:Minimal residual disease (MRD) for patients with CLL
Time Frame:Up to 24 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Regeneron Pharmaceuticals

Trial Keywords

  • Diffuse large B-cell lymphoma (DLBCL)
  • Follicular lymphoma (FL)
  • Aggressive lymphoma

Last Updated

February 28, 2020