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Study to Investigate the Safety and Tolerability of Odronextamab in Patients With CD20+ B-Cell Malignancies (ELM-1)

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ClinicalTrials.gov Identifier: NCT02290951
Recruitment Status : Recruiting
First Posted : November 14, 2014
Last Update Posted : July 1, 2021
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

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

Condition or disease Intervention/treatment Phase
Non-Hodgkin Lymphoma Chronic Lymphocytic Leukemia Drug: Odronextamab multiple dose levels Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 256 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 (ELM-1)
Actual Study Start Date : January 9, 2015
Estimated Primary Completion Date : December 5, 2025
Estimated Study Completion Date : December 5, 2025


Arm Intervention/treatment
Experimental: Experimental cohorts N
Experimental cohorts N (participants with CD20+NHL) will receive multiple dose levels of odronextamab
Drug: Odronextamab multiple dose levels
Administered by intravenous (IV) infusion
Other Name: REGN1979

Experimental: Experimental cohorts C
Experimental cohorts C (participants with CLL) will receive multiple dose levels of odronextamab
Drug: Odronextamab multiple dose levels
Administered by intravenous (IV) infusion
Other Name: REGN1979




Primary Outcome Measures :
  1. Safety/overall frequency of adverse events [ Time Frame: Up to 24 months ]
  2. Safety/dose limiting toxicities (DLTs) [ Time Frame: Up to 28 days ]
  3. Antitumor activity as measured by the objective response rate (ORR) [ Time Frame: Through study completion, an average of 24 months ]

    Expansion Cohorts:

    • Diffuse large B-cell lymphoma (DLBCL) after failure of CAR-T therapy



Secondary Outcome Measures :
  1. Pharmacokinetics (Concentration of odronextamab) [ Time Frame: Up to 10 months ]
    Peak plasma concentration (Cmax) of odronextamab

  2. Immunogenicity (Anti-odronextamab antibodies) [ Time Frame: Up to 15 months ]
    Anti-odronextamab antibodies

  3. Objective response rate (ORR) [ Time Frame: Through study completion, an average of 24 months ]

    For dose escalation portion

    Expansion cohorts:

    • Aggressive lymphoma expansion cohort 2
    • FL grade 1-3a expansion cohorts 1 and 2

  4. Progression-free survival [ Time Frame: Up to 48 months ]
  5. Overall Survival [ Time Frame: Until death or lost to follow-up/ withdrawal, approximately up to 48 months ]
  6. Duration of response (DOR) [ Time Frame: Until progression, approximately up to 48 months ]
  7. Minimal residual disease (MRD) for patients with CLL [ Time Frame: Up to 24 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Enrollment is closed for CLL, FL grade 1-3a and aggressive lymphoma cohorts. The only cohort that remains open for enrollment is the DLBCL after failure of CAR-T therapy cohort.

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 on the longest diameter 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.


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): NCT02290951


Contacts
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Contact: Clinical Trials Administrator clinicaltrials@regeneron.com

Locations
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United States, California
University of California, Irvine Recruiting
Orange, California, United States, 92868
Stanford University Recruiting
Stanford, California, United States, 94305
United States, Florida
Moffitt Cancer Center Completed
Tampa, Florida, United States, 33612
United States, Massachusetts
Dana Farber Cancer Institute (Massachusetts General Hospital and Beth Israel) Recruiting
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08901
United States, New York
Memorial Sloan Kettering Cancer Center Completed
New York, New York, United States, 10065
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Germany
Universitatsklinikum Wurzburg Recruiting
Wurzburg, Germany
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02290951    
Other Study ID Numbers: R1979-HM-1333
2015-004491-30 ( EudraCT Number )
First Posted: November 14, 2014    Key Record Dates
Last Update Posted: July 1, 2021
Last Verified: June 2021

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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 Regeneron Pharmaceuticals:
Diffuse large B-cell lymphoma (DLBCL)
Follicular lymphoma (FL)
Aggressive lymphoma
Additional relevant MeSH terms:
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Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Leukemia
Leukemia, B-Cell