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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 : Active, not recruiting
First Posted : November 14, 2014
Last Update Posted : September 7, 2023
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Description
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Brief Summary:
This study has two parts with distinct study objectives and study design. In part A, odronextamab is studied as an intravenous (IV) administration with a dose escalation and a dose expansion phase for B-NHL and CLL. The dose escalation phase for B-NHL and the CLL study are closed at the time of protocol amendment 17. In part B, odronextamab is studied as a subcutaneous (SC) administration with a dose finding and a dose expansion phase for B-NHL.

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

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 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 2, 2025
Estimated Study Completion Date : December 2, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part A
DLBCL post CAR-T
 Drug: Odronextamab multiple dose levels
Administered by intravenous (IV) infusion
Other Name: REGN1979
Experimental: 1N Part B
FL
 Drug: Odronextamab multiple dose levels
Administered by subcutaneous (SC) injection
Other Name: REGN1979
Experimental: 2N Part B
DLBCL
 Drug: Odronextamab multiple dose levels
Administered by subcutaneous (SC) injection
Other Name: REGN1979


Outcome Measures
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Primary Outcome Measures :
  1. Safety/overall frequency of adverse events (AEs) [ Time Frame: Up to 24 months ]
    Part A and B

  2. Safety/dose limiting toxicities (DLTs) [ Time Frame: Up to 28 days ]
    Part A and B

  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

    Part A



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

    Peak plasma concentration (Cmax) of odronextamab

    Part A and B


  2. Incidence of anti-drug antibodies (ADA) to odronextamab [ Time Frame: Over time; up to approximately 15 months ]
    Part A and B

  3. Titer of ADA to odronextamab [ Time Frame: Over time; up to approximately 15 months ]
    Part A and B

  4. Incidence of neutralizing antibodies (NAb) to odronextamab over time [ Time Frame: Over time; Up to approximately 15 months ]
    Part A and B

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

    For dose escalation portion and expansion cohorts:

    • Aggressive lymphoma expansion cohort 2
    • FL grade 1-3a expansion cohorts 1 and 2 (Part A)

    For dose escalation and dose expansion cohorts:

    • FL grade 1-3a
    • DLBCL
    • DLBCL post CAR T failure (Part B)

  6. Progression-free survival [ Time Frame: Up to 48 months ]
    Part A and B

  7. Overall Survival [ Time Frame: Until death or lost to follow-up/ withdrawal, approximately up to 48 months ]
    Part A and B

  8. Duration of response (DOR) [ Time Frame: Until progression, approximately up to 48 months ]
    Part A and B

  9. Minimal residual disease (MRD) for patients with CLL [ Time Frame: Up to 24 months ]
    Part A

  10. Duration of Complete Response (DOCR) [ Time Frame: Until progression, approximately up to 48 months ]
    Part B


Eligibility Criteria
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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

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:

    • Part A (IV administration) B-NHL confirmed by National Cancer Institute (NCI) working group criteria
    • Part B (SC administration): Confirmed diagnosis of B-NHL requiring therapy as defined by WHO classification 2017

  2. Patients with B-NHL must have had prior treatment with an anti-CD20 antibody therapy. Patients with CLL (Part A only) are not required to have received prior treatment with an anti-CD20 antibody therapy as defined in the protocol.

    • 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.
    • For inclusion in Part B, patients must have FL grade 1-3a or DLBCL (with or without prior CAR-T) per the criteria above, and:
    • Patients with FL grade 1-3a and DLBCL must have received at least 2 prior lines of systemic therapy, including an anti-CD20 antibody and an alkylating agent
  3. All patients must have at least one bi-dimensionally measurable lesion ≥1.5 cm) documented by CT or MRI scan, if CT scan is not feasible.
  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  5. Life expectancy of at least 6 months
  6. Adequate bone marrow function as described in the protocol
  7. Adequate organ function as described in the protocol
  8. Willingness to undergo mandatory tumor biopsy pretreatment, if in the opinion of the investigator, the patient has an accessible lesion that can be biopsied without significant risk to the patient.
  9. Willing and able to comply with clinic visits and study-related procedures
  10. Provide signed informed consent or legally acceptable representative

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 such as

    • Epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis, or
    • Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI
  3. Standard anti-lymphoma chemotherapy (non-biologic) or radiotherapy within 28 days prior to first administration of study drug

  4. Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV) infection [(as noted by detectable levels on a blood polymerase chain reaction (PCR) assay)].

    1. Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus deoxyribonucleic acid (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.
    2. Patients who show detectable levels of CMV at screening will need to be treated with appropriate antiviral therapy and demonstrate at least 2 undetectable levels of CMV by PCR assay (at least 7 days apart) before being re-considered for eligibility.
  5. Patients who have received a live vaccination within 28 days of first dose of study treatment

Note: Other protocol Inclusion/Exclusion criteria apply

Contacts and Locations
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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


Locations
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Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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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: September 7, 2023
Last Verified: September 2023

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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
Hematologic Diseases
Leukemia, B-Cell
Chronic Disease
Disease Attributes
Pathologic Processes