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Study to Assess Adverse Events and Change in Disease Activity of Intravenous (IV) Lemzoparlimab With or Without Oral/IV Dexamethasone and in Combination With Oral/IV/Subcutaneous Anti-Myeloma Regimens in Adult Participants With Multiple Myeloma

Phase 1
Terminated
Conditions
Multiple Myeloma
Interventions
Biological: Lemzoparlimab
Biological: Daratumumab
Registration Number
NCT04895410
Lead Sponsor
AbbVie
Brief Summary

Multiple myeloma (MM) accounts for more than 10% of all blood cancers and 1% of all cancers. The purpose of this study is to assess how safe lemzoparlimab is and how lemzoparlimab moves through the body of adult participants with MM when given with or without dexamethasone, and in combination with other anti-myeloma regimens. Adverse events and change in disease activity will be assessed.

Lemzoparlimab is an investigational drug being developed for the treatment of relapsed/refractory (R/R) MM. Study doctors put the participants in groups called treatment arms. Two different dose levels of lemzoparlimab will be explored. Each treatment arm receives a different treatment combination depending on stage of the study and eligibility. This study will include a dose escalation phase to determine the best dose of lemzoparlimab, followed by a dose expansion phase to confirm the dose. Approximately 163 adult participants with R/R MM will be enrolled in the study in approximately 60 sites worldwide.

In the Dose Escalation arms, participants will receive intravenous (IV) lemzoparlimab with or without dexamethasone (oral/IV) in combination with pomalidomide (oral) or carfilzomib (IV) or subcutaneous (SC) daratumumab in 28-day cycles. In the Dose Expansion arms, participants will receive lemzoparlimab (IV) alone or with dexamethasone (oral/IV) in combination with pomalidomide (oral) or carfilzomib (IV) or daratumumab (SC) in 28-day cycles.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests and side effects.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
8
Inclusion Criteria
  • Diagnosis of relapsed/refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen based on the investigator's determination of the International Myeloma Working Group (IMWG) criteria.

    • Relapsed defined as previously treated myeloma that progresses and requires initiation of salvage therapy, but does not meet criteria for refractory myeloma.
    • Refractory defined as disease that is nonresponsive (failure to achieve minimal response or development of progressive disease) while on primary or salvage therapy, or progresses within 60 days of last therapy.
  • Measurable disease per the protocol within 28 days prior to enrollment.

  • Arm A - Lemzoparlimab with or without Dexamethasone

    • For Both Escalation and Expansion Phase, participant must have refractory to 3 prior lines of treatment of anti-myeloma treatments, as outlined in the protocol.
  • Arm B - Lemzoparlimab + Pomalidomide-Dexamethasone

    • For Escalation Phase - Participant must have received at least 3 prior lines of therapy, as outlined in the protocol.
    • For Expansion Phase- Participant must have received at least 2 prior line of therapy, as outlined in the protocol.
  • Arm C - Lemzoparlimab + Carfilzomib-Dexamethasone

    • For Escalation Phase- Participant must have received at least 3 prior lines of therapy as outlined in the protocol.
    • For Expansion Phase- Participant must have received at least 1 prior line of therapy.
  • Arm D - Lemzoparlimab + Daratumumab-Dexamethasone -- For Both Escalation and Expansion Phase - Participant must: --- Have received at least 3 prior lines of therapy, as outlined in the protocol.

Exclusion Criteria
  • Arm B - Lemzoparlimab + Pomalidomide-Dexamethasone

    • For Both Escalation and Expansion Phase participant must have had no prior treatment with pomalidomide.
  • Arm C - Lemzoparlimab + Carfilzomib-Dexamethasone

    • For Both Escalation and Expansion Phase - prior treatment with carfilzomib.
  • Arm D - Lemzoparlimab + Daratumumab-Dexamethasone

    • For Both Escalation and Expansion Phase - prior treatment with daratumumab or other anti-CD38 therapy.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose Escalation: LemzoparlimabLemzoparlimabParticipants will receive lemzoparlimab in 28 day cycles.
Dose Escalation: Lemzoparlimab + Carfilzomib + DexamethasoneLemzoparlimabParticipants will receive lemzoparlimab + carfilzomib + dexamethasone in 28 day cycles.
Dose Escalation: Lemzoparlimab + Daratumumab + DexamethasoneLemzoparlimabParticipants will receive lemzoparlimab + daratumumab + dexamethasone in 28 day cycles.
Dose Escalation: Lemzoparlimab + Daratumumab + DexamethasoneDaratumumabParticipants will receive lemzoparlimab + daratumumab + dexamethasone in 28 day cycles.
Dose Escalation: Lemzoparlimab + Pomalidomide + DexamethasoneLemzoparlimabParticipants will receive lemzoparlimab + pomalidomide + dexamethasone in 28 day cycles.
Dose Expansion: Lemzoparlimab + Pomalidomide + DexamethasoneLemzoparlimabParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion + pomalidomide + dexamethasone in 28 day cycles.
Dose Expansion: Lemzoparlimab + DexamethasoneLemzoparlimabParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion + dexamethasone in 28 day cycles.
Dose Expansion: Lemzoparlimab + Daratamumab + DexamethasoneDaratumumabParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion + daratamumab + dexamethasone in 28 day cycles.
Dose Expansion: LemzoparlimabLemzoparlimabParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion in 28 day cycles.
Dose Expansion: Lemzoparlimab + Carfilzomib + DexamethasoneLemzoparlimabParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion + carfilzomib + dexamethasone in 28 day cycles.
Dose Expansion: Lemzoparlimab + Daratamumab + DexamethasoneLemzoparlimabParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion + daratamumab + dexamethasone in 28 day cycles.
Dose Escalation: Lemzoparlimab + Carfilzomib + DexamethasoneCarfilzomibParticipants will receive lemzoparlimab + carfilzomib + dexamethasone in 28 day cycles.
Dose Escalation: Lemzoparlimab + Pomalidomide + DexamethasoneDexamethasoneParticipants will receive lemzoparlimab + pomalidomide + dexamethasone in 28 day cycles.
Dose Escalation: Lemzoparlimab + Pomalidomide + DexamethasonePomalidomideParticipants will receive lemzoparlimab + pomalidomide + dexamethasone in 28 day cycles.
Dose Escalation: Lemzoparlimab + Carfilzomib + DexamethasoneDexamethasoneParticipants will receive lemzoparlimab + carfilzomib + dexamethasone in 28 day cycles.
Dose Escalation: Lemzoparlimab + Daratumumab + DexamethasoneDexamethasoneParticipants will receive lemzoparlimab + daratumumab + dexamethasone in 28 day cycles.
Dose Expansion: Lemzoparlimab + DexamethasoneDexamethasoneParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion + dexamethasone in 28 day cycles.
Dose Expansion: Lemzoparlimab + Pomalidomide + DexamethasoneDexamethasoneParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion + pomalidomide + dexamethasone in 28 day cycles.
Dose Expansion: Lemzoparlimab + Pomalidomide + DexamethasonePomalidomideParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion + pomalidomide + dexamethasone in 28 day cycles.
Dose Expansion: Lemzoparlimab + Carfilzomib + DexamethasoneDexamethasoneParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion + carfilzomib + dexamethasone in 28 day cycles.
Dose Expansion: Lemzoparlimab + Carfilzomib + DexamethasoneCarfilzomibParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion + carfilzomib + dexamethasone in 28 day cycles.
Dose Expansion: Lemzoparlimab + Daratamumab + DexamethasoneDexamethasoneParticipants will receive lemzoparlimab at recommended dose determined in Dose Escalation portion + daratamumab + dexamethasone in 28 day cycles.
Primary Outcome Measures
NameTimeMethod
Dose Limiting Toxicities (DLTs) of Lemzoparlimab With or Without Dexamethasone and in Combination With Anti-myeloma Regimens in Participants With Relapsed/Refractory (R/R) Multiple Myeloma (MM)Up to 28 days after study drug administration

DLT events as described in the protocol will be assessed.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving Best Overall Response of Documented Partial Response (PR) or BetterUp to approximately 2 years

Best overall response is defined as achieving documented PR or better at two consecutive disease assessments during the study, according to International Myeloma Working Group (IMWG) 2016 criteria.

Progression Free Survival (PFS)Up to approximately 2 years

PFS is defined as the time from the first dose of study drug to the first documented progressive disease (PD) or death due to any cause, whichever occurs first.

Duration of Response (DOR)Up to approximately 2 years

DOR is defined as the time from first documented response (PR or better) to the first documented PD or death due to MM, whichever occurs first.

Time to Progression (TTP)Up to approximately 2 years

TTP is defined as the time from the first dose of study drug to the first documented PD or death due to MM, whichever occurs first.

Trial Locations

Locations (32)

Moffitt Cancer Center /ID# 229939

🇺🇸

Tampa, Florida, United States

Norton Cancer Institute - St Matthews /ID# 229319

🇺🇸

Louisville, Kentucky, United States

University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 229309

🇺🇸

Ann Arbor, Michigan, United States

Rutgers Cancer Institute of New Jersey /ID# 230174

🇺🇸

New Brunswick, New Jersey, United States

Columbia University Medical Center /ID# 229971

🇺🇸

New York, New York, United States

Wake Forest Baptist Health /ID# 229996

🇺🇸

Winston-Salem, North Carolina, United States

Perelman Center for Advanced Medicine - /ID# 228693

🇺🇸

Philadelphia, Pennsylvania, United States

University of Virginia /ID# 229396

🇺🇸

Charlottesville, Virginia, United States

The Queen Elizabeth Hospital /ID# 229345

🇦🇺

Woodville South, South Australia, Australia

Alfred Health /ID# 229347

🇦🇺

Melbourne, Victoria, Australia

HCL - Hôpital Lyon Sud /ID# 229834

🇫🇷

Pierre Benite CEDEX, Auvergne-Rhone-Alpes, France

CHU de Nantes, Hotel Dieu -HME /ID# 228559

🇫🇷

Nantes, Pays-de-la-Loire, France

Hopital Henri Mondor /ID# 228562

🇫🇷

Creteil, France

CHU Poitiers - La milétrie /ID# 229833

🇫🇷

Poitiers, Poitou-Charentes, France

Asklepios Klinik Altona /ID# 229143

🇩🇪

Hamburg, Germany

The Chaim Sheba Medical Center /ID# 229483

🇮🇱

Ramat Gan, Tel-Aviv, Israel

Tel Aviv Sourasky Medical Center /ID# 229478

🇮🇱

Tel Aviv-Yafo, Tel-Aviv, Israel

Rambam Health Care Campus /ID# 229485

🇮🇱

Haifa, Israel

Hadassah Medical Center-Hebrew University /ID# 229477

🇮🇱

Jerusalem, Israel

Meir Medical Center /ID# 229480

🇮🇱

Kfar Saba, Israel

Rabin Medical Center /ID# 229488

🇮🇱

Petakh Tikva, Israel

University Hospital Kyoto Prefectural University of Medicine /ID# 241833

🇯🇵

Kyoto-shi, Kyoto, Japan

Hospital Clínico Universitario de Santiago-CHUS /ID# 229356

🇪🇸

Santiago de Compostela, A Coruna, Spain

Hospital Unversitario Marques de Valdecilla /ID# 229354

🇪🇸

Santander, Cantabria, Spain

Hospital Parc de Salut del Mar /ID# 229371

🇪🇸

Barcelona, Spain

Hospital Santa Creu i Sant Pau /ID# 229369

🇪🇸

Barcelona, Spain

Hospital Universitario Reina Sofia /ID# 229388

🇪🇸

Cordoba, Spain

Hospital Universitario 12 de Octubre /ID# 229355

🇪🇸

Madrid, Spain

Sylvester Comprehensive Cancer Center /ID# 228817

🇺🇸

Miami, Florida, United States

Henry Ford Health System /ID# 230341

🇺🇸

Detroit, Michigan, United States

Duke University Hospital /ID# 229564

🇺🇸

Durham, North Carolina, United States

Tulane Cancer Center Clinic /ID# 229832

🇺🇸

New Orleans, Louisiana, United States

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