Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate Subcutaneous TAK-079 Added to Standard of Care Regimens in Participants With Newly Diagnosed Multiple Myeloma (NDMM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03984097
Recruitment Status : Active, not recruiting
First Posted : June 12, 2019
Last Update Posted : August 5, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The purpose of this original study is to determine the recommended phase 2 dose (RP2D) of TAK-079 when administered to participants with NDMM in combination with the backbone treatment regimen. The purpose of the safety/access cohort is to provide continued access to TAK-079 to participants previously enrolled to a TAK-079 parent study and to evaluate the long-term safety profile of TAK-079.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: TAK-079 Drug: Lenalidomide Drug: Dexamethasone Drug: Bortezomib Drug: Pomalidomide Phase 1

Detailed Description:

Treatment phase drug being tested in this study is called TAK-079. TAK-079 is being tested to evaluate the safety, tolerability, efficacy, and pharmacokinetic (PK) when added to 1 of 2 standard backbone regimens (LenDex or VRd) with newly diagnosed NDMM for whom stem cell transplantation (SCT) is not planned as initial therapy.

The study will enroll approximately 36 participants. Participants will be non-randomly assigned to one of the two treatment groups in the original study or Treatment Phase:

  • TAK-079 and LenDex
  • TAK-079 and VRd

All enrolled participants will have the opportunity to complete the treatment therapy and then enter the Extension study for as long as participants continue to derive benefit. Safety Extension Phase participants who have previously received and tolerated TAK-079-based parent study will continue to the extension study. The study will also evaluate the long-term safety profile of TAK-079. Participants will continue to receive TAK-079 and, if applicable, SOC backbone therapy as per the parent study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter Phase 1b Study Investigating the Safety of TAK-079 in Combination With Backbone Regimens for the Treatment of Patients With Newly Diagnosed Multiple Myeloma and for Whom Stem Cell Transplantation Is Not Planned as Initial Therapy
Actual Study Start Date : July 29, 2019
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : March 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Treatment Phase: TAK-079 and LenDex
TAK-079, subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with lenalidomide, orally, once daily for 21 days and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until progressive disease (PD) or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are greater than (>) 75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy.
Drug: TAK-079
TAK-079 subcutaneously.
Other Name: Mezagitamab

Drug: Lenalidomide
Lenalidomide orally.

Drug: Dexamethasone
Dexamethasone orally.

Drug: Pomalidomide
Pomalidomide orally.

Experimental: Treatment Phase: TAK-079 and VRd
TAK-079 subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with bortezomib, subcutaneously, once on Days 1, 8, and 15, for a maximum of 8 cycles, lenalidomide, orally, once daily for 21 days, and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until PD or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are >75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy.
Drug: TAK-079
TAK-079 subcutaneously.
Other Name: Mezagitamab

Drug: Lenalidomide
Lenalidomide orally.

Drug: Dexamethasone
Dexamethasone orally.

Drug: Bortezomib
Bortezomib subcutaneously.

Drug: Pomalidomide
Pomalidomide orally.

Experimental: Safety Extension Phase: TAK-079 and, if applicable, backbone therapy (LenDex, VRd, or PomDex)
TAK-079 dosing and, if applicable, backbone therapy will be administered as per the schedule outlined in the parent study.
Drug: TAK-079
TAK-079 subcutaneously.
Other Name: Mezagitamab

Drug: Lenalidomide
Lenalidomide orally.

Drug: Dexamethasone
Dexamethasone orally.

Drug: Bortezomib
Bortezomib subcutaneously.

Drug: Pomalidomide
Pomalidomide orally.




Primary Outcome Measures :
  1. Treatment Phase: RP2D of TAK-079 [ Time Frame: Up to Cycle 1 (Cycle length is equal to [=] 28 days) ]
    RP2D of TAK-079 along with lenalidomide-dexamethasone (LenDex) or TAK-079 along with bortezomib, lenalidomide, and dexamethasone (VRd) will be based on number of participants with dose limiting toxicity (DLT). DLTs will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

  2. Safety Extension Phase: Number of Participants Reporting one or More Serious Adverse Events (SAEs) [ Time Frame: From first dose up to 30 days after the last dose of study drug (up to 4 years) ]
  3. Safety Extension Phase: Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From first dose up to 30 days after the last dose of study drug (up to 4 years) ]
    Adverse event (AE) Grades will be evaluated as per NCI CTCAE, version 4.03.

  4. Safety Extension Phase: Number of Participants Who Require Dose Modification [ Time Frame: From first dose up to 30 days after the last dose of study drug (up to 4 years) ]
  5. Safety Extension Phase: Number of Participants With TEAEs Leading to Treatment Discontinuation [ Time Frame: From first dose up to 30 days after the last dose of study drug (up to 4 years) ]

Secondary Outcome Measures :
  1. Treatment Phase: Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]
    ORR based on International Myeloma Working Group (IMWG) Uniform Response Criteria, is defined as the percentage of participants who achieved a PR or better during the study. PR is defined as greater than or equal to (>=) 50 percent (%) reduction of serum M-protein, and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 milligram per 24 hours (mg/24 h). If serum and urine M protein are not measurable, >=50% decrease in difference between involved and uninvolved free light chain (FLC) levels is required in place of M protein criteria.

  2. Treatment Phase: Number of Participants Reporting one or More TEAEs and SAEs [ Time Frame: From first dose up to 30 days after the last dose of study drug (up to 2 years) ]
  3. Treatment Phase: Number of Participants With Grade 3 or Higher TEAEs [ Time Frame: From first dose up to 30 days after the last dose of study drug (up to 2 years) ]
    AE Grades will be evaluated as per NCI CTCAE, version 4.03.

  4. Treatment Phase: Number of Participants with TEAEs Leading to Treatment Discontinuation [ Time Frame: From first dose up to 30 days after the last dose of study drug (up to 2 years) ]
  5. Treatment Phase: Number of Participants With AEs Leading to On-study Deaths [ Time Frame: From screening up to 30 days after the last dose of study drug (up to 2 years) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion (Inc) Criteria:

  1. Must have previously untreated multiple myeloma (MM) as defined by the IMWG criteria requiring treatment according to the investigator.
  2. Are appropriate candidates for either the VRd or Rd backbone antimyeloma therapy according to the investigator.
  3. Must have measurable disease defined by at least 1 of the following:

    • Serum M-protein >=1 gram per deciliter (g/dL) (>=10 gram/liter [g/L]).
    • Urine M-protein >=200 mg/24 hours.
    • Serum FLC assay: involved FLC level >=10 mg/dL (>=100 milligram per liter [mg/L]) provided the serum FLC ratio is abnormal.
  4. Participants receiving lenalidomide must be able to take concurrent prophylactic anticoagulation per standard clinical practice as directed by the investigator.
  5. Life expectancy >3 months.
  6. Eastern Cooperative Oncology Group (ECOG) performance status score less than or equal to (<=) 2.

Inc Criteria for Participants in the Safety/Access Cohort (only):

Participants previously treated with TAK-079 therapy in a Takeda-sponsored TAK-079 parent study. Participants will be eligible to enter this cohort when:

1. The parent study is closed, planned to be closed, or has met its primary objectives.

Exclusion (Exc) Criteria:

  1. Prior systemic therapy for MM.

    o treatment with bisphosphonates or a single course of glucocorticoids does not disqualify the participant (the maximum dose of corticosteroids should not exceed the equivalent of 160 mg [for example, 40 milligram per day (mg/d) for 4 days] of dexamethasone).

  2. Current participation in another interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device) within 4 weeks of the first dose of TAK-079 or any agent in the backbone regimen and throughout the duration of this trial.
  3. Prior radiation therapy within 14 days of the first dose of TAK-079 or any backbone regimen agents.

    NOTE: Prophylactic localized ("spot") radiation for areas of pain is allowed.

  4. Major surgery within 4 weeks before Cycle 1 Day 1 (kyphoplasty is not considered major surgery). Participants should be fully recovered from any surgically related complications.
  5. Plasmapheresis within 28 days of randomization.
  6. If plasmacytoma is the only measurable parameter for assessing disease response, participant is not eligible because of difficult response evaluation.
  7. Clinical signs of meningeal involvement of MM exhibited during screening.
  8. Serum positive for human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  9. Known severe allergic or anaphylactic reactions to human recombinant proteins or excipients used in the TAK-079 formulation or agents in the backbone regimen (lenalidomide, bortezomib, dexamethasone) as per the respective prescribing information or for TAK-079, as outlined in the current investigator's brochure (IB).
  10. Systemic infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of TAK-079 or any agent in the backbone regimen. Urinary tract infection is not considered a systemic infection.
  11. A 12-lead electrocardiogram (ECG) showing a QT interval corrected by Frederica's formula (QTcF) >470 milliseconds. If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG.
  12. Diagnosis of primary amyloidosis, Waldenstrom's disease, monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) per IMWG criteria or standard diagnostic criteria, plasma cell leukemia (according to the World Health Organization [WHO] criterion: >=20% of cells in the peripheral blood with an absolute plasma cell count of more than 2 *10^9/L), polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS syndrome), myelodysplastic syndrome, or myeloproliferative syndrome.
  13. History of myelodysplastic syndrome or another malignancy other than MM, except for the following: any malignancy that has been in complete remission for 2 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer (Gleason score <=6 without known metastatic disease and with no requirement for therapy, or requiring only hormonal therapy and stable prostate-specific antigen for >=1 year before initiation of study therapy), breast carcinoma in situ with full surgical resection, and treated medullary or papillary thyroid cancer.

Exc Criteria for Participants in the Safety/Access Cohort

1. Participants meeting any of the criteria for treatment discontinuation in the parent study.


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): NCT03984097


Locations
Layout table for location information
United States, Alabama
Alabama Oncology
Birmingham, Alabama, United States, 35211
United States, California
Pacific Cancer Care
Monterey, California, United States, 93940
United States, Maryland
American Oncology Partners of Maryland, PA
Bethesda, Maryland, United States, 20817
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
United States, Ohio
Good Samaritan Hospital
Cincinnati, Ohio, United States, 45220
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
Froedtert Hospital & the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Takeda
Investigators
Layout table for investigator information
Study Director: Study Director Takeda
Additional Information:
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03984097    
Other Study ID Numbers: TAK-079-1002
U1111-1230-4820 ( Registry Identifier: WHO )
First Posted: June 12, 2019    Key Record Dates
Last Update Posted: August 5, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://vivli.org/ourmember/takeda/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda:
Drug Therapy
TAK-079
CD38
Monoclonal Antibody
Lenalidomide
Bortezomib
Pomalidomide
Velcade
Stem Cell Transplant
Neoplasms, Plasma Cell
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Lenalidomide
Bortezomib
Pomalidomide
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors