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A Study to Investigate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of TAK-079 Administered Subcutaneously as a Single Agent in Participants With Relapsed/Refractory (r/r) Multiple Myeloma (MM)

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ClinicalTrials.gov Identifier: NCT03439280
Recruitment Status : Recruiting
First Posted : February 20, 2018
Last Update Posted : September 17, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
The purpose of this study is to assess the safety, tolerability, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) in Phase 1 of the study and to provide a preliminary evaluation of the clinical activity of TAK-079 monotherapy in participants with r/r MM in Phase 2a of the study.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Multiple Myeloma Drug: TAK-079 Phase 1 Phase 2

Detailed Description:

The drug being tested in this study is called TAK-079. TAK-079 is being tested to treat people who have r/r MM. This study will assess the safety, tolerability, efficacy, pharmacokinetics, and immunogenicity of TAK-079 monotherapy and will provide a preliminary assessment of its activity against MM. The study is designed to consist of 2 phases: Phase 1 and Phase 2a.

The study will enroll approximately 42 participants. The study population of Phase 1 will consist of approximately 24 participants. Participants in Phase 1 will be assigned to TAK-079 and dose-escalation will range from 45 mg to 1800 mg.

In Phase 1, participants will receive premedications 1 to 3 hours prior to the administration of TAK-079 on each dosing day, as follows:

  • Dexamethasone 20 mg
  • Acetaminophen 650 to 1000 mg
  • Diphenhydramine 25 to 50 mg
  • Montelukast 10 mg

The study population of Phase 2a will consist of approximately 18 participants. Dose and premedications for Phase 2a will be based upon review of the available safety, efficacy, pharmacokinetic, and pharmacodynamic data from the preceding cohorts of Phase 1.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is 48 months (4 years). In Phase 1, participants who stop treatment for any other reason other than PD will continue to have progression-free survival (PFS) follow-up at the site every 4 weeks from the last dose of study drug up to 12 months or until PD, death, loss to follow-up, consent withdrawal or study termination. Participants will be followed 30 days after last dose of study drug or until the start of subsequent alternative anti-cancer therapy, whichever occurs first, for a follow up assessment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase 1/2a Open-label, Dose-Escalation Study to Investigate the Safety and Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of TAK-079 Administered Subcutaneously as a Single Agent in Patients With Relapsed/Refractory Multiple Myeloma
Actual Study Start Date : April 26, 2018
Estimated Primary Completion Date : October 28, 2020
Estimated Study Completion Date : October 28, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Phase 1 Cohort 1: TAK-079
TAK-079, injection, subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter in a 28-day treatment cycle until PD, unacceptable toxicities or withdrawal due to other reasons. Dose escalation of TAK-079 will range from 45 milligram (mg) to 1800 mg and may be done using a 3 + 3 dose escalation design to determine a MTD and/or RP2D.
Drug: TAK-079
TAK-079 injection.

Experimental: Phase 2a: TAK-079 TBD
TAK-079, injection, subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter in a 28-day treatment cycle until PD, unacceptable toxicities or withdrawal due to other reasons. TAK-079 dose for this phase will be determined based on review of the available safety, efficacy, pharmacokinetic, and pharmacodynamic data obtained from the Phase 1 portion of the study.
Drug: TAK-079
TAK-079 injection.




Primary Outcome Measures :
  1. Phase 1: Number of Participants Reporting one or more Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to 1 year ]
  2. Phase 1: Number of Participants with Dose-limiting Toxicities (DLTs) [ Time Frame: Up to 1 year ]
    DLTs will be defined as any of the following events: Grade 4 laboratory abnormalities, except those events that are clearly due to extraneous causes; nonhematologic TEAEs of grade greater than or equal to (>=3) except grade 3 nausea/vomiting, fatigue lasting less than 72 hours, elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) that resolves to grade less than or equal to (<=)1 or baseline within 7 days, injection reaction (IR) that responds to symptomatic treatment; Hematologic TEAEs of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade >=4, except grade >=3 hemolysis, grade 3 low platelet or higher count with clinically meaningful bleeding; and an incomplete recovery from treatment-related toxicity causing a greater than (>) 2-week delay in the next scheduled injection before the initiation of Cycle 2 will be considered a DLT.

  3. Phase 1: Number of Participants with Grade 3 or Higher TEAEs [ Time Frame: Up to 1 year ]
    AE Grades will be evaluated as per NCI CTCAE, version 4.03. Grade 1 scaled as Mild; Grade 2 scaled as Moderate; Grade 3 scaled as severe or medically significant but not immediately life-threatening; Grade 4 scaled as life-threatening consequences; and Grade 5 scaled as death related to AE.

  4. Phase 1: Number of Participants with Serious TEAEs [ Time Frame: Up to 1 year ]
  5. Phase 1: Number of Participants with TEAEs Leading to Treatment Discontinuation [ Time Frame: Up to 1 year ]
  6. Phase 1: Number of Participants with TEAEs Leading to Dose Modifications [ Time Frame: Up to 1 year ]
  7. Phase 1: Number of Participants with Clinically Significant Laboratory Values [ Time Frame: Up to 1 year ]
  8. Phase 1: Number of Participants with Clinically Significant Vital Sign Measurements [ Time Frame: Up to 1 year ]
  9. Phase 2a: Overall Response Rate (ORR) [ Time Frame: Up to 1 year ]
    ORR is defined as the percentage of participants who achieved a partial response (PR) of 50 percent (%) tumor reduction or better during the study. PR is defined as >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90% or to less than (<) 200 milligram per (mg/) 24 hours.


Secondary Outcome Measures :
  1. Cmax: Maximum Observed Serum Concentration for TAK-079 [ Time Frame: Cycle 1 and 2: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose ]
  2. Tmax: Time to Reach the Maximum Observed Serum Concentration (Cmax) for TAK-079 [ Time Frame: Cycle 1 and 2: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose ]
  3. AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for TAK-079 [ Time Frame: Cycle 1 and 2: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose ]
  4. Phase 1: ORR [ Time Frame: Up to 1 year ]
    ORR is defined as the percentage of participants who achieved a PR of 50% tumor reduction or better during the study. PR is defined as >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours.

  5. Percentage of Participants with Minimal Response (MR) [ Time Frame: Up to 1 year ]
    MR is defined as >=25% but <=49% reduction of serum M-protein and reduction in 24-hour urine M-protein by 50% to 89%.

  6. Percentage of Participants With Positive Anti-drug Antibodies (ADA) [ Time Frame: Up to 1 year ]
  7. Phase 2a: Number of Participants with DLTs [ Time Frame: Up to 1 year ]
  8. Phase 2a: Number of Participants Reporting one or more TEAEs [ Time Frame: Up to 1 year ]
  9. Phase 2a: Number of Participants with TEAEs Leading to Dose Modifications [ Time Frame: Up to 1 year ]
  10. Phase 2a: Number of Participants with TEAEs Leading to Treatment Discontinuation [ Time Frame: Up to 1 year ]
  11. Phase 2a: Number of Participants with Clinically Significant Laboratory Values [ Time Frame: Up to 1 year ]
  12. Phase 2a: Number of Participants with Clinically Significant Vital Sign Measurements [ Time Frame: Up to 1 year ]
  13. Phase 2a: Duration of Response (DOR) [ Time Frame: Up to 1 year ]
    DOR is the time from date of first documentation of response to date of first documented PD. PD is increase of >=25% from lowest response value in any of following:Serum M-protein(increase must be >=0.5 gram per decilitre[g/dL];serum M component increases >=1 g/dL are sufficient to define relapse if starting M component is >=5 g/dL),and/or urine M-protein(increase must be >=200 mg/24 hour), and/or only in participants without measurable serum and urine M-protein levels, difference between involved/uninvolved free light chain (FLC) levels (increase must be >10 mg/dL), and only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cell percentage (percentage must be >=10%) or definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or soft tissue plasmacytomas, and development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.

  14. Phase 2a: Progression Free Survival (PFS) [ Time Frame: Up to 1 year ]
    PFS is time from the date of the first dose until the earliest date of disease progression (PD). PD is increase of >=25% from lowest response value in any of following: Serum M-protein (increase must be >=0.5 g/dL; serum M component increases >=1 g/dL are sufficient to define relapse if starting M component is >=5 g/dL),and/or urine M-protein (increase must be >=200 mg/24 hour), and/or only in participants without measurable serum and urine M-protein levels, difference between involved/uninvolved FLC levels (increase must be >10 mg/dL), and only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cell percentage (percentage must be >=10%) or definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or soft tissue plasmacytomas, and development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.

  15. Phase 2a: Overall Survival (OS) [ Time Frame: Up to 1 year ]
    OS is defined as the time from the date of first dose to the date of death due to any cause.

  16. Phase 2a: Time to Response (TTR) [ Time Frame: Up to 1 year ]
    TTR is defined as the time from the date of the first dose to the date of the first documentation of response (PR [partial response] or better). PR is defined as >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours.



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

Inclusion Criteria:

  1. Eastern Cooperative Oncology Group (ECOG) performance status of <=2.
  2. Has received previous myeloma-specific therapy.
  3. Requires additional therapy, as determined by the investigator.
  4. Documentation of r/r MM as defined by the International Myeloma Working Group (IMWG) criteria.
  5. For Participants with MM, measurable disease defined as one of the following:

    • Serum M-protein >=500 mg/dL (>=5 gram per liter [g/L]).
    • Urine M-protein >=200 mg/24 hours.
    • In participants without measurable M-protein in serum protein electrophoresis (SPEP) or urine protein electrophoresis (UPEP), a serum FLC assay result with involved FLC level >=10 mg/dL (>=100 milligram per liter [mg/L]), provided serum FLC ratio is abnormal.
  6. Prior therapy should include at least a proteasome inhibitor (PI), an immunomodulatory drug (IMid), an alkylating agent, and a steroid and should be refractory or intolerant to at least 1 PI and at least 1 IMid.

Note:

o Refractory is defined as at least a 25% increase in M-protein or PD during treatment or within 60 days after cessation of treatment.

Exclusion Criteria:

  1. Sensory or motor neuropathy of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade >=3.
  2. Have received allogeneic stem cell transplant.
  3. Have received anti-CD38 antibody therapy and do not fulfill a 120-day washout period before receiving TAK-079.
  4. Not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE Grade <=1 or baseline.
  5. Clinical signs of central nervous system (CNS) involvement of MM.
  6. Active chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, active HIV, or cytomegalovirus (CMV) infection.
  7. POEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, or IgM myeloma.
  8. Positive Coombs tests at screening.

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): NCT03439280


Contacts
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Contact: Takeda Study Registration Call Center +1-866-835-2233 globaloncologymedinfo@takeda.com

Locations
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United States, California
City of Hope - Duarte Recruiting
Duarte, California, United States, 91010-3012
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Mount Sinai Hospital-The Donald H. Ruttenberg Cancer Treatment Center Recruiting
New York, New York, United States, 10011
Weill Cornell Medical Center, Div. of Hematology Medical Oncology Recruiting
New York, New York, United States, 10021-4635
United States, Oregon
Oregon Health & Science University Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Texas Oncology - San Antonio Northwest Recruiting
San Antonio, Texas, United States, 78217
United States, Virginia
Virginia Cancer Specialists - Fairfax Office Recruiting
Fairfax, Virginia, United States, 22031
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Director Takeda

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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03439280     History of Changes
Other Study ID Numbers: TAK-079-1501
U1111-1208-3202 ( Other Identifier: WHO )
First Posted: February 20, 2018    Key Record Dates
Last Update Posted: September 17, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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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 Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug therapy

Additional relevant MeSH terms:
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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