Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Investigate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of TAK-573 in Participants With Refractory Multiple Myeloma (MM)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03215030
Recruitment Status : Recruiting
First Posted : July 12, 2017
Last Update Posted : October 7, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
The purpose of this study is to determine the safety and tolerability of single agent TAK-573 in participants with relapsed/refractory MM in Phase 1, and to provide a preliminary evaluation of the clinical activity of TAK-573 as a single agent and in combination with dexamethasone in participants with relapsed/refractory MM in Phase 2.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: TAK-573 Drug: Dexamethasone Phase 1 Phase 2

Detailed Description:

The drug being tested in this study is called TAK-573 as single agent and in combination with dexamethasone. The study will determine the safety and tolerability of TAK-573 as single agent and in combination with dexamethasone in participants with relapsed/refractory MM. The study consists of 2 Phases, 1 and 2.

The study will enroll approximately 51 and 100 participants in Phase 1 and 2 respectively. Participants will be randomly assigned to one of the following treatment groups in each Phase:

  • Phase 1 Schedule A: TAK-573 0.001 to 14 mg/kg
  • Phase 1 Schedule B: TAK-573 TBD
  • Phase 1 Schedule C: TAK-573 TBD
  • Phase 1 Schedule D: TAK-573 TBD
  • Phase 2: TAK-573 TBD

The Phase 1 portion of the study will follow a 3+3 dose escalation design to evaluate once-weekly up to 4 different schedules of administration of TAK-573 starting at 0.001 mg/kg for DLT evaluation and to determine the maximum tolerated dose (MTD) or an optimal biological dose (OBD) for assessments in Phase 2.

This multi-center trial will be conducted in the United States. The maximum treatment duration in this study is up to 12 months and overall time to participate in the study is approximately up to 40 months. Participants will make 37 visits to the clinic, and will be contacted every 12 weeks for post treatment follow-up. Participants will be followed up for survival until death, lost to follow-up, consent withdrawal, or study termination by the sponsor, whichever occurs first.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 151 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-label Study to Investigate the Safety and Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of TAK-573 as a Single Agent in Patients With Refractory Multiple Myeloma
Actual Study Start Date : October 4, 2017
Estimated Primary Completion Date : October 8, 2021
Estimated Study Completion Date : October 8, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Phase 1 Schedule A: TAK-573 0.001 to 14 mg/kg
TAK-573 0.001 to 14 milligram per kilogram (mg/kg), infusion, intravenously, once on Days 1, 8, 15 and 22 of each 28-day treatment cycle up to 2 cycles, followed by once on Days 1 and 15 of each 28-day treatment cycle up to 4 cycles, followed by once on Day 1 of each 28-day treatment cycle until treatment discontinuation.
Drug: TAK-573
TAK-573 intravenous infusion.
Other Name: TEV-48573

Experimental: Phase 1 Schedule B: TAK-573 TBD
TAK-573 TBD, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information.
Drug: TAK-573
TAK-573 intravenous infusion.
Other Name: TEV-48573

Experimental: Phase 1 Schedule C: TAK-573 TBD
TAK-573 TBD, infusion, intravenously, once on Day 1 of each 21-day treatment cycle u until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information.
Drug: TAK-573
TAK-573 intravenous infusion.
Other Name: TEV-48573

Experimental: Phase 1 Schedule D: TAK-573 TBD
TAK-573 TBD, infusion, intravenously, once on Day 1 of each 28-day treatment cycle until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information.
Drug: TAK-573
TAK-573 intravenous infusion.
Other Name: TEV-48573

Experimental: Phase 2: TAK-573 TBD
Dose for Phase 2 will be based on safety and tolerability results from the preceding Phase 1 dose escalation cohorts. Participants in Phase 2 cohorts will receive TAK-573 TBD as a single agent. Participants in at least 1 cohort will receive TAK-573 TBD and dexamethasone 40 mg, orally, once weekly of each 28-day treatment cycle until treatment discontinuation.
Drug: TAK-573
TAK-573 intravenous infusion.
Other Name: TEV-48573

Drug: Dexamethasone
Dexamethasone.




Primary Outcome Measures :
  1. Phase 1- Percentage of Participants Reporting one or More TEAEs, Serious Adverse Events, >=Grade 3 TEAEs, Dose Modification, Adverse Events Leading to Discontinuation of Study Drug, Clinically Significant Laboratory Values and Vital Signs [ Time Frame: Up to 1 year ]
    Treatment-emergent Adverse Events (TEAEs) Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (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 adverse event (AE).

  2. Phase 2- Overall Response Rate (ORR) [ Time Frame: Up to 1 year ]
    ORR is defined as the percentage of participants who achieved a partial response rate (PR) or better during the study as defined by International Myeloma Working Group (IMWG) Uniform Response Criteria.

  3. Phase 2- Duration of Response (DOR) [ Time Frame: Up to 1 year ]
    DOR is defined as the time from the date of first documentation of response to the date of first documentation of progressive disease (PD) as defined by IMWG Criteria.

  4. Phase 2- Progression-free Survival (PFS) [ Time Frame: Up to 1 year ]
    PFS is defined as the time from the date of enrollment until the date of PD or death due to any cause, whichever occurs first as defined by IMWG Criteria.

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

  6. Phase 2- Time to Response [ Time Frame: Up to 1 year ]
    Time to response is defined as the time from first dose to the date of first documentation of response (PR or better) as defined by IMWG Criteria.

  7. Phase 1- Percentage of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: Up to Cycle 1 (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) ]
    DLTs will be evaluated as per NCI CTCAE, version 4.03.


Secondary Outcome Measures :
  1. Cmax: Maximum Observed Serum Concentration for TAK-573 [ Time Frame: Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) ]
    PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 336h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

  2. Tmax: Time to Reach the Cmax for TAK-573 [ Time Frame: Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) ]
    PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 336h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

  3. AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for TAK-573 [ Time Frame: Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) ]
    PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 336h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

  4. AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for TAK-573 [ Time Frame: Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) ]
    PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 336h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

  5. λz: Terminal Disposition Rate Constant for TAK-573 [ Time Frame: Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) ]
    PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 336h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

  6. T1/2: Terminal Elimination Half-life for TAK-573 [ Time Frame: Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) ]
    PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 336h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

  7. CL: Clearance for TAK-573 [ Time Frame: Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) ]
    PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 336h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

  8. Vss: Volume of Distribution at Steady State for TAK-573 [ Time Frame: Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) ]
    PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 336h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days).

  9. Phase 1- ORR [ Time Frame: Up to 1 year ]
    ORR is defined as the percentage of participants who achieved a PR or better during the study as defined by IMWG Uniform Response Criteria.

  10. Phase 1- DOR [ Time Frame: Up to 1 year ]
    DOR is defined as the time from the date of first documentation of response to the date of first documentation of PD as defined by IMWG Criteria.

  11. Phase 1- PFS [ Time Frame: Up to 1 year ]
    PFS is defined as the time from the date of enrollment until the date of PD or death due to any cause, whichever occurs first as defined by IMWG Criteria.

  12. Phase 1- OS [ Time Frame: Time Frame: Up to 1 year ]
    OS is defined as the date of first dose to the date of death due to any cause.

  13. Phase 1- Time to Response [ Time Frame: Up to 1 year ]
    Time to response is defined as the time from first dose to the date of first documentation of response (PR or better) as defined by IMWG Criteria.

  14. Percentage of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (nAb) [ Time Frame: Up to 1 year ]
  15. Phase 2- Percentage of Participants Reporting one or More TEAEs, Dose Modification, Leading to Discontinuation of Study Drug, DLT-like, Clinically Significant Laboratory Values and Vital Signs [ Time Frame: Up to 1 year ]
    TEAEs and DLT-like will be evaluated as per NCI CTCAE, version 4.03.



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 Criteria:

  1. Has MM defined by the IMWG criteria with evidence of disease progression and:

    • In need of additional myeloma therapy as determined by the investigator.
    • Has previously received at least 3 lines of myeloma therapy (example, containing an Immunomodulatory imide drug [IMid], a proteasome inhibitor [PI], an alkylating agent, and/or an anti-CD38 as single agents or in combination).
    • Has either refractory to or intolerant of at least one proteasome inhibitor and a least one immunomodulatory drug.
  2. For participants in MTD/OBD cohort expansion and Phase 2 only: participant has measurable disease.
  3. During dose escalation only, participants not meeting the above criteria for measurable disease should, at least, have measurable bone marrow plasmacytosis (greater than or equal to [>=] 10 percent [%]) and/or plasmacytoma (>=1 centimeter [cm] in diameter) detected by physical examination or imaging.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Exclusion Criteria:

  1. Has polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenstrom macroglobinemia or immunoglobulin M (IgM) myeloma, or lymphoplasmacytic lymphoma (LPL).
  2. Has sensory or motor neuropathy of NCI CTCAE >=Grade 3.
  3. Who have received autologous stem cell transplant (SCT) 60 days before first infusion of TAK-573 or participants who have received allogeneic SCT 6 months before first infusion. Graft-versus-host disease that is active or requires ongoing systemic immunosuppression.
  4. Has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE less than or equal to (<=) Grade 1 or baseline, except for sensory or motor neuropathy which should have recovered to <=Grade 2 or baseline.
  5. Has clinical signs of central nervous system involvement of MM.

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): NCT03215030


Contacts
Layout table for location contacts
Contact: Takeda Study Registration Call Center +1-844-662-8532 GlobalOncologyMedinfo@takeda.com

Locations
Layout table for location information
United States, Georgia
Winship Cancer Institute of Emory University Not yet recruiting
Atlanta, Georgia, United States, 30322
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43202
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
Swedish Medical Center Not yet recruiting
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Layout table for investigator information
Study Director: Medical Director Clinical Science Millennium Pharmaceuticals, Inc.

Layout table for additonal information
Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03215030     History of Changes
Other Study ID Numbers: TAK-573-1501
TV48573-ONC-10128 ( Other Identifier: Former Id )
U1111-1195-8134 ( Registry Identifier: WHO )
First Posted: July 12, 2017    Key Record Dates
Last Update Posted: October 7, 2019
Last Verified: October 2019
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 for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com 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.

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 ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy
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
Dexamethasone acetate
BB 1101
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
Protease Inhibitors
Enzyme Inhibitors