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A Study of TAK-169 in Participants With Relapsed or Refractory Multiple Myeloma

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: NCT04017130
Recruitment Status : Recruiting
First Posted : July 12, 2019
Last Update Posted : February 18, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE July 10, 2019
First Posted Date  ICMJE July 12, 2019
Last Update Posted Date February 18, 2021
Actual Study Start Date  ICMJE February 5, 2020
Estimated Primary Completion Date January 17, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2020)
  • Part 1: Number of Participants With Overall and per Dose Level Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to 12 months ]
  • Part 1: Number of Participants With Dose-limiting Toxicities (DLTs) at Each Dose Level [ Time Frame: Up to 12 months ]
    DLTs is defined as any of the events that are considered by the investigator to be at least possibly related to therapy with the study medication. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0).
  • Part 1: Number of Participants With Grade Greater Than or Equal to (>=) 3 TEAEs [ Time Frame: Up to 12 months ]
    Grade >=3 TEAEs will be evaluated according to NCI CTCAE 5.0.
  • Part 1: Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 12 months ]
  • Part 1: Number of Participants Who Discontinued TAK-169 Due to TEAEs [ Time Frame: Up to 12 months ]
  • Part 1: Number of Participants With Treatment Related Dose Modifications Including Dose Delays, Dose interruption and Dose Reductions [ Time Frame: Up to 12 months ]
  • Part 2: Overall Response Rate (ORR) [ Time Frame: Up to 12 months ]
    Percentage of participants who achieved a partial response (PR) or better during study as defined by International Myeloma Working Group (IMWG) Uniform Response Criteria. PR is >=50 percent (%) reduction of serum M protein and reduction in 24-hour urinary M protein by >=90% or less than (<) 200 milligram per (mg/) 24 hour (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. If serum and urine M protein and serum FLC assay are not measurable, >=50% reduction in bone marrow plasma cells is required in place of M protein, provided baseline percentage was >=30%. In addition, if present at baseline, >=50% reduction in size of soft tissue plasmacytomas is required. Two consecutive assessments are needed; no known evidence of progressive or new bone lesions if radiographic studies were performed.
Original Primary Outcome Measures  ICMJE
 (submitted: July 10, 2019)
  • Part 1: Number of Participants With Overall and per Dose Level Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to 12 months ]
  • Part 1: Number of Participants With Dose-limiting Toxicities (DLTs) at Each Dose Level [ Time Frame: Up to 12 months ]
    DLTs is defined as any of the events that are considered by the investigator to be at least possibly related to therapy with the study medication. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0).
  • Part 1: Number of Participants With Grade Greater Than or Equal to (>=) 3 TEAEs [ Time Frame: Up to 12 months ]
    Grade >=3 TEAEs will be evaluated according to NCI CTCAE 5.0.
  • Part 1: Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 12 months ]
  • Part 1: Number of Participants Who Discontinued TAK-169 Due to TEAEs [ Time Frame: Up to 12 months ]
  • Part 1: Number of Participants With Treatment Related Dose Modifications Including Dose Delays, Dose interruption and Dose Reductions [ Time Frame: Up to 12 months ]
  • Part 1: Number of Participants With Clinically Significant Change in Laboratory Values [ Time Frame: Up to 12 months ]
  • Part 1: Number of Participants With Clinically Significant Change in Vital Sign Measurements [ Time Frame: Up to 12 months ]
  • Part 2: Overall Response Rate (ORR) [ Time Frame: Up to 12 months ]
    Percentage of participants who achieved a partial response (PR) or better during study as defined by International Myeloma Working Group (IMWG) Uniform Response Criteria. PR is >=50 percent (%) reduction of serum M protein and reduction in 24-hour urinary M protein by >=90% or less than (<) 200 milligram per (mg/) 24 hour (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. If serum and urine M protein and serum FLC assay are not measurable, >=50% reduction in bone marrow plasma cells is required in place of M protein, provided baseline percentage was >=30%. In addition, if present at baseline, >=50% reduction in size of soft tissue plasmacytomas is required. Two consecutive assessments are needed; no known evidence of progressive or new bone lesions if radiographic studies were performed.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2019)
  • Part 1 and Part 2, Cmax: Maximum Observed Concentration for TAK-169 [ Time Frame: Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days) ]
  • Part 1 and Part 2, Tmax: Time to Reach the Maximum Observed Concentration (Cmax) for TAK-169 [ Time Frame: Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days) ]
  • Part 1 and Part 2, AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-169 [ Time Frame: Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days) ]
  • Part 1: ORR [ Time Frame: Up to 12 months ]
    Percentage of participants who achieved PR or better during study as defined by IMWG Uniform Response Criteria. PR is >=50 % reduction of serum M protein and reduction in 24-hour urinary M protein by >=90% or <200 mg/24 h. If serum and urine M protein are not measurable, >=50% decrease in difference between involved and uninvolved FLC levels is required in place of M protein criteria. If serum and urine M protein and serum FLC assay are not measurable, >=50% reduction in bone marrow plasma cells is required in place of M protein, provided baseline percentage was >=30%. In addition, if present at baseline, >=50% reduction in size of soft tissue plasmacytomas is required. Two consecutive assessments are needed; no known evidence of progressive or new bone lesions if radiographic studies were performed.
  • Part 1: Clinical Benefit Rate (CBR) [ Time Frame: Up to 12 months ]
    CBR is defined as the percentage of participants who achieved a minimal response (MR) or better during study as defined by IMWG Uniform Response Criteria. MR is defined as a >=25% but less than or equal to (<=) 49% reduction of serum M protein and reduction in 24-hour urine M protein by 50% to 89%. In addition, if present at baseline, 25% to 49% reduction in size of soft tissue plasmacytomas is also required. No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).
  • Part 1 and Part 2: Progression-free Survival (PFS) [ Time Frame: From date of the dose administration until death due to any cause (up to 12 months) ]
    PFS: time from the date of first dose until the date of progressive disease (PD), by IMWG criteria, or the date of death due to any cause. PD: Increase of 25% from lowest response value in: Serum M component with absolute increase >=0.5 gram per deciliter (g/dL); serum M component increases >=1 g/dL, to define relapse if starting M component >=5 g/dL; Urine M component(absolute increase >=200 mg/24 h); Only in participants without measurable serum and urine M protein levels: difference between involved and uninvolved FLC levels(absolute increase >10 milligram per deciliter [mg/dL]); Only in participants without measurable serum and urine M protein levels and without measurable disease by FLC level, bone marrow plasma cell% (absolute% >=10%); Development of new or definite increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia may attributed solely to plasma cell proliferative disorder; Two consecutive assessments before new therapy needed.
  • Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: From the date of the first documentation of response to the date of the first documented PD (up to 12 months) ]
    DOR is time from the date of the first documentation of response to the date of the first documented PD. PD is increase of 25% from lowest response value in: Serum M component with absolute increase >=0.5 g/dL; serum M component increases >=1g/dL, to define relapse if starting M component >=5 g/dL; Urine M component(absolute increase >=200 mg/24 h); Only in participants without measurable serum and urine M protein levels:difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL); Only in participants without measurable serum and urine M protein levels and without measurable disease by FLC level, bone marrow plasma cell% (absolute% >=10%); Development of new or definite increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder; Two consecutive assessments before new therapy needed.
  • Part 1 and Part 2: Percentage of Participants who Achieved MR [ Time Frame: Up to 12 months ]
    Percentage of participants who achieved MR, defined as 25% tumor reduction. MR is defined as a >=25% but <=49% reduction of serum M protein and reduction in 24-hour urine M protein by 50% to 89% as defined by IMWG Uniform Response Criteria.
  • Part 1 and Part 2: Number of Participants With Anti-drug Antibodies Following Administration of TAK-169 [ Time Frame: Up to 12 months ]
  • Part 2: Number of Participants With DLTs and Other TEAEs Including Dose Modifications, Treatment Discontinuation, and Vital signs [ Time Frame: Up to 12 months ]
    DLTs is defined as any of the events that are considered by the investigator to be at least possibly related to therapy with the study medication. Toxicity will be evaluated according to NCI CTCAE 5.0.
  • Part 2: Overall Survival (OS) [ Time Frame: From date of the dose administration until death due to any cause (up to 12 months) ]
    OS is defined as time from date of the dose administration until death due to any cause.
  • Part 2: Time to Response (TTR) [ Time Frame: From the date of the first dose of the study treatment to the date of the first documentation of response (up to 12 months) ]
    Time from the date of the first dose of the study treatment to the date of the first documentation of response (PR or better). PR is >=50% reduction of serum M protein and reduction in 24-hour urinary M protein by >=90% or to <200 mg/24 hour. If serum and urine M protein are not measurable, >=50% decrease in difference between involved and uninvolved FLC levels is required in place of M protein criteria. If serum and urine M protein and serum FLC assay are not measurable, >=50% reduction in bone marrow plasma cells is required in place of M protein, provided baseline percentage was >=30%. In addition, if present at baseline, >=50% reduction in size of soft tissue plasma cytomas is required. Two consecutive assessments are needed; no known evidence of progressive or new bone lesions if radiographic studies were performed.
  • Part 2: Percentage of Participants Who Achieved Complete Response (CR) or Very Good Partial Response (VGPR) [ Time Frame: Up to 12 months ]
    CR or VGPR is defined by IMWG criteria. CR is defined as Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow; in participants for whom only measurable disease is by serum FLC level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria is required; Two consecutive assessments are needed. VGPR is defined as serum and urine M component detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M component plus urine M component <100 mg/24 h; in participants for whom only measurable disease is by serum FLC level, >90% decrease in difference between involved and uninvolved FLC levels, in addition to VGPR criteria, is required; Two consecutive assessments are needed.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of TAK-169 in Participants With Relapsed or Refractory Multiple Myeloma
Official Title  ICMJE A Phase 1, Open-Label, Dose-Escalation, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TAK-169 in Patients With Relapsed or Refractory Multiple Myeloma
Brief Summary

Multiple Myeloma is a type of blood cancer in cells made in the bone marrow. Relapsed means the previous cancer treatment worked for a while but stopped working, over time. Refractory means people did not respond to previous cancer treatment. TAK-169 is a medicine that binds to the surface of multiple myeloma cells called CD38 cells. It delivers a dose of chemotherapy to the CD38 cells.

This study is in 2 parts.

The main aims of Part 1 of the study are to check how much TAK-169 a person can receive without getting side effects from it, and to work out the best dose of TAK-169 to give people to treat their cancer. The main aim of Part 2 of the study is to learn if the condition of people with multiple myeloma improves after treatment with TAK-169. Another aim is to check for side effects from TAK-169.

In Part 1, at the first visit, the study doctor will check who can take part. Participants who can take part will receive TAK-169 slowly through the vein (infusion). This will happen once a week during a 28-day cycle. Different small groups of participants will receive lower to higher doses of TAK-169. The study doctors will check for side effects after each dose of TAK 169. In this way, researchers can work out the best dose of TAK-169 to give participants in Part 2 of the study. Each participant will stay in the clinic for at least 24 hours after they have received their first infusion of TAK-169.

Once the best dose has been worked out, different small groups of participants will receive lower to higher doses of TAK-169 every 2 weeks, starting at the best dose.

In Part 2, at the first visit, the study doctor will check who can take part, as only some participants with multiple myeloma can take part.

Participants who previously did not respond to daratumumab or it worked for a while but stopped working, over time will have 1 of 2 treatments.

  • Some will receive TAK-169 once a week.
  • Others will receive TAK-169 every 2 weeks.

Participants who have never previously received other medicines that bind to the multiple myeloma CD38 cells can also take part. They will receive TAK-169 once a week.

All participants in Part 2 will receive the best dose of TAK-169 worked out in Part 1.

In both parts of the study, participants can receive TAK-169 for up to 1 year. They could receive TAK-169 for longer than 1 year if their multiple myeloma continues to improve or remains stable during treatment. After treatment has finished, participants will visit the clinic for a check-up every 12 weeks.

Detailed Description

The drug being tested in this study is called TAK-169. The study will evaluate the safety, tolerability, preliminary efficacy, PK, pharmacodynamics, and immunogenicity of TAK-169 monotherapy in participants with RRMM.

The study will be conducted in 2 phases: Dose Escalation Phase (Part 1) and an Expansion Phase (Part 2). The study will enroll approximately 81 to 102 participants (39 to 60 participants in Part 1 and approximately 54 participants in Part 2).

In the Dose Escalation Phase (Part 1), the starting dose level will be 50 microgram/kilogram (mcg/kg), once weekly. On the basis of investigator and sponsor review of available safety, PK, pharmacodynamic, and efficacy data from Cohort 1, the dose will be escalated in the subsequent cohorts to 100, 200, 335, 500, and 665 mcg/kg, once weekly. A separate dose escalation may also occur in which TAK-169 will be administered once every 2 weeks.

In the Expansion Phase (Part 2), the study will evaluate two types of RRMM cohorts: Daratumumab-relapsed or Refractory (RR) Cohorts (once weekly and once every 2 weeks TAK-169 administration) and an Anti-CD38 Therapy Naive Cohort (once weekly TAK-169 administration). The starting dose for each expansion cohort will be the MTD/RP2D (once weekly and once every 2 weeks) determined in Part 1 after review of the available safety, efficacy, PK, and pharmacodynamic data from the dose escalation phase of the study.

This multi-center trial will be conducted in the United States. The overall duration of the study is 34 months. Participants will be followed up for 30 days after the last dose of study drug for a follow-up assessment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Relapsed and/or Refractory Multiple Myeloma
Intervention  ICMJE Drug: TAK-169
TAK-169 intravenous infusion.
Study Arms  ICMJE
  • Experimental: Part 1: TAK-169 50 mcg/kg Once Weekly
    TAK-169 50 microgram per kilogram (mcg/kg), infusion, intravenously, once weekly on Days 1, 8, 15, and 22 in a 28-day treatment cycle until progressive disease (PD), unacceptable toxicity or withdraw from the study for other reasons.
    Intervention: Drug: TAK-169
  • Experimental: Part 1: TAK-169 100 mcg/kg Once Weekly
    TAK-169 100 mcg/kg, infusion, intravenously, once weekly on Days 1, 8, 15, and 22 in a 28-day treatment cycle until PD, unacceptable toxicity or withdraw from the study for other reasons.
    Intervention: Drug: TAK-169
  • Experimental: Part 1: TAK-169 200 mcg/kg Once Weekly
    TAK-169 200 mcg/kg, infusion, intravenously, once weekly on Days 1, 8, 15, and 22 in a 28-day treatment cycle until PD, unacceptable toxicity or withdraw from the study for other reasons.
    Intervention: Drug: TAK-169
  • Experimental: Part 1: TAK-169 335 mcg/kg Once Weekly
    TAK-169 335 mcg/kg, infusion, intravenously, once weekly on Days 1, 8, 15, and 22 in a 28-day treatment cycle until PD, unacceptable toxicity or withdraw from the study for other reasons.
    Intervention: Drug: TAK-169
  • Experimental: Part 1: TAK-169 500 mcg/kg Once Weekly
    TAK-169 500 mcg/kg, infusion, intravenously, once weekly on Days 1, 8, 15, and 22 in a 28-day treatment cycle until PD, unacceptable toxicity or withdraw from the study for other reasons.
    Intervention: Drug: TAK-169
  • Experimental: Part 1: TAK-169 665 mcg/kg Once Weekly
    TAK-169 665 mcg/kg, infusion, intravenously, once weekly on Days 1, 8, 15, and 22 in a 28-day treatment cycle until PD, unacceptable toxicity or withdraw from the study for other reasons.
    Intervention: Drug: TAK-169
  • Experimental: Part 1: TAK-169 TBD Once Every Two Weeks
    TAK-169 TBD, infusion, intravenously, once every 2 weeks on Days 1 and 15 in a 28-day treatment cycle until PD, unacceptable toxicity or withdraw from the study for other reasons. Dose escalation of TAK-169 will be based on the investigator and sponsor review of available safety, PK, pharmacodynamics, efficacy data in the previous cohort.
    Intervention: Drug: TAK-169
  • Experimental: Part 2, Daratumumab RR: TAK-169 TBD Once Weekly
    TAK-169 TBD, infusion, intravenously, once weekly in participants who are relapsed or refractory (RR) to daratumumab until PD, unacceptable toxicity or withdraw from the study for other reasons. Dose for Part 2 will be determined based on the review of the available safety, efficacy, PK, and pharmacodynamics data from Part 1 of this study.
    Intervention: Drug: TAK-169
  • Experimental: Part 2, Daratumumab RR: TAK-169 TBD Once Every Two Weeks
    TAK-169 TBD, infusion, intravenously, once every 2 weeks in participants who are RR to daratumumab until PD, unacceptable toxicity or withdraw from the study for other reasons. Dose for Part 2 will be determined based on the review of the available safety, efficacy, PK, and pharmacodynamics data from Part 1 of this study.
    Intervention: Drug: TAK-169
  • Experimental: Part 2, Anti-CD38 Therapy Naive MM: TAK-169 TBD Once Weekly
    TAK-169 TBD, infusion, intravenously, once weekly in participants with MM who have never received anti-CD38 therapy until PD, unacceptable toxicity or withdraw from the study for other reasons. Dose for Part 2 will be determined based on the review of the available safety, efficacy, PK, and pharmacodynamics data from Part 1 of this study.
    Intervention: Drug: TAK-169
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 10, 2019)
102
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 17, 2023
Estimated Primary Completion Date January 17, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Inclusion Criteria Part 1

  1. With a confirmed diagnosis of MM.
  2. With RRMM who have failed treatment with, are intolerant to, or are not candidates for available therapies that are known to confer clinical benefit in this participant population.
  3. Must meet all of the following criteria for prior therapy:

    • Must be refractory to at least one proteasome inhibitor (PI), at least one immunomodulatory drug (IMiD), and at least 1 steroid.
    • Must either have received >=3 prior lines of therapy or must have received at least two prior lines of therapy if one of those lines included a combination of PI and IMiD.
    • Prior treatment with an anti-CD38 therapy (including daratumumab) is permitted.
  4. With measurable disease, defined as at least 1 of the following:

    • Serum M-protein >=500 mg/dL (>=5 g/L) on serum protein electrophoresis (SPEP).
    • Urine M-protein >=200 mg/24 h on urine protein electrophoresis (UPEP).
    • Serum FLC assay result with an involved FLC level >=10 mg/dL (>=100 milligram per liter [mg/L]), provided the serum FLC ratio is abnormal.
  5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  6. With normal QT interval corrected by the Fridericia method (QTcF) on screening electrocardiogram (ECG), defined as QTcF of <=450 millisecond (ms) in males or <=470 ms in females
  7. Must meet the following clinical laboratory criteria at study entry:

    • Total bilirubin <=1.5*the upper limit of the normal range (ULN), except for participant with Gilbert's syndrome, in whom the direct bilirubin must be <2.0*ULN.
    • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be <=2.5*ULN.
    • Estimated glomerular filtration rate (eGFR) >=30 milliliters per minute (mL/min/1.73 square meter [m^2], using the modification of diet in renal disease (MDRD) equation.
    • Absolute neutrophil count (ANC) >=1000 per cubic millimeter (/mm^3) (>=1.0*10^ 9 per liter [/L]); a count of >=750/mm^3 (>=0.75*10^ 9/L) may be acceptable for participants with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Platelet count >=75,000/ mm^3 (>=75*10^ 9/L); a value of >=50,000/ mm^3 (>=50*10^ 9/L) may be acceptable for participants with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Hemoglobin >=7.5 g/dL (it is not permissible to transfuse a participant to reach this level).

Inclusion Criteria Part 2

  1. With a confirmed diagnosis of MM.
  2. Must meet all of the following criteria for prior therapy:

    • Must be refractory or intolerant to at least 1 PI and at least 1 IMiD.
    • Must either have received >=3 prior lines of therapy or must have received at least 2 prior lines of therapy if 1 of those lines included a combination of PI and IMiD.
    • Prior treatment with an anti-CD38 therapy (including daratumumab) is permitted, except for participants enrolled into the anti-CD38-therapy naïve expansion cohort.
    • Daratumumab-RR cohorts (once weekly and once every two weeks TAK-169 dosing): Participant must be RR to daratumumab at any time during treatment. Of note, participant's RR to other anti-CD38 therapies are excluded.
    • Anti-CD38 Therapy Naïve cohort (once weekly dosing): Participants must not have received any prior anti-CD38 therapy.
  3. With measurable disease, defined as at least 1 of the following:

    • Serum M-protein >=500 mg/dL (>=5 g/L) on SPEP.
    • Urine M-protein >=200 mg/24 hours on UPEP.
    • Serum FLC assay result with an involved FLC level >=10 mg/d (>=100 mg/L), provided the serum FLC ratio is abnormal
  4. ECOG performance status score of 0 or 1.
  5. With normal QTcF on screening ECG, defined as QTcF of <=450 ms in males or <=470 ms in females
  6. Must meet the following clinical laboratory criteria at study entry:

    • Total bilirubin <=1.5*the ULN, except for participant with Gilbert's syndrome, in whom the direct bilirubin must be <2.0*ULN.
    • Serum ALT and ASTmust be <=2.5*ULN.
    • eGFR >=30 mL/min/1.73 m^2, using the MDRD equation.
    • ANC >=1000 mm^3 (>=1.0*10^ 9 /L); a count of >=750/mm^3 (>=0.75*10^ 9/L) may be acceptable for participant with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Platelet count >=75,000/ mm^3 (>=75*10^ 9/L); a value of >=50,000/ mm^3 (>=50*10^ 9/L) may be acceptable for participants with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Hemoglobin >=7.5 g/dL (it is not permissible to transfuse a participant to reach this level).

Exclusion Criteria:

  1. With polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, or Immunoglobulin M (IgM) myeloma.
  2. With sensory or motor neuropathy of NCI CTCAE Grade >=3.
  3. Have received a final dose of any of the following treatments/procedures within the following minimum interval before the first dose of TAK-169:

    • Myeloma-specific therapy, including PIs and IMiDs-14 days
    • Anti-CD38 (a) therapy (Once the MTD/RP2D has been established, the washout period may be adjusted in the expansion phase (Part 2) of the study for participants who have received anti-CD38 therapy )-90 days
    • Corticosteroid therapy for myeloma- 7 days
    • Radiation therapy for localized bone lesions- 14 days
    • Major surgery-30 days
    • Autologous stem cell transplant- 90 days
    • Investigational therapy- 30 days
  4. Have received an allogeneic stem cell transplant or organ transplantation.
  5. Have not recovered, to NCI CTCAE V5 Grade <=1 or baseline, from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia.
  6. With clinical signs of central nervous system (CNS) involvement of MM.
  7. With known or suspected light chain amyloidosis of any organ (the presence of amyloid on the bone marrow biopsy without other evidence of amyloidosis is acceptable).
  8. With congestive heart failure (New York Heart Association) class >=II or left ventricular ejection fraction (LVEF <40%, cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris or myocardial infarction within the past 6 months, clinically significant arrhythmia requiring therapy including anticoagulants, or clinically significant uncontrolled hypertension. Participants are also excluded if cardiac MRI demonstrates evidence of infiltrative disease of the myocardium, such as amyloid cardiomyopathy.
  9. With chronic or active infection requiring systemic therapy, as well as a history of symptomatic viral infection that has not been fully cured (example, human immunodeficiency viruses (HIV) or viral hepatitis B or C).
  10. With a history of systemic inflammatory response syndrome (SIRS)/ cytokine release syndrome (CRS) reactions following infusion with any monoclonal antibodies or Chimeric Antigen Receptor (CAR) T-cell therapy
  11. With a chronic condition requiring the use of systemic corticosteroids at a dose of >10 milligram per day (mg/day) of prednisone or equivalent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Takeda Study Registration Call Center +1-877-825-3327 MedinfoUS@takeda.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04017130
Other Study ID Numbers  ICMJE TAK-169-1001
U1111-1224-6002 ( Other Identifier: WHO )
2019-000931-24 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: 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/
Responsible Party Takeda
Study Sponsor  ICMJE Takeda
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Takeda
PRS Account Takeda
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP