Clinical Trial: NCT03215030 - My Cancer Genome

NCT03215030

Description:

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.

Related Conditions:

Multiple Myeloma
Plasmacytoma

Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT03215030

Trial Eligibility

Document

Title

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

Clinical Trial IDs

ORG STUDY ID: TAK-573-1501
SECONDARY ID: TV48573-ONC-10128
SECONDARY ID: U1111-1195-8134
NCT ID: NCT03215030

Conditions

Multiple Myeloma

Interventions

Drug	Synonyms	Arms
TAK-573	TEV-48573	Phase 1 Schedule A: TAK-573 0.001 to 14 mg/kg
Dexamethasone		Phase 2: TAK-573 TBD

Purpose

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.

      The Phase 2 will further assess the safety profile of TAK-573 and its efficacy at MTD or OBD.

      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.

Trial Arms

Name	Type	Description	Interventions
Phase 1 Schedule A: TAK-573 0.001 to 14 mg/kg	Experimental	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.	TAK-573
Phase 1 Schedule B: TAK-573 TBD	Experimental	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.	TAK-573
Phase 1 Schedule C: TAK-573 TBD	Experimental	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.	TAK-573
Phase 1 Schedule D: TAK-573 TBD	Experimental	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.	TAK-573
Phase 2: TAK-573 TBD	Experimental	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.	TAK-573 Dexamethasone

Eligibility 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.

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	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
Safety Issue:
Description:	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).

Secondary Outcome Measures

Measure:	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)
Safety Issue:
Description:	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).

Measure:	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)
Safety Issue:
Description:	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).

Measure:	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)
Safety Issue:
Description:	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).

Measure:	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)
Safety Issue:
Description:	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).

Measure:	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)
Safety Issue:
Description:	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).

Measure:	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)
Safety Issue:
Description:	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).

Measure:	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)
Safety Issue:
Description:	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).

Measure:	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)
Safety Issue:
Description:	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).

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

Measure:	Phase 1- Clinical Benefit Rate (CBR)
Time Frame:	Up to 1 year
Safety Issue:
Description:	The CBR is defined as the percentage of participants who achieved an ORR along with the MR or better during the study as assessed with IMWG Uniform Response Criteria. ORR is defined as the percentage of participants who achieved confirmed PR or better during the study. 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%. 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).

Measure:	Phase 1- Disease Control Rate (DCR)
Time Frame:	Up to 1 year
Safety Issue:
Description:	The DCR is defined as the percentage of participants who achieved CBR along with a stable disease (SD) or better during the stud. The CBR is defined as the percentage of participants who achieved an ORR along with the minimal response (MR) or better during the study as assessed with IMWG Uniform Response Criteria. SD is defined as not meeting the response criteria for CR (any variant), VGPR, PR, MR, or PD and no known evidence of progressive or new bone lesions if radiographic studies were performed.

Measure:	Phase 1- DOR
Time Frame:	Up to 1 year
Safety Issue:
Description:	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.

Measure:	Phase 1- PFS
Time Frame:	Up to 1 year
Safety Issue:
Description:	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.

Measure:	Phase 1- Time to Response
Time Frame:	Up to 1 year
Safety Issue:
Description:	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.

Measure:	Percentage of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (nAb)
Time Frame:	Up to 1 year
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:	TEAEs and DLT-like will be evaluated as per NCI CTCAE, version 4.03.

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Millennium Pharmaceuticals, Inc.

Trial Keywords

Drug Therapy

Last Updated

December 21, 2020

Clinical Trials /

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