A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma

NCT05183139 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: C16063
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main aim is to show that long-term use of ixazomib can improve symptoms of multiple myeloma and provide an effective long-term alternative treatment. Participants will take ixazomib orally (by mouth) with pomalidomide and dexamethasone or lenalidomide and dexamethasone in 28-day treatment cycles. Participants will be treated for a maximum of 39 cycles but may continue to receive ixazomib beyond 39 cycles if they are benefiting from it. A follow-up study visit will occur 30 days after the last dose of ixazomib. Participants will be monitored for up to 3 years.

Conditions

Multiple Myeloma

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is defined as the time from the date of the first administration of the study drug regimen ixazomib with pomalidomide and dexamethasone or ixazomib with lenalidomide and dexamethasone (IPd/IRd) to the date of the first documentation of disease progression before the start of next line of therapy based on local laboratory results and the investigator's assessment using modified International Myeloma Working Group (IMWG) response criteria or death due to any cause, whichever occurs first.

  Up to approximately 5 years

Secondary Outcomes (8)

• Percentage of Participants Maintaining or Achieving PR, Very Good Partial Response (VGPR), or Complete Response (CR)

  Up to approximately 5 years

• Time to Progression (TTP)

  Up to approximately 5 years

• Duration of Therapy (DoT 1)

  Up to approximately 5 years

• Duration of Therapy (DoT 2)

  Up to approximately 5 years

• Duration of PI Therapy

  Up to approximately 5 years

Study Arms (2)

Cohort A: Ixazomib 4 mg + Pomalidomide 4 mg + Dexamethasone 40 mg

EXPERIMENTAL

Ixazomib 4 mg (3 mg for participants with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis), capsules, orally, on Days 1, 8, and 15, along with pomalidomide 4 mg, capsules, orally from Days 1 to 21 and dexamethasone 40 mg (20 mg if the participant is over 75 years of age), tablets, orally on Days 1, 8, 15, and 22 of each 28-day cycle, for a maximum of 39 cycles or until disease progression or unacceptable toxicity leading to discontinuation of ixazomib or to a change in regimen. Participants who were taking modified doses of pomalidomide or dexamethasone can start at that dose level in the study.

Drug: Ixazomib; Drug: Pomalidomide; Drug: Dexamethasone

Cohort B: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg

EXPERIMENTAL

Ixazomib 4 mg (3 mg for participants with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis), capsules, orally, on Days 1, 8, and 15, along with lenalidomide 25 mg capsules, orally, from Days 1 to 21 and dexamethasone 40 mg (20 mg if the participant is over 75 years of age), tablets, orally, on Days 1, 8, 15, and 22 of each 28-day cycle, for a maximum of 39 cycles or until disease progression or unacceptable toxicity leading to discontinuation of ixazomib or to a change in regimen. Participants who were taking modified doses of lenalidomide or dexamethasone can start at that dose level in the study.

Drug: Ixazomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

Ixazomib capsules

Also known as: NINLARO

Cohort A: Ixazomib 4 mg + Pomalidomide 4 mg + Dexamethasone 40 mg; Cohort B: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg

Pomalidomide DRUG

Pomalidomide capsules

Also known as: POMALYST

Cohort A: Ixazomib 4 mg + Pomalidomide 4 mg + Dexamethasone 40 mg

Lenalidomide DRUG

Lenalidomide capsules

Also known as: REVLIMID

Cohort B: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg

Dexamethasone DRUG

Dexamethasone tablets

Cohort A: Ixazomib 4 mg + Pomalidomide 4 mg + Dexamethasone 40 mg; Cohort B: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a diagnosis of multiple myeloma (MM) using current IMWG diagnostic criteria, and are relapsed or refractory to 1 to 3 prior lines of therapy\*.
• a. Has completed 3 or 4 cycles of a parenteral proteasome inhibitor (PI), and lenalidomide- or pomalidomide-based regimen and achieved a response of ≥ partial response (PR) with no evidence of disease progression as defined by IMWG criteria. This lead-in therapy to in-class transition (iCT) is not included as part of the 1 to 3 prior lines and should be completed no more than 28 days prior to initiation of IRd or IPd in this study.
• Those with light chain myeloma and free light chain (FLC) only may be enrolled if they previously met or currently meet the criteria for a diagnosis of MM.
• \*A line of therapy is defined as one or more cycles of a planned treatment program. This may consist of one or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem-cell transplantation, followed by maintenance is considered one line of therapy. Autologous and allogenic transplants are permitted.
• Has a diagnosis of non-secretory disease as long as the participant has a marker of disease that can be followed serially and assessed for response.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status of 0, 1, or 2 at the time of enrollment.

You may not qualify if:

• Has Grade \>2 peripheral neuropathy (PN), or Grade 2 PN with pain on clinical examination.
• Has not adequately recovered from other non-neuropathy AEs related to prior therapy in the opinion of the investigator at the time of enrollment.
• Is pomalidomide refractory.
• Has primary light chain amyloidosis (AL). Those with MM and concurrent AL are allowed.
• Has known central nervous system involvement by MM.
• Has infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment.
• Has ongoing or active systemic infection, active hepatitis B or C virus infection, or known positive status for human immunodeficiency virus.
• Has been diagnosed or treated for another malignancy within 2 years before enrollment or has previously been diagnosed with another malignancy and has any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Has previously been treated with ixazomib or participated in a study with ixazomib whether treated with ixazomib or not.

Sponsors & Collaborators

• Takeda: lead

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; pomalidomide; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: January 10, 2022
• Study Start: June 30, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 3, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.