A Study of Ixazomib+Daratumumab+Dexamethasone (IDd) in Relapsed and/or Refractory Multiple Myeloma (RRMM)

NCT ID: NCT03439293

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-13
• Study Completion Date: 2023-06-26

Brief Summary

The purpose of this study is to evaluate the percentage of participants with a response of very good partial response (VGPR) or better to IDd treatment.

Detailed Description

The regimen being tested in this study is the combination of ixazomib, daratumumab, and dexamethasone. This study will look at the efficacy and safety of IDd in people who have RRMM.

The study will enroll approximately 60 Participants. Participants will be assigned to the treatment group:

• Ixazomib 4.0 mg + Daratumumab 16.0 mg/kg + Dexamethasone 20 mg

All participants will be asked to take Ixazomib on Days 1, 8 and 15 of each 28-day cycle plus Daratumumab on Days 1, 8, 15 and 22 of each 28-day cycle for Cycles 1 and 2, on Days 1 and 15 of each 28-day cycle for Cycles 3 through 6 and on Day 1 of each 28-day cycle for Cycle 7 and beyond plus Dexamethasone orally on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day cycle.

This multi-center trial will be conducted in the United States, Czech Republic, France, Poland, Greece and the Netherlands. The overall time to participate in this study is approximately 5 years. Participants will make multiple visits to the clinic, and every 12 weeks after PD until death or termination of the study by the sponsor.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ixazomib 4 mg + Daratumumab 16 mg/kg + Dexamethasone 20 mg

Ixazomib, 4 mg, capsules, orally, on Days 1, 8 and 15 of each 28-day cycle along with daratumumab, 16 mg/kg, intravenously (IV), on Days 1, 8, 15 and 22 of Cycles 1 and 2, on Days 1 and 15 (every 2 weeks) for Cycles 3 to 6 and on Day 1 (every 4 weeks) for Cycle 7 and beyond along with dexamethasone, 20 mg, tablets, orally on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day cycle until progressive disease (PD), unacceptable toxicity, or withdrawal of consent, or up to 5 years.

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsule.

Daratumumab

Intervention Type: DRUG

Daratumumab IV infusion.

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets.

Interventions

Ixazomib

Ixazomib capsule.

Intervention Type: DRUG

Daratumumab

Daratumumab IV infusion.

Intervention Type: DRUG

Dexamethasone

Dexamethasone tablets.

Intervention Type: DRUG

Other Intervention Names

NINLARO

Eligibility Criteria

Inclusion Criteria

1. Have measurable disease by at least 1 of the following measurements:

• serum M-protein >=1 gram per liter (g/dL) (>=10 g/L).
• urine M-protein >=200 mg/24 hours.

2. Have documented evidence of PD on or after their last regimen as defined by IMWG criteria. All participants must have received between 1 to 3 prior therapies for MM (a prior therapy is defined as 2 or more cycles of therapy given as a treatment plan for MM [example, a single-agent or combination therapy or a sequence of planned treatments such as induction therapy followed by autologous stem cell transplant (SCT) and then consolidation and/or maintenance therapy]).

3. Have achieved a response (partial response (PR) or better) to at least 1 prior therapy.

4. Have an Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.

5. Must meet the following laboratory criteria:

• Absolute neutrophil count (ANC) >=1000 per cubic millimeter (/mm^3).
• Platelet count >=75,000/mm^3.
• Total bilirubin less than or equal to (<=) 1.5*the upper limit of the normal range (ULN) (except for Gilbert syndrome: direct bilirubin <=2*ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3*ULN.
• Calculated creatinine clearance >=50 mL/min.

Exclusion Criteria

1. Have undergone prior allogenic bone marrow transplantation.

2. Have received prior ixazomib at any time or daratumumab or other anti-CD38 therapies, except as part of initial therapy if this was stopped to move on to SCT and the participant did not progress on anti-CD38 treatment.

3. Are refractory to bortezomib or carfilzomib at the last exposure before this study (defined as participants having PD while receiving bortezomib or carfilzomib therapy or within 60 days after ending bortezomib or carfilzomib therapy).

4. Are planning to undergo SCT prior to PD on this study (ie, these participants should not be enrolled in order to reduce disease burden prior to transplant).

5. Are receiving systemic treatment with strong Cytochrome P450 3A4 (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, St. John's wort) within 14 days before randomization.

6. Has received autologous SCT within 12 weeks before the date of study treatment.

7. With known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note: FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is <50% of predicted normal.

• Participants with Grade 2 or higher residual toxicities from prior therapy (including Grade 2 or higher peripheral neuropathy or any grade neuropathy with pain; excluding alopecia). This includes recovery from any major surgery. Note: Participants with planned surgical to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery.

8. Has uncontrolled clinically significant cardiac disease, including myocardial infarction within 6 months before date of study entry or unstable or uncontrolled angina, congestive heart failure, New York Heart Association (NYHA) Class III-IV, uncontrolled cardiac arrhythmia (Grade 2 or higher).

9. With ongoing or active systemic infection requiring intravenous IV medical management ; participants with known human immunodeficiency virus- Ribonucleic acid (HIV-RNA) positivity; participants with hepatitis B virus (HBV) surface antigen or core antibody positivity; and participants with known hepatitis C virus-RNA positivity. Note: Participants who have positive hepatitis B core antibody can be enrolled but must have hepatitis B virus- deoxyribonucleic acid (DNA) negative. Participants who have positive hepatitis C antibody can be enrolled but must have hepatitis C virus-RNA negativity.

Note: Participants who are already enrolled at the time of Amendment 02 should have local HBV testing performed as soon as possible for HBV surface antigen, e antigen, core antibody, and DNA. If any of these tests is positive, consult a physician with expertise in managing HBV for guidance regarding stopping daratumumab, starting HBV antiviral therapy, and remaining on study.

10. Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Pacific Cancer Medical Center

Anaheim, California, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

SCRI - Florida Cancer Specialists - Panhandle

Tallahassee, Florida, United States

Research Medical Center - Kansas City

Kansas City, Missouri, United States

SCRI - Tennessee Oncology - Nashville - Centennial

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Fakultni Nemocnice Olomouc

Olomouc, Olomoucký kraj, Czechia

Fakultni Nemocnice Kralovske Vinohrady

Prague, Prague, Czechia

Fakultni Nemocnice Ostrava

Ostrava - Poruba, Severomoravsky KRAJ, Czechia

Fakultni Nemocnice Brno

Brno, , Czechia

Onkologicka klinika Vseobecna fakultni nemocnice v Praze a 1

Prague, , Czechia

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Hopital Claude Huriez

Lille, Hauts-de-France, France

Hopital Hotel Dieu

Nantes, Pays de la Loire Region, France

Hopital Saint-Antoine

Paris, Île-de-France Region, France

Evaggelismos General Hospital

Athens, Attica, Greece

Alexandra General Hospital of Athens

Athens, Attica, Greece

University General Hospital of Patras Panagia I Voithia

Patras, Peloponnese, Greece

Vrije Universiteit Medisch Centrum

Amsterdam, North Holland, Netherlands

Medisch Centrum Leeuwarden

Leeuwarden, Provincie Friesland, Netherlands

Albert Schweitzer Ziekenhuis Dordwijk

Dordrecht, South Holland, Netherlands

Erasmus Medisch Centrum

Rotterdam, South Holland, Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Szpital Uniwersytecki w Krakowie

Krakow, Lesser Poland Voivodeship, Poland

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza

Brzozów, Podkarpackie Voivodeship, Poland

Szpitale Pomorskie Spolka z ograniczona odpowiedzialnoscia

Gdynia, Pomeranian Voivodeship, Poland

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich

Chorzów, Silesian Voivodeship, Poland

Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi

Lodz, Łódź Voivodeship, Poland

Countries

United States; Czechia; France; Greece; Netherlands; Poland

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1202-6022

Identifier Type: OTHER

Identifier Source: secondary_id

2017-003977-32

Identifier Type: REGISTRY

Identifier Source: secondary_id

C16047

Identifier Type: -

Identifier Source: org_study_id