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

NCT03439293 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: C16047U1111-1202-60222017-003977-32
• Study Type: interventional
• Target: 61
• Locations: 6 countries
• Sites: 28

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.

Conditions

Multiple Myeloma

Keywords

Drug Therapy; Ixazomib; Daratumumab; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Very Good Partial Response (VGPR) or Better (Complete Response + VGPR)

  Response was assessed using International Myeloma Working Group (IMWG) Criteria. VGPR is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 milligram (mg) per 24 hours. The percentage of participants were rounded off to the single decimal point.

  Up to 5 years

Secondary Outcomes (6)

• Progression-free Survival (PFS)

  Up to 5 years

• Time to Progression (TTP)

  Up to 5 years

• Overall Survival (OS)

  Up to 5 years

• Overall Response Rate (ORR)

  Up to 5 years

• Time To Response (TTR)

  Up to 5 years

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: Ixazomib; Drug: Daratumumab; Drug: Dexamethasone

Interventions

Ixazomib DRUG

Ixazomib capsule.

Also known as: NINLARO

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

Daratumumab DRUG

Daratumumab IV infusion.

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

Dexamethasone DRUG

Dexamethasone tablets.

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

Eligibility Criteria

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

You may qualify if:

• 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.
• 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 \[example, a single-agent or combination therapy or a sequence of planned treatments such as induction therapy followed by autologous stem cell transplant (SCT) and then consolidation and/or maintenance therapy\]).
• Have achieved a response (partial response (PR) or better) to at least 1 prior therapy.
• Have an Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.
• 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.

You may not qualify if:

• Have undergone prior allogenic bone marrow transplantation.
• 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.
• 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).
• 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).
• 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.
• Has received autologous SCT within 12 weeks before the date of study treatment.
• 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.
• 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).
• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (28)

Pacific Cancer Medical Center

Anaheim, California, 92801, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

SCRI - Florida Cancer Specialists - Panhandle

Tallahassee, Florida, 32308, United States

Location

Research Medical Center - Kansas City

Kansas City, Missouri, 64132, United States

Location

SCRI - Tennessee Oncology - Nashville - Centennial

Nashville, Tennessee, 58014, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fakultni Nemocnice Olomouc

Olomouc, Olomoucký kraj, 77900, Czechia

Location

Fakultni Nemocnice Kralovske Vinohrady

Prague, Prague, 100 34, Czechia

Location

Fakultni Nemocnice Ostrava

Ostrava - Poruba, Severomoravsky KRAJ, 708 52, Czechia

Location

Fakultni Nemocnice Brno

Brno, 625 00, Czechia

Location

Onkologicka klinika Vseobecna fakultni nemocnice v Praze a 1

Prague, 128 08, Czechia

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France

Location

Hopital Claude Huriez

Lille, Hauts-de-France, 59037, France

Location

Hopital Hotel Dieu

Nantes, Pays de la Loire Region, 44093, France

Location

Hopital Saint-Antoine

Paris, Île-de-France Region, 75012, France

Location

Evaggelismos General Hospital

Athens, Attica, 10676, Greece

Location

Alexandra General Hospital of Athens

Athens, Attica, 11528, Greece

Location

University General Hospital of Patras Panagia I Voithia

Patras, Peloponnese, 26504, Greece

Location

Vrije Universiteit Medisch Centrum

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, Provincie Friesland, 8934 AD, Netherlands

Location

Albert Schweitzer Ziekenhuis Dordwijk

Dordrecht, South Holland, 3300 AK, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, South Holland, 3015 CE, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Szpital Uniwersytecki w Krakowie

Krakow, Lesser Poland Voivodeship, 31-501, Poland

Location

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

Brzozów, Podkarpackie Voivodeship, 36-200, Poland

Location

Szpitale Pomorskie Spolka z ograniczona odpowiedzialnoscia

Gdynia, Pomeranian Voivodeship, 81-519, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich

Chorzów, Silesian Voivodeship, 41-500, Poland

Location

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

Lodz, Łódź Voivodeship, 93-510, Poland

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; daratumumab; 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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: February 20, 2018
• Study Start: March 13, 2018
• Primary Completion: January 1, 2022
• Study Completion: June 26, 2023
• Last Updated: July 3, 2024
• Results First Posted: February 8, 2023

Record last verified: 2024-06

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.

Locations

PL (5); US (6); CZ (5); GR (3); FR (4); NL (5)