Clinical trial NCT03439293: A Study of Ixazomib+Daratumumab+Dexamethasone (IDd) in Relapsed and/or Refractory Multiple Myeloma (RRMM)
Official title: A Phase 2, Open-Label Study of Ixazomib+Daratumumab+Dexamethasone (IDd) in Relapsed and/or Refractory Multiple Myeloma (RRMM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Drug Therapy
Ixazomib
Daratumumab
Dexamethasone
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-02-20
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants With Very Good Partial Response (VGPR) or Better (Complete Response + VGPR)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to 5 years
measure: Time to Progression (TTP)
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Overall Response Rate (ORR)
timeFrame: Up to 5 years
measure: Time To Response (TTR)
timeFrame: Up to 5 years
measure: Duration of Response (DOR)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Tallahassee
country: United States
facility: SCRI - Florida Cancer Specialists - Panhandle
state: Florida
city: Kansas City
country: United States
facility: Research Medical Center - Kansas City
state: Missouri
city: Nashville
country: United States
facility: SCRI - Tennessee Oncology - Nashville - Centennial
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc
state: Olomoucky
city: Praha 10
country: Czechia
facility: Fakultni Nemocnice Kralovske Vinohrady
state: Praha
city: Ostrava - Poruba
country: Czechia
facility: Fakultni Nemocnice Ostrava
state: Severomoravsky KRAJ
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno
city: Praha
country: Czechia
facility: Onkologicka klinika Vseobecna fakultni nemocnice v Praze a 1
city: Paris
country: France
facility: Hopital Saint-Antoine
state: Ile-de-france
city: Lille Cedex
country: France
facility: Hopital Claude Huriez
state: NORD Pas-de-calais
city: Nantes Cedex 1
country: France
facility: Hopital Hotel Dieu
state: PAYS DE LA Loire
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
state: Rhone-alpes
city: Athens
country: Greece
facility: Evaggelismos General Hospital
state: Attica
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens
state: Attica
city: Patras
country: Greece
facility: University General Hospital of Patras Panagia I Voithia
state: Peloponnese
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
state: Friesland
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
state: Noord-holland
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis Dordwijk
state: South Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
state: Zuid-holland
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Lodz
country: Poland
facility: Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
state: Lodzkie
city: Krakow
country: Poland
facility: Szpital Uniwersytecki w Krakowie
state: Malopolskie
city: Brzozow
country: Poland
facility: Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza
state: Podkarpackie
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Spolka z ograniczona odpowiedzialnoscia
state: Pomorskie
city: Chorzow
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
state: Slaskie
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: