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

Multiple Myeloma Clinical Trial

Official title:

A Phase 2, Open-Label Study of Ixazomib+Daratumumab+Dexamethasone (IDd) in Relapsed and/or Refractory Multiple Myeloma (RRMM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03439293
• Other study ID #: C16047
• Secondary ID: U1111-1202-60222
• Status: Completed
• Phase: Phase 2
• Start date: March 13, 2018
• Est. completion date: June 9, 2023

Study information

• Verified date: June 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 4 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: June 9, 2023
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Ixazomib
Ixazomib capsule.
• Daratumumab
Daratumumab IV infusion.
• Dexamethasone
Dexamethasone tablets.

Locations

Country	Name	City	State
Czechia	Fakultni Nemocnice Brno	Brno
Czechia	Fakultni Nemocnice Olomouc	Olomouc	Olomoucky
Czechia	Fakultni Nemocnice Ostrava	Ostrava - Poruba	Severomoravsky KRAJ
Czechia	Onkologicka klinika Vseobecna fakultni nemocnice v Praze a 1	Praha
Czechia	Fakultni Nemocnice Kralovske Vinohrady	Praha 10	Praha
France	Hopital Claude Huriez	Lille Cedex	NORD Pas-de-calais
France	Hopital Hotel Dieu	Nantes Cedex 1	PAYS DE LA Loire
France	Hopital Saint-Antoine	Paris	Ile-de-france
France	Centre Hospitalier Lyon Sud	Pierre Benite Cedex	Rhone-alpes
Greece	Alexandra General Hospital of Athens	Athens	Attica
Greece	Evaggelismos General Hospital	Athens	Attica
Greece	University General Hospital of Patras Panagia I Voithia	Patras	Peloponnese
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam	Noord-holland
Netherlands	Albert Schweitzer Ziekenhuis Dordwijk	Dordrecht	South Holland
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden	Friesland
Netherlands	Erasmus Medisch Centrum	Rotterdam	Zuid-holland
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Poland	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza	Brzozow	Podkarpackie
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich	Chorzow	Slaskie
Poland	Szpitale Pomorskie Spolka z ograniczona odpowiedzialnoscia	Gdynia	Pomorskie
Poland	Szpital Uniwersytecki w Krakowie	Krakow	Malopolskie
Poland	Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lodz	Lodzkie
United States	Pacific Cancer Medical Center	Anaheim	California
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Research Medical Center - Kansas City	Kansas City	Missouri
United States	SCRI - Tennessee Oncology - Nashville - Centennial	Nashville	Tennessee
United States	SCRI - Florida Cancer Specialists - Panhandle	Tallahassee	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Czechia,  France,  Greece,  Netherlands,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 data cut-off: 1 January 2022 (Approximately 4 years)
Secondary	Progression-free Survival (PFS)	PFS is defined as time from date of first dose of drug to date of first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Participant without documentation of PD or death were censored at the date of last response assessment that is stable disease (SD) or better. PD is defined as increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase =0.5 g/dl); or urine M-component (absolute increase =200 mg/24-hour); difference between involved and uninvolved FLC levels (absolute increase >10 mg/dl); or bone marrow plasma cell percentage (absolute plasma cell percentage =10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder. SD is defined as not meeting criteria for other responses.	Up to data cut-off: 1 January 2022 (Approximately 4 years)
Secondary	Time to Progression (TTP)	TTP is defined as the time from the first dose of any study drug treatment to the date of the first documented PD. PD is defined as increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase =0.5 g/dl); or urine M-component (absolute increase =200 mg/24-hour); difference between involved and uninvolved FLC levels (absolute increase >10 mg/dl); or bone marrow plasma cell percentage (absolute plasma cell percentage =10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.	Up to data cut-off: 1 January 2022 (Approximately 4 years)
Secondary	Overall Survival (OS)	OS is defined as the time from the date of first dose of any study drug treatment to the date of death. Participant without documentation of death at the time of analysis will be censored at the last visit at which s/he was known to be alive.	Up to data cut-off: 1 January 2022 (Approximately 4 years)
Secondary	Overall Response Rate (ORR)	ORR is defined as percentage of participants with complete response (CR), VGPR and partial response (PR). CR: Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow; normal free light chain (FLC) ratio of 0.26-1.65; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein + urine M-protein level <100 mg/24 hours; and PR: >=50% reduction of serum M protein and reduction in 24-hour urinary M protein by >=90%/to <200 mg/24 hours; In addition, if present at baseline, >=50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions. The percentage of participants were rounded off to the single decimal point.	Up to data cut-off: 1 January 2022 (Approximately 4 years)
Secondary	Time To Response (TTR)	TTR is defined as the time from first dose of any study drug treatment to the date of first documentation of PR or better. PR is defined as >=50% reduction of serum M protein and reduction in 24-hour urinary M protein by >=90%/to <200 mg/24 hours; In addition, if present at baseline, >=50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions.	Up to data cut-off: 1 January 2022 (Approximately 4 years)
Secondary	Duration of Response (DOR)	DOR is defined as the time from the date of first documentation of PR or better to the date of the first documented PD among participants who responded to the treatment.	Up to data cut-off: 1 January 2022 (Up to approximately 4 years)