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

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ClinicalTrials.gov Identifier: NCT03439293
Recruitment Status : Recruiting
First Posted : February 20, 2018
Last Update Posted : September 7, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of ixazomib in combination with daratumumab and dexamethasone in participants with relapsed and/or refractory myeloma.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Ixazomib Drug: Daratumumab Drug: Dexamethasone Phase 2

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 Ixazomib + Daratumumab + Dexamethasone (IDd) in people who have relapsed and/or refractory multiple myeloma (RRMM).

The study will enroll approximately 60 patients. 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 worldwide. The overall time to participate in this study is 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label Study of Ixazomib+Daratumumab+Dexamethasone (IDd) in Relapsed and/or Refractory Multiple Myeloma (RRMM)
Actual Study Start Date : June 8, 2018
Estimated Primary Completion Date : December 2, 2019
Estimated Study Completion Date : December 31, 2023


Arm Intervention/treatment
Experimental: 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), have an unacceptable toxicity, or withdraw consent, or when the study has completed or until the sponsor terminates the study.
Drug: Ixazomib
Ixazomib capsule
Other Name: NINLARO

Drug: Daratumumab
Daratumumab IV infusion

Drug: Dexamethasone
Dexamethasone tablets




Primary Outcome Measures :
  1. Percentage of Participants With Very Good Partial Response (VGPR) or Better [ Time Frame: Up to 3 years ]
    Response will be 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 mg per 24 hours.


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Up to 5 years ]
    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. PD: Increase of 25% from lowest response value in any of following: Serum M component with increase ≥ 0.5 gm/dL; serum M component increases ≥1 gm/dL are sufficient to define relapse if starting M component is ≥ 5 gm/dL and/or; Urine M component (absolute increase must be ≥ 200 mg/24 h) and/or, development of new/definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia that can be attributed to plasma cell proliferative disorder.

  2. Time to Progression (TTP) [ Time Frame: Up to 5 years ]
    TTP is defined as the time from the first dose of any study drug treatment to the date of the first documented progressive disease (PD). PD: Increase of 25% from lowest response value in any of following: Serum M component with increase ≥ 0.5 gm/dL; serum M component increases ≥1 gm/dL are sufficient to define relapse if starting M component is ≥ 5 gm/dL and/or; Urine M component (absolute increase must be ≥ 200 mg/24 h) and/or, development of new/definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia that can be attributed to plasma cell proliferative disorder.

  3. Overall Survival (OS) [ Time Frame: Up to 5 years ]
    OS is defined as the time from the date of first dose of any study drug treatment to the date of death.

  4. Overall Response Rate (ORR) [ Time Frame: Up to 5 years ]
    ORR is defined as 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 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 h; In addition, if present at baseline, ≥50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions.

  5. Time To Response (TTR) [ Time Frame: Up to 5 years ]
    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 h; In addition, if present at baseline, ≥50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions.

  6. Duration of Response (DOR) [ Time Frame: Up to 5 years ]
    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. PR is defined as ≥50% reduction of serum M protein and reduction in 24-hour urinary M protein by ≥90%/to <200 mg/24 h; In addition if present at baseline, ≥50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

    • serum M-protein ≥1 gm/dL (≥10 gm/L).
    • urine M-protein ≥200 mg/24 hours.
  2. Have documented evidence of progressive disease (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 [eg, 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/mm3.
    • Platelet count ≥75,000/mm3.
    • Total bilirubin ≤1.5 x the upper limit of the normal range (ULN) (except for Gilbert syndrome: direct bilirubin ≤2 x ULN).
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x 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 participants 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 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, known human immunodeficiency virus (HIV-RNA) positive, known hepatitis B surface antigen seropositive, or known hepatitis C virus-RNA positive. Note: Participants who have positive hepatitis B core antibody can be enrolled but must have hepatitis B virus-DNA negative. Participants who have positive hepatitis C antibody can be enrolled but must have hepatitis C virus-RNA negative.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03439293


Contacts
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Contact: Takeda Study Registration Call Center +1-866-835-2233 globaloncologymedinfo@takeda.com

Locations
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United States, California
Pacific Cancer Medical Center Recruiting
Anaheim, California, United States, 92801
United States, Colorado
Colorado Blood Cancer Institute Not yet recruiting
Denver, Colorado, United States, 80218-1230
United States, Florida
SCRI - Florida Cancer Specialists - Panhandle Not yet recruiting
Tallahassee, Florida, United States, 32308
United States, Missouri
Research Medical Center - Kansas City Not yet recruiting
Kansas City, Missouri, United States, 64132
United States, Tennessee
SCRI - Tennessee Oncology - Nashville - Centennial Not yet recruiting
Nashville, Tennessee, United States, 58014
United States, Texas
The University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030-4017
Czechia
Fakultni Nemocnice Olomouc Not yet recruiting
Olomouc, Olomoucky, Czechia, 77900
Fakultni Nemocnice Kralovske Vinohrady Not yet recruiting
Praha 10, Praha, Czechia, 100 34
Fakultni Nemocnice Ostrava Not yet recruiting
Ostrava - Poruba, Severomoravsky KRAJ, Czechia, 708 52
Fakultni Nemocnice Brno Not yet recruiting
Brno, Czechia, 625 00
Onkologicka klinika Vseobecna fakultni nemocnice v Praze a 1 Not yet recruiting
Praha, Czechia, 128 08
France
Hopital Saint-Antoine Not yet recruiting
Paris, Ile-de-france, France, 75012
Hopital Claude Huriez Not yet recruiting
Lille Cedex, NORD Pas-de-calais, France, 59037
Hopital Hotel Dieu Not yet recruiting
Nantes Cedex 1, PAYS DE LA Loire, France, 44093
Centre Hospitalier Lyon Sud Not yet recruiting
Pierre Benite Cedex, Rhone-alpes, France, 69495
Greece
Evaggelismos General Hospital Not yet recruiting
Athens, Attica, Greece, 10676
Alexandra General Hospital of Athens Not yet recruiting
Athens, Attica, Greece, 11528
University General Hospital of Patras Panagia I Voithia Not yet recruiting
Patras, Peloponnese, Greece, 26504
Netherlands
Medisch Centrum Leeuwarden Not yet recruiting
Leeuwarden, Friesland, Netherlands, 8934 AD
Vrije Universiteit Medisch Centrum Not yet recruiting
Amsterdam, Noord-holland, Netherlands, 1081 HV
Albert Schweitzer Ziekenhuis Dordwijk Not yet recruiting
Dordrecht, South Holland, Netherlands, 3300 AK
Erasmus Medisch Centrum Not yet recruiting
Rotterdam, Zuid-holland, Netherlands, 3015 CE
Universitair Medisch Centrum Utrecht Not yet recruiting
Utrecht, Netherlands, 3584 CX
Poland
Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi Not yet recruiting
Lodz, Lodzkie, Poland, 93-510
Szpital Uniwersytecki w Krakowie Not yet recruiting
Krakow, Malopolskie, Poland, 31-501
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza Not yet recruiting
Brzozow, Podkarpackie, Poland, 36-200
Szpitale Pomorskie Spolka z ograniczona odpowiedzialnoscia Not yet recruiting
Gdynia, Pomorskie, Poland, 81-519
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich Not yet recruiting
Chorzow, Slaskie, Poland, 41-500
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Study Director Takeda

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03439293     History of Changes
Other Study ID Numbers: C16047
U1111-1202-6022 ( Other Identifier: WHO )
2017-003977-32 ( Registry Identifier: EudraCT )
First Posted: February 20, 2018    Key Record Dates
Last Update Posted: September 7, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Takeda:
Drug Therapy
Ixazomib
Daratumumab
Dexamethasone

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Ixazomib
Daratumumab
BB 1101
Glycine
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists