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

Phase 2

Recruiting

• Conditions: blood cancer; Myeloma; 10035227

• Registration Number: NL-OMON48807
• Lead Sponsor: Takeda

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 1

Inclusion Criteria

Each patient must meet all of the following inclusion criteria to be enrolled
in the study:
• Adult patients (aged >=18 years) who have been diagnosed with MM according to
IMWG criteria.
• All patients must have measurable disease by at least 1 of the following
measurements:
- Serum M-protein >=1 g/dL (>=10 g/L).
- Urine M-protein >=200 mg/24 hours.
• All patients must have documented evidence of PD on or after their last
regimen as defined by IMWG criteria (see Appendix E) [1-3]. All patients 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 SCT and then consolidation and/or
maintenance therapy]).
• All patients must have achieved a response (PR or better) to at least 1 prior
therapy.
• All patients must have an Eastern Cooperative Oncology Group (ECOG) score of
0, 1, or 2.
• All patients 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.
• Female patients who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential, agree to use effective contraceptive
measures during and for 90 days following treatment. Advise women using
hormonal contraceptives to also use a barrier method of contraception (see
Appendix H for details).
• Male patients, even if surgically sterilized (ie, status postvasectomy), who:
- Agree to use effective contraceptive measures during and for 90 days
following treatment (see Appendix H for details).
• Voluntary written consent must be given before performance of any
study-related procedure not part of standard medical care, with the
understanding that consent may be withdrawn by the patient at any time without
prejudice to future medical care.
• Patient is willing and able to adhere to the study visit schedule and other
protocol requirements.

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not to be enrolled
in the study:
• Patients have undergone prior allogenic bone marrow transplantation.
• Patients 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 patient did not progress on anti-CD38 treatment.
• Patients are refractory to bortezomib or carfilzomib at the last exposure
before this study (defined as patient having PD while receiving bortezomib or
carfilzomib therapy or within 60 days after ending bortezomib or carfilzomib
therapy).
• Patients planning to undergo SCT prior to PD on this study (ie, these
patients should not be enrolled in order to reduce disease burden prior to
transplant).
• Patients receiving systemic treatment with strong CYP3A inducers (rifampin,
rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, St. John's
wort) within 14 days before randomization.
• Patient has received autologous SCT within 12 weeks before the date of study
treatment.
• Patient has received an investigational drug (including investigational
vaccines) within 4 weeks before study treatment (except for investigational
antimyeloma agents, which cannot be taken within 2 weeks prior or 5 PK
half-lives of the treatment, whichever is longer, before the date of study
treatment). The only exception is emergency use of a short course of
corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum 4 days)
before treatment.
• Patients 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 subjects suspected of having COPD and subjects
must be excluded if FEV1 is <50% of predicted normal.
- Patients 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:
Subjects with planned surgical procedures to be conducted under local
anesthesia may participate. Kyphoplasty or vertebroplasty are not considered
major surgery.
• Patients with known allergy to any of the study medications, their analogues,
their excipients, mAbs or human proteins or known sensitivity to
mammalian-derived products.
• Patient 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).
• Patients with ongoing or active systemic infection requiring IV medical
management; patients with known HIV-RNA positivity; patients with hepatitis B
virus (HBV) surface antigen or core antibody positivity,; and patients with
known hepatitis C virus-RNA positivity. Patients who have positive hepatitis C
antibody can be enrolled but must have hepatitis C virus-RNA negativity.
• Patient has any concurrent medical condition or disease that is likely to
interfere with study procedures, results, or assessment of safety or toxicity
or that in the opinion of the investigator would constitute a hazard for
participati

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint is response of VGPR or better as assessed by the<br /><br>investigator. Additionally efficacy will be assessed by PFS, TTP, ORR, TTR,<br /><br>DOR, and OS. Patients will be assessed for disease response by the investigator<br /><br>according to the IMWG criteria.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Safety assessments will be evaluated through the incidence and severity of<br /><br>adverse events (AEs) and changes in clinical hematology and chemistry<br /><br>laboratory test results.</p><br>