Ixazomib -Daratumumab Without Dexamethasone (IDara) in Elderly Relapse Refractory Multiple Myeloma

NCT03757221 | Terminated Phase 2 DMC

• 1 other identifier: 18-070
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple myeloma is an incurable hematological malignancy that affects older patients. Currently, despite recent progress, the disease relapses more or less quickly after initial treatment and requires the resumption of treatment with new drugs associated with cortisone, whose side effects are important. The investigators propose to conduct a phase 2 testing the combination ixazomib - daratumumab without dexamethasone.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Very Good Partial Response (VGPR) + Complete Response (CR) Rate using the IMWG response criteria

  The primary endpoint is the Very Good Partial Response (VGPR) + Complete Response (CR) Rate using the IMWG response criteria. Using IMWG criteria for best response reached at during the twelve months follow-up.

  12 months

Study Arms (1)

Combination ixazomib + daratumumab without dexamethasone

EXPERIMENTAL

Elderly Relapse Refractory Multiple Myeloma Patients treated by Combination ixazomib + daratumumab without dexamethasone

Combination Product: Ixazomib and Daratumumab

Interventions

Ixazomib and Daratumumab COMBINATION_PRODUCT

Daratumumab will be administrated every week for the first 2 cycles. For cycle 3 to 6, it will be administrated every two weeks at day 1 and day 15. From cycle 7 until progression Daratumumab will be administrated every 4 weeks. Ixazomib will be administrated every week three weeks on one week off at D1, D8 and D15 on a 28-d cycle basis. Dexamethasone will not be given except one series of 4 days of dexamethasone, 20 mg/day or a maximum of 80 mg, for emergencies and complications at initiation of treatment.

Combination ixazomib + daratumumab without dexamethasone

Eligibility Criteria

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

You may qualify if:

• Must be able to understand and voluntarily sign an informed consent form
• Must be able to adhere to the study visit schedule and other protocol requirements
• Age \>= 65 years
• Subjects affiliated with an appropriate social security system.
• Life expectancy \> 6 months
• Patients must have relapsed myeloma, and have been previously treated with Bortezomib, Melphalan and Prednisone (VMP) or Lenalidomide and Dexamethasone (Rd), or both:
• One or two line(s) of prior therapies
• Patients must have Progressive Disease as defined by the IMWG as one of the following (Kumar, 2016): Increase of 25% from lowest response value in any one or more of the following:
• Serum M-component (absolute increase must be ≥ 0.5 g/100 ml) and/or Urine M-component (absolute increase must be ≥ 200 mg per 24 h) and/or
• Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be \> 10 mg/l).
• Bone marrow plasma cell percentage (absolute % must be ≥ 10%)
• Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
• Development of hypercalcemia (corrected serum calcium \> 11.5 mg/100 ml) that can be attributed solely to the plasma cell proliferative disorder
• Patients must have undergone prior treatment with VMP or Rd:
• They must have received at least two cycles of therapy

You may not qualify if:

• Target disease exceptions: Solitary bone/solitary extramedullary plasmocytoma ; Patients with non-secretory MM and non-measurable MM ; Evidence of central nervous system (CNS) involvement
• Medical history and Concurrent disease:
• Subjects with prior (≤ 5 years) or concurrent invasive malignancies except the following: Adequately treated basal cell or squamous cell skin cancer ; Incidental finding of low grade (Gleason 3+3 or less) prostate cancer ; Any cancer from which the subject has been disease free for at least 3 years.
• Subject with known/underlying medical conditions that, in the investigator's opinion would make the administration of the study drug hazardous (ie: uncontrolled diabetes or uncontrolled coronary artery disease)
• Any uncontrolled or severe cardiovascular or pulmonary disease determined by the investigator including: NYHA functional classification III or IV congestive heart failure LVEF (Left Ventricular Ejection Fraction) ≥45% ; Uncontrolled angina, hypertension or arrhythmia Myocardial infarction in the past 6 months
• Subjects with grade 2 or greater peripheral neuropathy (as per NCI-CTCAEv4.0)
• Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 4 months after the last dose of any component of the treatment regimen. Or, subject is a man who plans to father a child while enrolled in this study or within 4 months after the last dose of any component of the treatment regimen.
• Known positive for HIV or active hepatitis B or C.
• Subjects with psychiatric illnesses or social situations that would preclude them understanding the informed consent, study compliance or the ability to tolerate study procedures and/or study therapy
• Subjects with known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) \< 50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 \<50% of predicted normal.
• Subjects with a history of moderate or severe persistent asthma within the past 2 years (see appendix), or with uncontrolled asthma of any classification at the time of screening (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
• Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of Ixazomib including difficulty swallowing.
• Physical and laboratory test findings:
• Patients on dialysis or with a Creatinine clearance \< 30mL/min
• SGOT or SGPT \>3ULN

Sponsors & Collaborators

• University Hospital, Caen: lead

Study Sites (1)

CHU CAEN Dept of Hematology

Caen, 14033, France

Location

Related Publications (1)

• Bobin A, Macro M, Touzeau C, Mariette C, Manier S, Brechignac S, Vincent L, Hebraud B, Decaux O, Schulman S, Lenoir C, Godmer P, Parienti JJ, Paul LPS, Briant A, Leleu X. A dexamethasone-free daratumumab-ixazomib regimen in frail elderly patients with relapsed or refractory multiple myeloma: Results of the IFM 2018-02 phase II study. Br J Haematol. 2026 May 7. doi: 10.1111/bjh.70512. Online ahead of print.

  PMID: 42097596 RESULT

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; daratumumab

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

Study Design

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

Model Details: We plan a single-arm non-randomized open label phase II study with a Fleming one stage hypothesis testing for the primary endpoint of VGPR (Very Good Partial Response) + CR (Complete Response) Rate during the twelve months follow-up. The efficacy of Daratumumab plus Ixazomib will be evaluated in comparison to a minimally effective lower threshold level of VGPR + CR.

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: November 28, 2018
• Study Start: February 7, 2019
• Primary Completion: September 15, 2022
• Study Completion: April 28, 2024
• Last Updated: May 13, 2026

Record last verified: 2026-05

Locations

FR (1)