Safety and Efficacy of Daratumumab in Combination With Ixazomib and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

NCT03746652 | Unknown Phase 2

• 1 other identifier: ΕΑΕ-2018/ΜΜ03
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the efficacy of daratumumab in combination with ixazomib and dexamethasone as second line treatment for relapsed Multiple Myeloma patients.

Conditions

Multiple Myeloma

Keywords

Second line treatment; Daratumumab; Ixazomib; Dexamethasone;

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as the proportion of patients who achieve a best response of PR or better, using modified IMWG criteria.

  From first day of treatment until end of study, documented progressive disease (PD), or death (approximately up to 36 months)

Secondary Outcomes (8)

• Evaluation of the hematologic and non-hematologic toxicity profile of the combination.

  From first day of treatment until end of study, PD, or death (approximately up to 36 months)

• Duration of response (DOR)

  From the date of initial documentation of a response (CR, VGPR or PR) to the date of first documented evidence of PD, as defined in the IMWG criteria (approximately up to 36 months)

• Time to disease progression (TTP)

  From C1D1 to the date of first documented evidence of PD, as defined in the IMWG criteria (approximately up to 36 months)

• Progression-free survival (PFS)

  From C1D1 to either PD, according to the IMWG criteria, or death, whichever occurs first (approximately up to 36 months)

• Overall survival (OS)

  From C1D1 to the date of death from any cause (approximately up to 36 months)

Study Arms (1)

DId

EXPERIMENTAL

Daratumumab, Ixazomib, Dexamethasone

Drug: Daratumumab, Ixazomib, Dexamethasone

Interventions

Daratumumab, Ixazomib, Dexamethasone DRUG

Daratumumab 16 mg/kg, Ixazomib 4 mg, Dexamethasone 40 mg

DId

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females at least 18 years of age.
• Voluntary written informed consent before performance of any study-related procedure.
• Relapsed patients with measurable disease parameters according to the IMWG:
• IgG multiple myeloma: Serum M-protein level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours, or
• IgA, IgD, IgE, IgM multiple myeloma: Serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or
• Light chain multiple myeloma, for patients without measurable disease in the serum or urine: Serum immunoglobulin FLC ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
• Patients who have received one prior regimen for MM based on lenalidomide (induction followed by any planned high dose therapy or consolidation or maintenance would be considered as one regimen).
• Patients must have documented evidence of PD based on the investigator's determination of response as defined by the modified IMWG criteria.
• Willingness and ability to participate in study procedures.
• Patient has a Karnofsky Performance Status ≥ 70.
• For patients experiencing toxicities resulting from previous therapy, the toxicities must be resolved or stabilized to ≤ Grade 1.
• Patients with adequate bone marrow reserve, as evidenced by:
• Absolute neutrophil count (ANC) ≥ 1.0×10\^9/L.
• Platelet count ≥ 75×10\^9/L for patients in whom \< 50% of bone marrow nucleated cells are plasma cells and ≥ 50×10\^9/L for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells (transfusions are not permitted to reach this level).
• All of the following results during Screening:

You may not qualify if:

• Previous exposure to anti-CD38 antibodies or ixazomib.
• Systemic treatment with or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort within 14 days before C1D1.
• Patient has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, prior to C1D1. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment before C1D1.
• Previous allogenic stem cell transplant; or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1.
• Patient has received radiotherapy within 14 days of C1D1. Urgent localized radiotherapy for Spinal Cord Compression is allowed.
• History of malignancy (other than MM) within 3 years before C1D1 (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other noninvasive lesion that in the opinion of the investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years).
• Clinical signs of meningeal involvement of MM.
• Patient has clinically significant cardiac disease, including: unstable angina or myocardial infarction within 6 months to C1D1, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless patient has a pacemaker, or ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) \> 470 msec.
• Known active hepatitis A, B, or C.
• Known HIV infection.
• Patient has a history of significant neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness or stroke; or COPD requiring \> 2 hospitalizations in the preceding 12 months from C1D1.
• Patient has plasma cell leukemia (\> 2.0×10\^9/L circulating plasma cells by standard differential) or Waldenström's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.
• Patient has uncontrolled hypertension or hypertension requiring \>2 medications for adequate control within 14 days to C1D1.
• Patient has uncontrolled diabetes within 14 days to C1D1 or diabetes mellitus with \> 2 episodes of ketoacidosis in the preceding 12 months from C1D1.
• Patient has ongoing ≥ Grade 2 peripheral neuropathy.

Sponsors & Collaborators

• Hellenic Society of Hematology: lead
• Janssen Pharmaceutica NV: collaborator
• Takeda: collaborator

Study Sites (1)

General Hospital of Athens "Alexandra"

Athens, Attica, 11528, Greece

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; ixazomib; Dexamethasone

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Evangelos Terpos, Prof.

  Department of Clinical therapeutics, National and Kapodistrian University of Athens, School of medicine, Athens, Greece

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Panayiotis Panayiotidis, Prof.

CONTACT

+302107211806; infohaema@eae.gr

Study Design

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

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 20, 2018
• Study Start: December 1, 2018
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: November 23, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)