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

Study Purpose

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

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Males and females at least 18 years of age. 2. Voluntary written informed consent before performance of any study-related procedure. 3. 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.
4. 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). 5. Patients must have documented evidence of PD based on the investigator's determination of response as defined by the modified IMWG criteria. 6. Willingness and ability to participate in study procedures. 7. Patient has a Karnofsky Performance Status ≥ 70. 8. For patients experiencing toxicities resulting from previous therapy, the toxicities must be resolved or stabilized to ≤ Grade 1. 9. Patients with adequate bone marrow reserve, as evidenced by: 1. Absolute neutrophil count (ANC) ≥ 1.0×10^9/L. 2. 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). 10. All of the following results during Screening: 1. Hemoglobin level ≥8 g/dL (≥ 4.65 mmol/L) (transfusions are not permitted to reach this level). 2. Creatinine clearance ≥30 mL/min by CKD-EPI. 3. Alanine aminotransferase (ALT) level ≤ 2.5 times the upper limit of normal (ULN). 4. Aspartate aminotransferase (AST) level ≤ 2.5×ULN. 5. Total bilirubin level ≤ 1.5×ULN, (except for Gilbert Syndrome: direct bilirubin ≤1.5×ULN). 6. Serum calcium corrected for albumin ≤ 14.0 mg/dL (≤ 3.5 mmol/L), or free ionized calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L).

Exclusion Criteria:

1. Previous exposure to anti-CD38 antibodies or ixazomib. 2. 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. 3. 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. 4. Previous allogenic stem cell transplant; or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1. 5. Patient has received radiotherapy within 14 days of C1D1. Urgent localized radiotherapy for Spinal Cord Compression is allowed. 6. 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). 7. Clinical signs of meningeal involvement of MM. 8. 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. 9. Known active hepatitis A, B, or C. 10. Known HIV infection. 11. 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. 12. 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. 13. Patient has uncontrolled hypertension or hypertension requiring >2 medications for adequate control within 14 days to C1D1. 14. Patient has uncontrolled diabetes within 14 days to C1D1 or diabetes mellitus with > 2 episodes of ketoacidosis in the preceding 12 months from C1D1. 15. Patient has ongoing ≥ Grade 2 peripheral neuropathy. 16. Patient had ≥ Grade 3 rash during prior therapy. 17. Patient has had major surgery within 14 days prior to C1D1, or has not fully recovered from an earlier surgery, or has surgery planned during the time the patient is expected to participate in the study or within 2 weeks after the last dose of study drug administration. Note: patients with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery. 18. Pregnant or nursing women. 19. Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence. 20. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial. 21. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment. 22. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. 23. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03746652
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Hellenic Society of Hematology
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Evangelos Terpos, Prof.
Principal Investigator Affiliation Department of Clinical therapeutics, National and Kapodistrian University of Athens, School of medicine, Athens, Greece
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherOtherIndustry
Overall Status Not yet recruiting
Countries Greece
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Additional Details

This is a Phase 2, single-arm study of daratumumab in combination with ixazomib and dexamethasone as second line treatment for relapsed Multiple Myeloma patients initially treated with lenalidomide-based regimens. Daratumumab is a human IgG1ĸ monoclonal antibody that binds with high affinity to a unique epitope on CD38, a transmembrane glycoprotein. It is a targeted immunotherapy that attacks tumor cells that overexpress CD38, in a variety of hematological malignancies including multiple myeloma. Ixazomib is an orally administered proteasome inhibitor with anti-myeloma activity.

Arms & Interventions

Arms

Experimental: DId

Daratumumab, Ixazomib, Dexamethasone

Interventions

Drug: - Daratumumab, Ixazomib, Dexamethasone

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

General Hospital of Athens "Alexandra", Athens, Attica, Greece

Status

Address

General Hospital of Athens "Alexandra"

Athens, Attica, 11528

Site Contact

Evangelos Terpos, Prof.

infohaema@eae.gr

+302103381512