Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone as Salvage Therapy in Relapsed/Refractory Multiple Myeloma

NCT03590652 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 180638
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to determine the overall response rate of patients with Multiple Myeloma to the combination of Daratumumab, Ixazomib, Pomalidomide and Dexamethasone.

Conditions

Relapsed/Refractory Multiple Myeloma

Keywords

multiple myeloma; relapsed/refractory multiple myeloma; Daratumumab; Pomalidomide; Ixazomib; Dexamethasone; cancer; Phase 2; Darzalex; Pomalyst; Ninlaro; Decadron

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate

  Anti-cancer response as defined by the International Uniform Response Criteria Consensus Recommendations

  2 years

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Treatment-emergent Grade 2-5 adverse events (AEs) will be assessed using NCI CTCAE v4.03 toxicity criteria

  2 years

Secondary Outcomes (6)

• Clinical benefit rate

  2 years

• Progression free survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Time to progression

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Overall survival (OS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Minimal Residual Disease (MRD)

  1 year

Study Arms (1)

ixazomib, daratumumab, pomalidomide and dexamethasone

EXPERIMENTAL

Daratumumab will be administered at 16mg/kg IV weekly x 8 weeks, biweekly x 8 weeks, then monthly. Pomalidomide 4mg will be administered orally daily for days 1-21. Patients ≤ age 75 will receive a 40mg dose of dexamethasone, and those over the age of 75 may receive a 20mg dose of dexamethasone orally on days 1, 8, 15, and 22 (weekly). Ixazomib will be administered 4mg orally on days 1, 8 and 15.

Drug: Ixazomib; Drug: Pomalidomide; Drug: Dexamethasone; Drug: Daratumumab-Hyaluronidase-Fihj@1,800 Mg-30,000 Unit/15 mL@SUBCUT@VIAL (ML)

Interventions

Ixazomib DRUG

4mg PO days 1,8,15 on 28-day cycle

Also known as: Ninlaro

ixazomib, daratumumab, pomalidomide and dexamethasone

Pomalidomide DRUG

4mg days PO 1-21/28 days

Also known as: Pomalyst

ixazomib, daratumumab, pomalidomide and dexamethasone

Dexamethasone DRUG

40mg\*\* PO weekly \*\* starting dose for age \>75 may be 20mg

Also known as: Decadron

ixazomib, daratumumab, pomalidomide and dexamethasone

Daratumumab-Hyaluronidase-Fihj@1,800 Mg-30,000 Unit/15 mL@SUBCUT@VIAL (ML) DRUG

1800mg SQ weekly x 8 weeks, biweekly x 8 doses, then monthly

Also known as: Darzalex Faspro

ixazomib, daratumumab, pomalidomide and dexamethasone

Eligibility Criteria

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

You may qualify if:

• All participants must be registered into the mandatory POMALYST REMS program and be willing and able to comply with the requirements of the POMALYST REMS program.
• Confirmed diagnosis of Multiple Myeloma having received 1 and 3 prior lines of treatment
• Relapsed and/or refractory disease
• Measurable disease
• Life expectancy of more than 3 months
• ECOG performance status of 0, 1, or 2
• No prior progression on pomalidomide
• All pts must have received prior lenalidomide therapy and been determined to be relapsed and/or refractory.
• Adequate hepatic function
• Adequate renal function
• Additional Laboratory Requirements
• ANC ≥1.0 x 10\^9/L, Hgb ≥8 g/dL (transfusion permitted)
• Platelet count ≥75 x 10\^9/L (≥ 50x10\^9/L if bone marrow plasma cells are ≥50% of cellularity)
• Women of child-bearing potential and men with partners of child-bearing potential must agree to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity from the time of signing the informed consent for through 120 days after the last dose of study medication.
• Women of childbearing potential have negative pregnancy test within 72 hours of initiating study drug dosing.

You may not qualify if:

• Current or anticipated use of other investigational agents.
• Prior daratumumab or ixazomib use
• Patients who are refractory to pomalidom
• Non-secretory or hyposecretory multiple myeloma defined as:
• Plasma cell leukemia (\>2.0 x 10 9/L circulating plasma cells by standard differential)
• Waldenström's macroglobulinemia or IgM myeloma
• Known central nervous system involvement by multiple myeloma
• Radiotherapy to multiple sites or immunotherapy within 2 weeks before enrollment (localized radiotherapy to a single site at least 1 week before start is permissible)
• Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (t1/2) prior to first dose, whichever time is greater. Non-interventional trials (i.e. observational trials) are permitted at any time point
• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Major surgery within 3 weeks prior to first dose
• Myocardial infarction within 6 months prior to enrollment, NYHA (New York Heart Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
• Systemic treatment, within 14 days before the first dose of ixazomib, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort.
• Known or suspected HIV infection, known HIV seropositivity

Sponsors & Collaborators

• University of California, San Diego: lead
• Celgene: collaborator
• Takeda: collaborator
• Janssen, LP: collaborator

Study Sites (4)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California, Los Angeles

Los Angeles, California, 90024, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

University of California, San Francisco

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms

Interventions

ixazomib; pomalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; 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; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Caitlin Costello, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor of Medicine

Study Record Dates

• First Submitted: June 21, 2018
• First Posted: July 18, 2018
• Study Start: October 17, 2018
• Primary Completion: July 2, 2025
• Study Completion: July 2, 2025
• Last Updated: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)