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

April 29, 2024 updated by: Caitlin Costello, MD, University of California, San Diego

Phase II Study of the Combination of Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone as Salvage Therapy in Relapsed/Refractory Multiple Myeloma A University of California Hematologic Malignancies Consortium Protocol (UCHMC1809)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

The drugs being used in this study are daratumumab ixazomib, pomalidomide, and dexamethasone. Ixazomib may stop the growth of cancer by interfering with proteasomes (the protein breakdown mechanism in the cells). Pomalidomide, and dexamethasone are standard drugs that can change and regulate the immune system and may stop cancer cells from growing. Both Ixazomib and Daratumumab are approved for use in Multiple Myeloma, but not in this combination.

Study Type

Interventional

Enrollment (Estimated)

46

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • UCSD Moores Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

    1. ANC ≥1.0 x 10^9/L, Hgb ≥8 g/dL (transfusion permitted)
    2. 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.
  • Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential even if they have had a successful vasectomy starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the POMALYST REMS program.
  • Subjects must agree to take enteric-coated aspirin 81 mg orally daily, or if history of prior thrombotic disease, must be fully anticoagulated with warfarin (INR 2-3) or be treated with full-dose, low molecular weight heparin, as if to treat deep venous thrombosis (DVT)/pulmonary embolism (PE) at the investigator's discretion.

Exclusion Criteria:

  • 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
  • Active hepatitis infection
  • Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  • Subjects with known or suspected light chain amyloidosis of any organ.
  • Known allergies, hypersensitivity, or intolerance to monoclonal antibodies or human proteins, Daratumumab, or its excipients. or known sensitivity to mammalian-derived products.
  • Has known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal
  • Has known moderate or severe persistent asthma within the past 2 years per asthma guidelines
  • Known gastrointestinal disease or procedure that could interfere with the oral absorption or tolerance of ixazomib or pomalidomide, including difficulty swallowing

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ixazomib, daratumumab, pomalidomide and dexamethasone
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
4mg PO days 1,8,15 on 28-day cycle
Other Names:
  • Ninlaro
Drug: Pomalidomide
4mg days PO 1-21/28 days
Other Names:
  • Pomalyst
Drug: Dexamethasone

40mg** PO weekly

** starting dose for age >75 may be 20mg

Other Names:
  • Decadron
Drug: Daratumumab-Hyaluronidase-Fihj@1,800 Mg-30,000 Unit/15 mL@SUBCUT@VIAL (ML)
1800mg SQ weekly x 8 weeks, biweekly x 8 doses, then monthly
Other Names:
  • Darzalex Faspro

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: 2 years
Treatment-emergent Grade 2-5 adverse events (AEs) will be assessed using NCI CTCAE v4.03 toxicity criteria
2 years
Overall Response Rate
Time Frame: 2 years
Anti-cancer response as defined by the International Uniform Response Criteria Consensus Recommendations
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical benefit rate
Time Frame: 2 years
CBR: minimal response +ORR
2 years
Progression free survival (PFS)
Time Frame: 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
Progression-free survival (PFS) is defined as the duration of time from start of treatment until objective tumor progression or death
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
Time Frame: 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 is defined as the duration of time from start of treatment until objective tumor 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)
Time Frame: 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 is defined as the duration of time from start of treatment to death
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
Quality of life (QOL) scores
Time Frame: 2 years
Cancer Therapy Satisfaction Questionnaire and EORTC QLQ-MY20
2 years
Minimal Residual Disease (MRD)
Time Frame: 1 year
Assessment on the presence of minimal residual disease for those in stringent complete response
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Diego

Collaborators

Takeda
Celgene
Janssen, LP

Investigators

  • Principal Investigator: Caitlin Costello, MD, University of California, San Diego

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 17, 2018

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

October 1, 2025

Study Registration Dates

First Submitted

June 21, 2018

First Submitted That Met QC Criteria

July 5, 2018

First Posted (Actual)

July 18, 2018

Study Record Updates

Last Update Posted (Actual)

May 1, 2024

Last Update Submitted That Met QC Criteria

April 29, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 180638

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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