Clinical Trials /

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

NCT03590652

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone as Salvage Therapy in Relapsed/Refractory Multiple Myeloma
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 180638
  • NCT ID: NCT03590652

Conditions

  • Relapsed/Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
IxazomibNinlaroixazomib, daratumumab, pomalidomide and dexamethasone
PomalidomidePomalystixazomib, daratumumab, pomalidomide and dexamethasone
DexamethasoneDecadronixazomib, daratumumab, pomalidomide and dexamethasone
DaratumumabDarzalexixazomib, daratumumab, pomalidomide and dexamethasone

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
ixazomib, daratumumab, pomalidomide and dexamethasoneExperimentalDaratumumab 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.
  • Ixazomib
  • Pomalidomide
  • Dexamethasone
  • Daratumumab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:Treatment-emergent Grade 2-5 adverse events (AEs) will be assessed using NCI CTCAE v4.03 toxicity criteria

Secondary Outcome Measures

Measure:Clinical benefit rate
Time Frame:2 years
Safety Issue:
Description:CBR: minimal response +ORR
Measure: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
Safety Issue:
Description:Progression-free survival (PFS) is defined as the duration of time from start of treatment until objective tumor progression or death
Measure: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
Safety Issue:
Description:Time to progression is defined as the duration of time from start of treatment until objective tumor progression.
Measure: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
Safety Issue:
Description:Overall survival is defined as the duration of time from start of treatment to death
Measure:Minimal Residual Disease (MRD)
Time Frame:1 year
Safety Issue:
Description:
Measure:Quality of life (QOL) scores
Time Frame:2 years
Safety Issue:
Description:Cancer Therapy Satisfaction Questionnaire and EORTC QLQ-MY20

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Caitlin Costello, MD

Trial Keywords

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

Last Updated

January 13, 2019