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

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ClinicalTrials.gov Identifier: NCT03590652
Recruitment Status : Recruiting
First Posted : July 18, 2018
Last Update Posted : January 15, 2019
Sponsor:
Collaborators:
Celgene
Takeda
Janssen, LP
Information provided by (Responsible Party):
Caitlin Costello, MD, University of California, San Diego

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.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Multiple Myeloma Drug: Ixazomib Drug: Pomalidomide Drug: Dexamethasone Drug: Daratumumab Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 17, 2018
Estimated Primary Completion Date : October 1, 2020
Estimated Study Completion Date : October 1, 2021


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 Name: Ninlaro

Drug: Pomalidomide
4mg days PO 1-21/28 days
Other Name: Pomalyst

Drug: Dexamethasone

40mg** PO weekly

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

Other Name: Decadron

Drug: Daratumumab
16mg/kg IV weekly x 8 weeks, biweekly x 8 doses, then monthly
Other Name: Darzalex




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 2 years ]
  2. 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


Secondary Outcome Measures :
  1. Clinical benefit rate [ Time Frame: 2 years ]
    CBR: minimal response +ORR

  2. 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

  3. 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.

  4. 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

  5. Minimal Residual Disease (MRD) [ Time Frame: 1 year ]
  6. Quality of life (QOL) scores [ Time Frame: 2 years ]
    Cancer Therapy Satisfaction Questionnaire and EORTC QLQ-MY20



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03590652


Contacts
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Contact: Caitlin Costello, MD 858-822-6600 ccostello@ucsd.edu
Contact: Elaine Eng e1eng@ucsd.edu

Locations
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United States, California
UCSD Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Caitlin Costello, MD    858-822-6600    ccostello@ucsd.edu   
Contact: Jesika Reiner       jreiner@ucsd.edu   
Sponsors and Collaborators
Caitlin Costello, MD
Celgene
Takeda
Janssen, LP
Investigators
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Principal Investigator: Caitlin Costello, MD University of California, San Diego

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Responsible Party: Caitlin Costello, MD, Assistant Clinical Professor of Medicine, University of California, San Diego
ClinicalTrials.gov Identifier: NCT03590652     History of Changes
Other Study ID Numbers: 180638
First Posted: July 18, 2018    Key Record Dates
Last Update Posted: January 15, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Caitlin Costello, MD, University of California, San Diego:
multiple myeloma
relapsed/refractory multiple myeloma
Daratumumab
Pomalidomide
Ixazomib
Dexamethasone
cancer
Phase 2
Darzalex
Pomalyst
Ninlaro
Decadron
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Thalidomide
Dexamethasone
Dexamethasone acetate
Ixazomib
Daratumumab
Pomalidomide
BB 1101
Glycine
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids