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Myeloma-Developing Regimens Using Genomics (MyDRUG) (MyDRUG)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03732703
Recruitment Status : Recruiting
First Posted : November 7, 2018
Last Update Posted : December 3, 2019
Sponsor:
Collaborators:
AbbVie
Celgene Corporation
Eli Lilly and Company
Genentech, Inc.
Janssen, LP
Takeda
Information provided by (Responsible Party):
Multiple Myeloma Research Consortium

Tracking Information
First Submitted Date  ICMJE October 29, 2018
First Posted Date  ICMJE November 7, 2018
Last Update Posted Date December 3, 2019
Actual Study Start Date  ICMJE April 1, 2019
Estimated Primary Completion Date February 10, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 2, 2018)
  • Overall Response Rate - Actionable Genetic Alteration [ Time Frame: Patients will be evaluated monthly for response from the start of the study until the date of documented disease progression, assessed up to 2 years ]
    • To evaluate the overall response rate (ORR) with targeted agents used in combination with backbone regimen ixazomib, pomalidomide and dexamethasone (IPd) in patients with an actionable genetic alteration per the International Myeloma Working Group [IMWG] consensus criteria (Kumar et al, 2016)
  • Overall Response Rate - Non-Actionable Genetic Alteration [ Time Frame: Patients will be evaluated monthly for response from the start of the study until the date of documented disease progression, assessed up to 2 years ]
    • To evaluate the ORR with agents used in combination with backbone (or IPd) regimen in patients with no actionable genetic alteration per IMWG consensus criteria (Kumar et al, 2016).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Myeloma-Developing Regimens Using Genomics (MyDRUG)
Official Title  ICMJE Myeloma-Developing Regimens Using Genomics (MyDRUG) (Genomics Guided Multi-arm Trial of Targeted Agents Alone or in Combination With a Backbone Regimen)
Brief Summary

The MyDRUG study is a type of Precision Medicine trial to treat patients with drugs targeted to affect specific genes that are mutated as part of the disease. Mutations in genes can lead to uncontrolled cell growth and cancer. Patients with a greater than 30% mutation to any of the following genes; CDKN2C, FGFR3, KRAS, NRAS, BRAF V600E, IDH2 or T(11;14) can be enrolled to one of the treatment arms. These arms have treatments specifically directed to the mutated genes. Patients that do not have a greater than 30% mutation to the genes listed can be enrolled to a non-actionable treatment arm.

The genetic sequencing of the patient's tumor is required via enrollment to the MMRF002 study: Clinical-grade Molecular Profiling of Patients with Multiple Myeloma and Related Plasma Cell Malignancies. (NCT02884102).

Detailed Description

The study will enroll 228 patients enrolled to one of six treatment arms. The study is open to patients relapsing with relapsed refractory multiple myeloma, who have

  • received at least one prior but no more than 3 prior therapies
  • exposed to both a PI and an IMiD
  • had early relapse after initial treatment. Relapse is defined as the IMWG uniform response criteria (Kumar et al, 2016). Early relapse as defined by at least one of the following:

    1. Relapse within 3 years post autologous stem cell transplantation (ASCT) on maintenance, or 18 months if unmaintained
    2. Relapse within 18 months of initial non-ASCT based therapy
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Six arms with 38 patients per arm
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed Refractory Multiple Myeloma
Intervention  ICMJE
  • Drug: Abemaciclib, dexamethasone, ixazomib, pomalidomide
    Patients with relapsed Multiple Myeloma will receive Abemaciclib and Dexamethasone for the first 2 cycles. Abemaciclib, Dexamethasone, Ixazomib and Pomalidomide from cycle 3 forward. Each cycle is 28 days long.
    Other Names:
    • abemaciclib: Verzenio, LY2835219
    • ixazomib: Ninlaro, MLN2238
    • pomalidomide: Pomalyst
  • Drug: Enasidenib, dexamethasone, ixazomib, pomalidomide
    Patients with relapsed Multiple Myeloma will receive Enasidenib and Dexamethasone for the first 2 cycles. Enasidenib, Dexamethasone, Ixazomib and Pomalidomide from cycle 3 forward. Each cycle is 28 days long.
    Other Names:
    • enasidenib: AG221, IDHIFA
    • ixazomib: Ninlaro, MLN2238
    • pomalidomide: Pomalyst
  • Drug: Cobimetinib, dexamethasone, ixazomib, pomalidomide
    Patients with relapsed Multiple Myeloma will receive Cobimetinib and Dexamethasone for the first 2 cycles. Cobimetinib, Dexamethasone, Ixazomib and Pomalidomide from cycle 3 forward. Each cycle is 28 days long.
    Other Names:
    • cobimetinib: Cotellic, GDC-0973, RG7420
    • ixazomib: Ninlaro, MLN2238
    • pomalidomide: Pomalyst
  • Drug: Erdafitinib, dexamethasone, ixazomib, pomalidomide
    Patients with relapsed Multiple Myeloma will receive Erdafitinib and Dexamethasone for the first 2 cycles. Erdafitinib, Dexamethasone, Ixazomib and Pomalidomide from cycle 3 forward. Each cycle is 28 days long.
    Other Names:
    • erdafitinib: G-024, JNJ-42756493, JNJ-493
    • ixazomib: Ninlaro, MLN2238
    • pomalidomide: Pomalyst
  • Drug: Venetoclax, dexamethasone, ixazomib, pomalidomide
    Patients with relapsed Multiple Myeloma will receive Venetoclax, Ixazomib, Pomalidomide and Dexamethasone every cycle. Each cycle is 28 days long.
    Other Names:
    • venetoclax: Venclexta: ABT-199
    • ixazomib: Ninlaro, MLN2238
    • pomalidomide: Pomalyst
  • Drug: Daratumumab, dexamethasone, ixazomib, pomalidomide
    Patients with relapsed Multiple Myeloma will receive Daratumumab, Ixazomib, Pomalidomide and Dexamethasone every cycle. Each cycle is 28 days long.
    Other Names:
    • daratumumab: Darzalex
    • ixazomib: Ninlaro, MLN2238
    • pomalidomide: Pomalyst
Study Arms  ICMJE
  • Experimental: Sub-Protocol A1
    Patients with CDK activating alteration receive Abemaciclib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
    Intervention: Drug: Abemaciclib, dexamethasone, ixazomib, pomalidomide
  • Experimental: Sub-Protocol B1
    Patients with IDH2 activating mutation receive Enasidenib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
    Intervention: Drug: Enasidenib, dexamethasone, ixazomib, pomalidomide
  • Experimental: Sub-Protocol C1
    Patients with the presence of RAF/RAS mutation receive Cobimetinib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
    Intervention: Drug: Cobimetinib, dexamethasone, ixazomib, pomalidomide
  • Experimental: Sub-Protocol D1
    Patients with presence of FGFR3 activating mutations receive Erdafitinib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
    Intervention: Drug: Erdafitinib, dexamethasone, ixazomib, pomalidomide
  • Experimental: Sub-Protocol E1
    Patients with Plasma cell Fluorescence In Situ Hybridization (FISH) test demonstrating presence of t(11;14) receive Venetoclax in combination with ixazomib, pomalidomide and dexamethasone (IPd)
    Intervention: Drug: Venetoclax, dexamethasone, ixazomib, pomalidomide
  • Experimental: Sub-Protocol Y1
    Patients with Non-Actionable Genetic Abnormality receive Daratumumab in combination with ixazomib, pomalidomide and dexamethasone (IPd)
    Intervention: Drug: Daratumumab, dexamethasone, ixazomib, pomalidomide
Publications * Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Bladé J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016 Aug;17(8):e328-e346. doi: 10.1016/S1470-2045(16)30206-6. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 2, 2018)
228
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 10, 2024
Estimated Primary Completion Date February 10, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Willing to be registered into the pomalidomide (POMALYST®) Risk Evaluation and Mitigation Strategy (REMS®) program
  • Enrolled in the MMRF002 Molecular Profiling Protocol (NCT02884102) with report less than 120 days old
  • Disease free of prior malignancies for ≥ 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or prostate cancer not requiring therapy
  • High risk patients with relapsed refractory multiple myeloma (RRMM), who have:

    • received at least one prior but no more than 3 prior therapies
    • exposed to both a PI and an IMiD
    • had early relapse after initial treatmentEarly relapse as defined by at least one of the following: (Relapse is defined as the IMWG uniform response)

      1. Within 3 years post autologous stem cell transplantation (ASCT) on maintenance, or 18 months if unmaintained
      2. Within 18 months of initial non-ASCT based therapy
  • Patients must have progressed after their most recent treatment and require therapy for myeloma
  • Females of reproductive potential must have a negative pregnancy test at baseline, be non-lactating, and willing to adhere to scheduled pregnancy testing
  • Females of reproductive potential and males must practice and acceptable method of birth control
  • Laboratory values obtained ≤ 14 days prior to registration:

    • Absolute neutrophil count (ANC) ≥ 1000/ul
    • Hemoglobin (Hgb) ≥ 8 g/dl
    • Platelet (PLT) ≥ 75,000/ul
    • Total bilirubin <1.5 x upper limit of normal (ULN) or if total bilirubin is >1.5 x ULN, the direct bilirubin must be ≤ 2.0 mg/dL
    • Aspartate aminotransferase (AST) <3 x ULN
    • Creatinine Clearance ≥ 30 mL/min

Measurable disease of Multiple Myeloma (MM) as defined by at least one of the following:

  • Serum monoclonal protein ≥1.0 g by protein electrophoresis
  • ≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis
  • Serum immunoglobulin free light chain (FLC) ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda FLC ratio
  • Monoclonal bone marrow plasmacytosis ≥30% (evaluable disease)

    • Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2
    • Ability to take aspirin, warfarin, or low molecular weight heparin

Sub-Protocol Inclusion Criteria:

Refer to each respective Sub Protocol for additional inclusion criteria.

Exclusion Criteria:

Patients will be ineligible for this study if they meet any one of the following criteria:

  • Aggressive multiple myeloma requiring immediate treatment as defined by:

    • Lactate dehydrogenase (LDH) > 2 times ULN
    • Presence of symptomatic extramedullary disease or central nervous system involvement
    • Hypercalcemia >11.5 mg/dl
    • Acute worsening of renal function (CrCl < 30 ml/min) directly related to myeloma relapse
    • Any neurological emergency related to myeloma
    • Clinical symptoms of hyperviscosity related to monoclonal protein
    • Involved serum free light chain > 100 mg/dL (1000 mg/L) in the setting of prior diagnosis of cast nephropathy
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days of enrolment
  • Known hypersensitivity or development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide, pomalidomide or similar drug. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of the agents
  • Prior Ixazomib/Pomalidomide/Dexamethasone combination therapy
  • Pregnant or breast-feeding females
  • Serious medical or psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance, interfere in the completion of treatment per protocol, or follow-up evaluation
  • Active hepatitis A, B or C viral infection or known human immunodeficiency virus (HIV) infection
  • Concurrent symptomatic amyloidosis or plasma cell leukemia
  • POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes]
  • Residual side effects to previous therapy > Grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy Grade 2 without pain are permitted)
  • Prior allogeneic or ASCT within 12 weeks of initiation of therapy. Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD)
  • Prior experimental therapy within 14 days of protocol treatment or 5 half-lives of the investigational drug, whichever is longer
  • Prior anticancer therapy within 14 days of initiation of protocol therapy (Dexamethasone/ 40mg/day) for a maximum of 4 days before screening is allowed
  • Prior major surgical procedure or radiation therapy within 4 weeks of the initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy).
  • Known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or Gastro Intestinal (GI) absorption of drugs administered orally
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
  • Other co-morbidity, which would interfere with patient's ability to participate in trial or that confounds the ability to interpret data from the study

Sub-Protocol Exclusion Criteria:

Refer to each respective Sub Protocol for additional exclusion criteria.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: MMRF Patient Support Center 866-603-6628 patientnavigator@themmrf.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03732703
Other Study ID Numbers  ICMJE MyDRUG (MMRC-085)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Multiple Myeloma Research Consortium
Study Sponsor  ICMJE Multiple Myeloma Research Consortium
Collaborators  ICMJE
  • AbbVie
  • Celgene Corporation
  • Eli Lilly and Company
  • Genentech, Inc.
  • Janssen, LP
  • Takeda
Investigators  ICMJE Not Provided
PRS Account Multiple Myeloma Research Consortium
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP