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

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ClinicalTrials.gov Identifier: NCT03732703
Recruitment Status : Recruiting
First Posted : November 7, 2018
Last Update Posted : October 21, 2019
Sponsor:
Collaborators:
AbbVie
Celgene Corporation
Eli Lilly and Company
Genentech, Inc.
Janssen, LP
Takeda
Information provided by (Responsible Party):
Multiple Myeloma Research Consortium

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).


Condition or disease Intervention/treatment Phase
Relapsed Refractory Multiple Myeloma Drug: Abemaciclib, dexamethasone, ixazomib, pomalidomide Drug: Enasidenib, dexamethasone, ixazomib, pomalidomide Drug: Cobimetinib, dexamethasone, ixazomib, pomalidomide Drug: Erdafitinib, dexamethasone, ixazomib, pomalidomide Drug: Venetoclax, dexamethasone, ixazomib, pomalidomide Drug: Daratumumab, dexamethasone, ixazomib, pomalidomide Phase 1 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 228 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Six arms with 38 patients per arm
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Myeloma-Developing Regimens Using Genomics (MyDRUG) (Genomics Guided Multi-arm Trial of Targeted Agents Alone or in Combination With a Backbone Regimen)
Actual Study Start Date : April 1, 2019
Estimated Primary Completion Date : February 10, 2022
Estimated Study Completion Date : February 10, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Sub-Protocol A1
Patients with CDK activating alteration receive Abemaciclib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
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

Experimental: Sub-Protocol B1
Patients with IDH2 activating mutation receive Enasidenib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
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

Experimental: Sub-Protocol C1
Patients with the presence of RAF/RAS mutation receive Cobimetinib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
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

Experimental: Sub-Protocol D1
Patients with presence of FGFR3 activating mutations receive Erdafitinib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
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

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)
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

Experimental: Sub-Protocol Y1
Patients with Non-Actionable Genetic Abnormality receive Daratumumab in combination with ixazomib, pomalidomide and dexamethasone (IPd)
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




Primary Outcome Measures :
  1. 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)

  2. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • 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.


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): NCT03732703


Contacts
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Contact: MMRF Patient Support Center 866-603-6628 patientnavigator@themmrf.org

Locations
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United States, Arizona
Mayo Clinic - Arizona Recruiting
Phoenix, Arizona, United States, 85054
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Massachusetts General Hospital Cancer Center Not yet recruiting
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Not yet recruiting
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Center Recruiting
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic - Minnesota Recruiting
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine Division of Medical Oncology Recruiting
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07610
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, North Carolina
Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28204
United States, Ohio
Ohio State University College of Medicine Recruiting
Columbus, Ohio, United States, 43210
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Multiple Myeloma Research Consortium
AbbVie
Celgene Corporation
Eli Lilly and Company
Genentech, Inc.
Janssen, LP
Takeda

Additional Information:
Publications:
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Responsible Party: Multiple Myeloma Research Consortium
ClinicalTrials.gov Identifier: NCT03732703     History of Changes
Other Study ID Numbers: MyDRUG (MMRC-085)
First Posted: November 7, 2018    Key Record Dates
Last Update Posted: October 21, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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 Multiple Myeloma Research Consortium:
Multiple Myeloma
Relapsed Refractory
Multiple Myeloma Research Consortium (MMRC)
Genomic Profile
My Drug
Multiple Myeloma Research Foundation
Additional relevant MeSH terms:
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Venetoclax
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
Daratumumab
Ixazomib
Pomalidomide
BB 1101
Antibodies, Monoclonal
Glycine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents