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

September 9, 2021 updated by: Multiple Myeloma Research Consortium

Myeloma-Developing Regimens Using Genomics (MyDRUG) (Genomics Guided Multi-arm Trial of Targeted Agents Alone or in Combination With a Backbone Regimen)

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 25% 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 25% 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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study will enroll 228 patients enrolled to one of eight 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

Interventional

Enrollment (Anticipated)

228

Phase

  • Phase 2
  • Phase 1

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
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic - Arizona
        • Contact:
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital Cancer Center
        • Contact:
      • Boston, Massachusetts, United States, 02215
      • Boston, Massachusetts, United States, 02215
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Health System
        • Contact:
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Center
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic - Minnesota
        • Contact:
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine Division of Medical Oncology
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States, 07610
        • Recruiting
        • Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
      • New York, New York, United States, 10029
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University College of Medicine
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75390
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Withdrawn
        • Virginia Cancer Specialists

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

Genders Eligible for Study

All

Description

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 treatment Early relapse as defined by at least one of the following: (Relapse is defined as the IMWG uniform response)

      1. Relapse within 3 years of initiation of induction chemo therapy for post autologous stem cell transplantation (ASCT) followed by maintenance, or 18 months if unmaintained after ASCT
      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 ≥ 0.5 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.

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: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / 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:
  • ixazomib: Ninlaro, MLN2238
  • pomalidomide: Pomalyst
  • enasidenib: AG221, IDHIFA
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:
  • ixazomib: Ninlaro, MLN2238
  • pomalidomide: Pomalyst
  • cobimetinib: Cotellic, GDC-0973, RG7420
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:
  • ixazomib: Ninlaro, MLN2238
  • pomalidomide: Pomalyst
  • erdafitinib: G-024, JNJ-42756493, JNJ-493
EXPERIMENTAL: Sub-Protocol E1
Patients with t(11;14) translocation will be enrolled in arm E1 and randomized to the venetoclax or the IPd control arm. Patients with relapsed Multiple Myeloma will receive Venetoclax, Ixazomib, Pomalidomide and Dexamethasone every cycle. Each cycle is 28 days long.
Drug: Venetoclax, dexamethasone, ixazomib, pomalidomide
Patients with t(11;14) translocation will be enrolled in arm E1 and randomized to the venetoclax or the IPd control arm. Patients with relapsed Multiple Myeloma will receive Venetoclax, Ixazomib, Pomalidomide and Dexamethasone every cycle. Each cycle is 28 days long.
Other Names:
  • ixazomib: Ninlaro, MLN2238
  • pomalidomide: Pomalyst
  • venetoclax: Venclexta: ABT-199
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:
  • ixazomib: Ninlaro, MLN2238
  • pomalidomide: Pomalyst
  • daratumumab: Darzalex
EXPERIMENTAL: Sub-Protocol Y2
Patients with Non-Actionable Genetic Abnormality receive Belantamab mafodotin in combination with ixazomib, pomalidomide and dexamethasone (IPd)
Drug: Belantamab mafodotin, dexamethasone, ixazomib, pomalidomide
Patients with relapsed Multiple Myeloma will receive Belantamab mafodotin, Ixazomib, Pomalidomide and Dexamethasone every cycle. Each cycle is 28 days long.
Other Names:
  • Belantamab mafodotin: BLENREP, GSK2857916
EXPERIMENTAL: Sub-Protocol Y3
Patients with Non-Actionable Genetic Abnormality receive Selinexor in combination with ixazomib, pomalidomide and dexamethasone (IPd)
Drug: Selinexor, dexamethasone, ixazomib, pomalidomide
Patients with relapsed Multiple Myeloma will receive Selinexor, Ixazomib, Pomalidomide and Dexamethasone every cycle. Each cycle is 28 days long.
Other Names:
  • Selinexor: XPOVIO

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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
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).
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

Collaborators and Investigators

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

Sponsor

Multiple Myeloma Research Consortium

Collaborators

Eli Lilly and Company
GlaxoSmithKline
AbbVie
Takeda
Genentech, Inc.
Celgene Corporation
Janssen, LP
Karyopharm Therapeutics Inc

Investigators

  • Principal Investigator: Hearn J Cho, M.D., Ph.D., Multiple Myeloma Research Consortium
  • Principal Investigator: Daniel Auclair, Ph.D., Multiple Myeloma Research Consortium

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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)

April 1, 2019

Primary Completion (ANTICIPATED)

February 10, 2022

Study Completion (ANTICIPATED)

February 10, 2024

Study Registration Dates

First Submitted

October 29, 2018

First Submitted That Met QC Criteria

November 2, 2018

First Posted (ACTUAL)

November 7, 2018

Study Record Updates

Last Update Posted (ACTUAL)

September 10, 2021

Last Update Submitted That Met QC Criteria

September 9, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MyDRUG (MMRC-085)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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