Clinical Trials /

Myeloma-Developing Regimens Using Genomics (MyDRUG)

NCT03732703

Description:

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).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MyDRUG (MMRC-085)
  • NCT ID: NCT03732703

Conditions

  • Relapsed Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
Abemaciclib, dexamethasone, ixazomib, pomalidomideabemaciclib: Verzenio, LY2835219, ixazomib: Ninlaro, MLN2238, pomalidomide: PomalystSub-Protocol A1
Enasidenib, dexamethasone, ixazomib, pomalidomideenasidenib: AG221, IDHIFA, ixazomib: Ninlaro, MLN2238, pomalidomide: PomalystSub-Protocol B1
Cobimetinib, dexamethasone, ixazomib, pomalidomidecobimetinib: Cotellic, GDC-0973, RG7420, ixazomib: Ninlaro, MLN2238, pomalidomide: PomalystSub-Protocol C1
Erdafitinib, dexamethasone, ixazomib, pomalidomideerdafitinib: G-024, JNJ-42756493, JNJ-493, ixazomib: Ninlaro, MLN2238, pomalidomide: PomalystSub-Protocol D1
Venetoclax, dexamethasone, ixazomib, pomalidomidevenetoclax: Venclexta: ABT-199, ixazomib: Ninlaro, MLN2238, pomalidomide: PomalystSub-Protocol E1
Daratumumab, dexamethasone, ixazomib, pomalidomidedaratumumab: Darzalex, ixazomib: Ninlaro, MLN2238, pomalidomide: PomalystSub-Protocol Y1

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
Sub-Protocol A1ExperimentalPatients with CDK activating alteration receive Abemaciclib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
  • Abemaciclib, dexamethasone, ixazomib, pomalidomide
Sub-Protocol B1ExperimentalPatients with IDH2 activating mutation receive Enasidenib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
  • Enasidenib, dexamethasone, ixazomib, pomalidomide
Sub-Protocol C1ExperimentalPatients with the presence of RAF/RAS mutation receive Cobimetinib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
  • Cobimetinib, dexamethasone, ixazomib, pomalidomide
Sub-Protocol D1ExperimentalPatients with presence of FGFR3 activating mutations receive Erdafitinib in combination with ixazomib, pomalidomide and dexamethasone (IPd)
  • Erdafitinib, dexamethasone, ixazomib, pomalidomide
Sub-Protocol E1ExperimentalPatients 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)
  • Venetoclax, dexamethasone, ixazomib, pomalidomide
Sub-Protocol Y1ExperimentalPatients with Non-Actionable Genetic Abnormality receive Daratumumab in combination with ixazomib, pomalidomide and dexamethasone (IPd)
  • Daratumumab, dexamethasone, ixazomib, pomalidomide

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

Primary Outcome Measures

Measure: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
Safety Issue:
Description:• 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)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Multiple Myeloma Research Foundation

Trial Keywords

  • Multiple Myeloma
  • Relapsed Refractory
  • Multiple Myeloma Research Consortium (MMRC)
  • Genomic Profile
  • My Drug
  • Multiple Myeloma Research Foundation

Last Updated