Myeloma-Developing Regimens Using Genomics (MyDRUG)

NCT ID: NCT03732703

Last Updated: 2025-02-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

103 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-01

Study Completion Date

2024-12-31

Brief Summary

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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).

Detailed Description

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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

Conditions

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Relapsed Refractory Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Eight Arms with 38 patients per arm
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sub-Protocol A1

Patients with CDK activating alteration receive Abemaciclib in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Group Type EXPERIMENTAL

Abemaciclib, dexamethasone, ixazomib, pomalidomide

Intervention Type DRUG

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.

Sub-Protocol B1

Patients with IDH2 activating mutation receive Enasidenib in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Group Type EXPERIMENTAL

Enasidenib, dexamethasone, ixazomib, pomalidomide

Intervention Type DRUG

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.

Sub-Protocol C1

Patients with the presence of RAF/RAS mutation receive Cobimetinib in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Group Type EXPERIMENTAL

Cobimetinib, dexamethasone, ixazomib, pomalidomide

Intervention Type DRUG

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.

Sub-Protocol D1

Patients with presence of FGFR3 activating mutations receive Erdafitinib in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Group Type EXPERIMENTAL

Erdafitinib, dexamethasone, ixazomib, pomalidomide

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Venetoclax, dexamethasone, ixazomib, pomalidomide

Intervention Type DRUG

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.

Sub-Protocol Y1

Patients with Non-Actionable Genetic Abnormality receive Daratumumab in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Group Type EXPERIMENTAL

Daratumumab, dexamethasone, ixazomib, pomalidomide

Intervention Type DRUG

Patients with relapsed Multiple Myeloma will receive Daratumumab, Ixazomib, Pomalidomide and Dexamethasone every cycle. Each cycle is 28 days long.

Sub-Protocol Y2

Patients with Non-Actionable Genetic Abnormality receive Belantamab mafodotin in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Group Type EXPERIMENTAL

Belantamab mafodotin, dexamethasone, ixazomib, pomalidomide

Intervention Type DRUG

Patients with relapsed Multiple Myeloma will receive Belantamab mafodotin, Ixazomib, Pomalidomide and Dexamethasone every cycle. Each cycle is 28 days long.

Sub-Protocol Y3

Patients with Non-Actionable Genetic Abnormality receive Selinexor in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Group Type EXPERIMENTAL

Selinexor, dexamethasone, ixazomib, pomalidomide

Intervention Type DRUG

Patients with relapsed Multiple Myeloma will receive Selinexor, Ixazomib, Pomalidomide and Dexamethasone every cycle. Each cycle is 28 days long.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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abemaciclib: Verzenio, LY2835219 ixazomib: Ninlaro, MLN2238 pomalidomide: Pomalyst enasidenib: AG221, IDHIFA ixazomib: Ninlaro, MLN2238 pomalidomide: Pomalyst cobimetinib: Cotellic, GDC-0973, RG7420 ixazomib: Ninlaro, MLN2238 pomalidomide: Pomalyst erdafitinib: G-024, JNJ-42756493, JNJ-493 ixazomib: Ninlaro, MLN2238 pomalidomide: Pomalyst venetoclax: Venclexta: ABT-199 ixazomib: Ninlaro, MLN2238 pomalidomide: Pomalyst daratumumab: Darzalex ixazomib: Ninlaro, MLN2238 pomalidomide: Pomalyst Belantamab mafodotin: BLENREP, GSK2857916 Selinexor: XPOVIO

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie

INDUSTRY

Sponsor Role collaborator

Celgene Corporation

INDUSTRY

Sponsor Role collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Janssen, LP

INDUSTRY

Sponsor Role collaborator

Takeda

INDUSTRY

Sponsor Role collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role collaborator

Multiple Myeloma Research Consortium

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hearn J Cho, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Multiple Myeloma Research Consortium

Locations

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Mayo Clinic - Arizona

Phoenix, Arizona, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Karmanos Cancer Center

Detroit, Michigan, United States

Site Status

Mayo Clinic - Minnesota

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine Division of Medical Oncology

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Ohio State University College of Medicine

Columbus, Ohio, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Countries

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United States

References

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Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Blade 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.

Reference Type BACKGROUND
PMID: 27511158 (View on PubMed)

Other Identifiers

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MyDRUG (MMRC-085)

Identifier Type: -

Identifier Source: org_study_id

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