NCT03732703

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 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
103

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Apr 2019

Longer than P75 for phase_1

Geographic Reach
1 country

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 29, 2018

Completed
9 days until next milestone

First Posted

Study publicly available on registry

November 7, 2018

Completed
5 months until next milestone

Study Start

First participant enrolled

April 1, 2019

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2024

Completed
Last Updated

February 14, 2025

Status Verified

February 1, 2025

Enrollment Period

5.8 years

First QC Date

October 29, 2018

Last Update Submit

February 12, 2025

Conditions

Keywords

Multiple MyelomaRelapsed RefractoryMultiple Myeloma Research Consortium (MMRC)Genomic ProfileMy DrugMultiple Myeloma Research Foundation

Outcome Measures

Primary Outcomes (2)

  • Overall Response Rate - Actionable Genetic Alteration

    • 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

    • 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

Study Arms (8)

Sub-Protocol A1

EXPERIMENTAL

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

Drug: Abemaciclib, dexamethasone, ixazomib, pomalidomide

Sub-Protocol B1

EXPERIMENTAL

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

Drug: Enasidenib, dexamethasone, ixazomib, pomalidomide

Sub-Protocol C1

EXPERIMENTAL

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

Drug: Cobimetinib, dexamethasone, ixazomib, pomalidomide

Sub-Protocol D1

EXPERIMENTAL

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

Drug: Erdafitinib, dexamethasone, ixazomib, pomalidomide

Sub-Protocol E1

EXPERIMENTAL

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

Sub-Protocol Y1

EXPERIMENTAL

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

Drug: Daratumumab, dexamethasone, ixazomib, pomalidomide

Sub-Protocol Y2

EXPERIMENTAL

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

Drug: Belantamab mafodotin, dexamethasone, ixazomib, pomalidomide

Sub-Protocol Y3

EXPERIMENTAL

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

Drug: Selinexor, dexamethasone, ixazomib, pomalidomide

Interventions

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.

Also known as: abemaciclib: Verzenio, LY2835219, ixazomib: Ninlaro, MLN2238, pomalidomide: Pomalyst
Sub-Protocol A1

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.

Also known as: enasidenib: AG221, IDHIFA, ixazomib: Ninlaro, MLN2238, pomalidomide: Pomalyst
Sub-Protocol B1

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.

Also known as: cobimetinib: Cotellic, GDC-0973, RG7420, ixazomib: Ninlaro, MLN2238, pomalidomide: Pomalyst
Sub-Protocol C1

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.

Also known as: erdafitinib: G-024, JNJ-42756493, JNJ-493, ixazomib: Ninlaro, MLN2238, pomalidomide: Pomalyst
Sub-Protocol D1

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.

Also known as: venetoclax: Venclexta: ABT-199, ixazomib: Ninlaro, MLN2238, pomalidomide: Pomalyst
Sub-Protocol E1

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

Also known as: daratumumab: Darzalex, ixazomib: Ninlaro, MLN2238, pomalidomide: Pomalyst
Sub-Protocol Y1

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

Also known as: Belantamab mafodotin: BLENREP, GSK2857916
Sub-Protocol Y2

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

Also known as: Selinexor: XPOVIO
Sub-Protocol Y3

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • 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
  • 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
  • +11 more criteria

You may not qualify if:

  • 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
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Mayo Clinic - Arizona

Phoenix, Arizona, 85054, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - Minnesota

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine Division of Medical Oncology

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07610, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Ohio State University College of Medicine

Columbus, Ohio, 43210, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (1)

  • 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.

    PMID: 27511158BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

abemaciclibDexamethasoneixazomibpomalidomideMLN2238enasidenibcobimetiniberdafitinibvenetoclaxdaratumumabbelantamab mafodotinselinexor

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

PregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, Fluorinated

Study Officials

  • Hearn J Cho, M.D., Ph.D.

    Multiple Myeloma Research Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Eight Arms with 38 patients per arm
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 29, 2018

First Posted

November 7, 2018

Study Start

April 1, 2019

Primary Completion

December 31, 2024

Study Completion

December 31, 2024

Last Updated

February 14, 2025

Record last verified: 2025-02

Data Sharing

IPD Sharing
Will not share

Locations