A Study of Dabrafenib and/or Trametinib in Patients With Relapsed and/or Refractory Multiple Myeloma

NCT03091257 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 16-352
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a targeted therapy as a possible treatment for multiple myeloma. The names of the study drugs involved in this study are:

• Trametinib
• Dabrafenib

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Response rate by IMWG criteria

  100 weeks

Secondary Outcomes (1)

• Number of Participants with Severe Adverse Events

  100 weeks

Study Arms (3)

Dabrafenib

EXPERIMENTAL

Determine if mutation in BRAF, KRAS, NRAS * BRAF V600 mutated * Treat cohort with Dabrafenib * Analysis * Treat cohort with Dabrafenib

Drug: Dabrafenib

Dabrafenib and Trametinib

EXPERIMENTAL

Determine if mutation in BRAF, KRAS, NRAS * BRAF V600 mutated, BRAF/KRAS mutated, or BRAF/NRAS mutated, or BRAF non-V600 mutated * Treat cohort with Dabrafenib and Trametinib * Analysis * Treat cohort with Dabrafenib and Trametinib

Drug: Dabrafenib; Drug: Trametinib

Trametinib

EXPERIMENTAL

Determine if mutation in BRAF, KRAS, NRAS * KRAS or NRAS mutated * Treat cohort with Trametinib * Analysis * Treat cohort with Trametinib

Drug: Trametinib

Interventions

Trametinib DRUG

Administered Orally once daily

Also known as: Mekinist

Dabrafenib and Trametinib; Trametinib

Dabrafenib DRUG

Administered Orally BID

Also known as: Tafinlar

Dabrafenib; Dabrafenib and Trametinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a confirmed diagnosis of multiple myeloma as defined by the following criteria:
• Monoclonal plasma cells in the bone marrow greater than or equal to 10% and/or presence of a biopsy-proven plasmacytoma
• Monoclonal protein present in the serum and/or urine
• Measurable disease as defined by the following:
• IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level greater than or equal to 0.5 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours
• IgA multiple myeloma: Serum M-protein level greater than or equal to 0.5 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours
• IgD multiple myeloma: Serum M-protein level greater than or equal to 0.5 g/dL or urine M-protein level greater than or equal to 200 mg/24 hours
• Light chain multiple myeloma: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Participants must have myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains. Measurable disease is defined as one or more of the following: serum M-protein ≥0.5 g/dL, urine M-protein ≥200 mg/24 h, and/or serum FLC assay: involved FLC level ≥10 mg/dL with abnormal serum FLC ratio.
• Relapsed disease after at least 2 line of therapy
• Age ≥ 18 years years at the time of signing the informed consent form.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Participants must have sufficient organ and marrow function as defined below:
• Participants with platelet level ≥50,000/mm3, within 21 days of initiation of protocol therapy for patients in whom \<50% of bone marrow nucleated cells are plasma cells; or platelet count ≥30,000/mm3 for participants in whom \>50% of bone marrow nucleated cells are plasma cells. Transfusion within 7 days of screening is not allowed to meet platelet eligibility criteria.
• Participants with an absolute neutrophil count (ANC) ≥1000/mm3, within 21 days of initiation of protocol therapy. Growth factor within 7 days of screening is not allowed to meet ANC eligibility criteria.

You may not qualify if:

• Primary amyloidosis (AL) or myeloma complicated by amyloidosis
• Nonsecretory multiple myeloma based upon standard M-component criteria (ie, measurable serum/urine M-component) unless the baseline serum free light chain level is elevated. Patients with plasmacytomas with biopsy proven known mutations may be included as long as they have evaluable disease by imaging.
• Current use of a prohibited medication as described in Section 6.4.
• Participants with platelet level \<50,000/mm3, within 21 days of initiation of protocol therapy for patients in whom \<50% of bone marrow nucleated cells are plasma cells; or platelet count \<30,000/mm3 for participants in whom \>50% of bone marrow nucleated cells are plasma cells. Transfusion within 7 days of screening is not allowed to meet platelet eligibility criteria.
• Participants with an absolute neutrophil count (ANC) \<1000/mm3, within 21 days of initiation of protocol therapy. Growth factor within 7 days of screening is not allowed to meet ANC eligibility criteria.
• Participants with hemoglobin level \< 8 g/dL, within 21 days of initiation of protocol therapy. Transfusion may be used to meet hemoglobin eligibility criteria.
• Hepatic impairment, defined as total bilirubin \> 1.5 x institutional ULN (patients with benign hyperbilirubinemia (e.g., Gilbert's syndrome) are eligible.) or AST (SGOT), or ALT (SGPT), or alkaline phosphatase \> 2 x institutional ULN, within 21 days of initiation of protocol therapy.
• Renal insufficiency, defined as serum creatinine \>2.0 mg/dL.
• Participant had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class II, III or IV heart failure (see Appendix G), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities, or treatment refractory hypertension defined as a blood pressure of systolic \>140mmHg and/ or diastolic \> 90 mmHg which cannot be controlled by anti-hypertensive therapy. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
• A history or evidence of cardiovascular risk including any of the following:
• A QT interval corrected for heart rate using the Bazett's formula (QTcB; Appendix E) ≥ 480 msec;
• A history or evidence of current clinically significant uncontrolled arrhythmias; Clarification: Subjects with atrial fibrillation controlled for \>30 days prior to dosing are eligible.
• A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to alternate assignment.
• A history or evidence of current ≥ Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines (Appendix G);
• Patients with intra-cardiac defibrillators;

Sponsors & Collaborators

• Novartis: collaborator
• Multiple Myeloma Research Consortium: collaborator
• Barbara Ann Karmanos Cancer Institute: collaborator
• Massachusetts General Hospital: lead

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Noopur S Raje, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 17, 2017
• First Posted: March 27, 2017
• Study Start: June 21, 2017
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): September 15, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)