Testing JNJ-42756493 In Combination With Dexamethasone in Multiple Myeloma That Came Back After a Period of Improvement

NCT02952573 | Terminated Phase 2 DMC

• 1 other identifier: PM-MM003
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2 study to see how effective investigational drug, JNJ-42756493, is when given in combination with dexamethasone in two groups of patients with multiple myeloma (cancer of the plasma cells, a type of white blood cell present in bone marrow) that has relapsed (has come back after a period of improvement) or refractory (did not respond to standard treatment).

Conditions

Multiple Myeloma; Relapsed/Refractory

Outcome Measures

Primary Outcomes (3)

• Objective response rate (ORR)

  5 years

• Minimal response rate

  5 years

• Stable disease rate

  5 years

Secondary Outcomes (3)

• Incidence of toxicities

  5 years

• Progression free survival rate

  5 years

• Duration of response rate

  5 years

Study Arms (2)

FGFR3 wild-type

EXPERIMENTAL

JNJ-42756493: For the first cycle, 8 mg orally (by mouth), once each day for 14 days of each 28-day periods called cycles. Then dose of JNJ-42756493 may then be increased to 9 mg taken orally if no significant side effects related to JNJ-42756493 are seen during the first 14 days. Dexamethasone: 40 mg, orally, on days 1-4, 9-12, 17-20 for the first two cycles. Starting cycle 3, dexamethasone will be taken on days 1, 8, 15 and 22 (once weekly). Patients over the age of 75 will take a reduced dose of dexamethasone of 20 mg on starting cycle 1 on days 1-4, 9-12, 17-20 for the first two cycles. Starting cycle 3, dexamethasone will be taken on days 1, 8, 15 and 22 (once weekly).

Drug: JNJ-42756493; Drug: Dexamethasone

FGFR3 mutated

EXPERIMENTAL

JNJ-42756493: For the first cycle, 8 mg orally (by mouth), once each day for 14 days of each 28-day periods called cycles. Then dose of JNJ-42756493 may then be increased to 9 mg taken orally if no significant side effects related to JNJ-42756493 are seen during the first 14 days. Dexamethasone: 40 mg, orally, on days 1-4, 9-12, 17-20 for the first two cycles. Starting cycle 3, dexamethasone will be taken on days 1, 8, 15 and 22 (once weekly). Patients over the age of 75 will take a reduced dose of dexamethasone of 20 mg on starting cycle 1 on days 1-4, 9-12, 17-20 for the first two cycles. Starting cycle 3, dexamethasone will be taken on days 1, 8, 15 and 22 (once weekly).

Drug: JNJ-42756493; Drug: Dexamethasone

Interventions

JNJ-42756493 DRUG

Once daily dosing

Also known as: Erdafitinib

FGFR3 mutated; FGFR3 wild-type

Dexamethasone DRUG

Cycle 1 and 2: OD dosing on days 1-4, 9-12, and 17-20;Cycle 3: OD dosing on days 1, 8, 15, 22

Also known as: Apo- Dexamethasone

FGFR3 mutated; FGFR3 wild-type

Eligibility Criteria

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

You may qualify if:

• A diagnosis of MM and documentation of at least 1 prior line of therapy including proteasome and immunomodulatory agents.
• Documented lab results confirming FGFR3 expression and mutational status determined by a clinical grade, next generation sequencing platform approved by the Sponsor-Investigator, the results of which must be obtained prior to registration.
• Patients with measurable disease by laboratory studies for determining eligibility must be obtained within 28 days prior to start of study drug):
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or 2.
• Negative pregnancy status in women of childbearing potential must be confirmed within 7 days prior to start of study drug. Participants must use medically acceptable methods of birth control before the study entry, during the study, and until 3 months after taking the last dose of the study drug.
• Patient must sign the informed consent documents indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• Life Expectancy of ≥ 3 months.
• Able to take oral medications.
• Acceptable laboratory results must be met within 7 days of first study drug administration.

You may not qualify if:

• Patients in whom FGFR3 expression or mutational status cannot be determined.
• Chemotherapy, limited palliative radiotherapy or other anti-myeloma therapy within 14 days prior to the first dose of study drug. In addition, any treatment related toxicity should have recovered \< Grade 1 unless deemed to be irreversible.
• Patients who are receiving any other investigational agent.
• Patients with known CNS involvement, plasma cell leukemia or amyloidosis.
• Use of an investigational drug within 21 days or five-half-lives, whichever is shorter but not less than 14 days, preceding the first dose of study drug.
• History of allogeneic stem cell transplant.
• Autologous, peripheral stem cell transplant within 12 weeks of the first dose of study drug.
• Prior major surgical procedure or extensive radiation therapy within 4 weeks of the first dose of study treatment.
• Current use of corticosteroids, with the exception of inhaled or topical steroids.
• Previous or concurrent malignancies are allowed if it is clear that the patient is not symptomatic from the other tumor. The subject must not be receiving active therapy for the other tumor and the other tumor must be considered medically stable.
• Has a history of or current uncontrolled cardiovascular disease.
• Patients with evidence of mucosal or internal bleeding and/or platelet transfusion refractory. Patients cannot use growth factors within 7 days of start of study drug, or transfusion of blood or platelets within 7 days of start of study drug.
• Has impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions.
• Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluations.
• Any other condition that, in the Investigator's opinion, would contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Multiple Myeloma Research Consortium: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Croucher DC, Devasia AJ, Abelman DD, Mahdipour-Shirayeh A, Li Z, Erdmann N, Tiedemann R, Pugh TJ, Trudel S. Single-cell profiling of multiple myeloma reveals molecular response to FGFR3 inhibitor despite clinical progression. Cold Spring Harb Mol Case Stud. 2023 May 9;9(2):a006249. doi: 10.1101/mcs.a006249. Print 2023 Apr.

  PMID: 36639200 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

erdafitinib; Dexamethasone

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Suzanne Trudel, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2016
• First Posted: November 2, 2016
• Study Start: June 13, 2017
• Primary Completion: November 13, 2018
• Study Completion: November 13, 2018
• Last Updated: September 17, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)