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

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ClinicalTrials.gov Identifier: NCT02952573
Recruitment Status : Recruiting
First Posted : November 2, 2016
Last Update Posted : February 4, 2019
Sponsor:
Collaborator:
Multiple Myeloma Research Consortium
Information provided by (Responsible Party):
University Health Network, Toronto

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).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Relapsed/Refractory Drug: JNJ-42756493 Drug: Dexamethasone Phase 2

Detailed Description:

Participants in the study will be assigned to one of two groups: One group of participants will be FGFR3 wild-type (participants whose tumors have no mutations or changes of a gene called FGFR3) and the other group will be FGFR3 mutated (participants whose tumors have mutations of FGFR3).

Participants will receive JNJ-42756493 with dexamethasone for as long as their diseases do not progress (worsen) and they do not experience unacceptable side effects for a maximum of 24 cycles (approximately 22 months).

While on the study drugs, participants will be asked to visit the clinic about 2 times during Cycles 1 and 2 and once during Cycle 3 and subsequent cycles for tests and procedures.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Open Label, Multicenter, Trial of JNJ-42756493 In Combination With Dexamethasone For The Treatment Of FGFR3 Wild-type Or Mutation Positive Relapsed and/or Refractory Multiple Myeloma
Actual Study Start Date : June 13, 2017
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Experimental: FGFR3 wild-type

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
Once daily dosing

Drug: Dexamethasone
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

Experimental: FGFR3 mutated

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
Once daily dosing

Drug: Dexamethasone
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




Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 5 years ]
  2. Minimal response rate [ Time Frame: 5 years ]
  3. Stable disease rate [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. Incidence of toxicities [ Time Frame: 5 years ]
  2. Progression free survival rate [ Time Frame: 5 years ]
  3. Duration of response rate [ Time Frame: 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Received prior FGFR inhibitor treatment or if the subject has known allergies, hypersensitivity, or intolerance to JNJ-42756493 or its excipients.
  • Pregnant, breast feeding, or planning to become pregnant within 3 months after the last dose of study drug and males who plan to father a child while enrolled in this study or within 5 months after the last dose of study drug.
  • Known HIV or active hepatitis B or C viral infection.
  • History of cerebrovascular accident (CVA) within 6 months prior to registration.
  • Gastrointestinal abnormalities, including bowel obstruction, inability to take oral medication, requirement for intravenous (IV) alimentation, active peptic ulcer or prior surgical procedures or bowel resection affecting absorption.
  • Peripheral neuropathy ≥ Grade 2.
  • Has persistent phosphate level >ULN during screening (within 14 days of treatment and prior to Cycle 1 Day 1) despite medical management.
  • Any corneal or retinal abnormality likely to increase the risk of eye toxicity.
  • Patients that require the following prohibited therapy:

    1. Medicines known to have a risk of causing QTc prolongation and Torsades de Pointes
    2. Medications known to increase serum levels of phosphate and calcium
    3. Medications or substances known to be strong inhibitors or strong inducers of CYP3A4 or CYP2C9 before the recommended 5 half-life washout period

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02952573


Contacts
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Contact: Suzanne Trudel, M.D. 416-946-4566 suzanne.trudel@uhn.ca

Locations
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Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Suzanne Trudel, M.D.    416-946-4566      
Sponsors and Collaborators
University Health Network, Toronto
Multiple Myeloma Research Consortium
Investigators
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Principal Investigator: Suzanne Trudel, M.D. Princess Margaret Cancer Centre

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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02952573     History of Changes
Other Study ID Numbers: PM-MM003
First Posted: November 2, 2016    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors