Multiple MyelomaPhase 2NCT02952573
Testing JNJ-42756493 In Combination With Dexamethasone in Multiple Myeloma That Came Back After a Period of Improvement
A Phase 2 study testing JNJ-42756493 and Dexamethasone in people with Multiple Myeloma and Relapsed/Refractory, run by University Health Network, Toronto at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Relapsed/Refractory
- What is being tested?
- JNJ-42756493 and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 13 Jun 2017to 13 Nov 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- Life Expectancy of ≥ 3 months.
- Able to take oral medications.
- Acceptable laboratory results must be met within 7 days of first study drug administration.
Who cannot join
- 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.
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- 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:
- Medicines known to have a risk of causing QTc prolongation and Torsades de Pointes
- Medications known to increase serum levels of phosphate and calcium
- Medications or substances known to be strong inhibitors or strong inducers of CYP3A4 or CYP2C9 before the recommended 5 half-life washout period
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
Read the 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.
- Conditions
- Multiple Myeloma, Relapsed/Refractory
- Being tested
- JNJ-42756493, Dexamethasone
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JNJ-42756493Drug
Also called Erdafitinib
Once daily dosing
DexamethasoneDrug
Also called Apo- 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
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: JNJ-42756493; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
Measured: 5 years
Minimal response rate
Measured: 5 years
Stable disease rate
Measured: 5 years
Secondary outcomes (3)
Incidence of toxicities
Measured: 5 years
Progression free survival rate
Measured: 5 years
Duration of response rate
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2016 (estimated)
- Study start13 Jun 2017
- Primary completion13 Nov 2018
- Study completion13 Nov 2018
Why it stopped: Low patient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Multiple Myeloma Research Consortium
- Responsible party
- Sponsor
- Investigators
- Suzanne Trudel, M.D., Principal investigator, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02952573
- Sponsor's protocol ID
- PM-MM003
- Status last verified
- Sep 2020
- First submitted
- 31 Oct 2016
- Last updated
- 17 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36639200
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02952573
- Acronym / sponsor ID
- PM-MM003
- Conditions
- Multiple Myeloma, Relapsed/Refractory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low patient accrual
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Multiple Myeloma Research Consortium
- Study start
- 13 Jun 2017 (actual)
- Primary completion
- 13 Nov 2018 (actual)
- Study completion
- 13 Nov 2018 (actual)
- First posted
- 2 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FGFR3 wild-type | Experimental | Drug: JNJ-42756493, Drug: DexamethasoneJNJ-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). |
| FGFR3 mutated | Experimental | Drug: JNJ-42756493, Drug: DexamethasoneJNJ-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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JNJ-42756493Also: ErdafitinibOnce daily dosing | Drug | FGFR3 mutated, FGFR3 wild-type |
| DexamethasoneAlso: Apo- DexamethasoneCycle 1 and 2: OD dosing on days 1-4, 9-12, and 17-20;Cycle 3: OD dosing on days 1, 8, 15, 22 | Drug | FGFR3 mutated, FGFR3 wild-type |
Primary outcome
Objective response rate (ORR)
Time frame: 5 years
Minimal response rate
Time frame: 5 years
Stable disease rate
Time frame: 5 years
3 secondary outcomes
Incidence of toxicities
Time frame: 5 years
Progression free survival rate
Time frame: 5 years
Duration of response rate
Time frame: 5 years
Results and safety
The study was stopped early (reason given: Low patient accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2020.
- Derived from this study: PubMed 36639200Croucher 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suzanne Trudel, M.D. principal investigator
Princess Margaret Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing JNJ-42756493 and Dexamethasone in people with Multiple Myeloma and Relapsed/Refractory, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low patient accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02952573, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2020.