Multiple MyelomaPhase 1NCT03111992
Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Multiple Myeloma
A Phase 1 study testing PDR001, CJM112 and LCL161 in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 8 sites in 4 countries.
Trial summary
The purpose of this study is to assess the safety, tolerability, and identify the recommended doses of single agent CJM112, and of CJM112 or LCL161 in combination with PDR001, in patients with relapsed and/or refractory multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- PDR001, CJM112 and LCL161
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 18 Dec 2017to 2 Mar 2020
- Phase
- Phase 1
- 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
- Must be able to provide written informed consent before any screening procedures.
- Male or female patients ≥18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
- Patients with a confirmed diagnosis of multiple myeloma who have received two or more lines of therapy including an IMiD and PI, and are relapsed and/or refractory to their most recent line of therapy. Patients who have received a prior autologous bone marrow transplant and otherwise meet the inclusion criteria are eligible for this study.
- Must have measurable disease defined by at least 1 of the following 3 measurements:
- Serum M-protein ≥ 0.5 g/dL OR
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- Urine M-protein ≥ 200 mg/24 hours OR
- Serum free light chain (FLC) > 100 mg/L of involved FLC
- All patients must be willing to undergo a mandatory serial bone marrow aspirate and/or biopsy at screening and subsequently following treatment for the assessment of biomarker/pharmacodynamics and disease status. Exceptions may be considered after documented discussion with Novartis.
- Other inclusion criteria included in the protocol might apply.
Who cannot join
- Use of systemic chronic steroid therapy (≥10mg /day of prednisone or equivalent), or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal, or ophthalmic steroids are allowed.
- Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- Active, known or suspected autoimmune disease other than patients with vitiligo, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur.
- Patients with prior known toxicity attributed to PD-1 or PDL-1 directed therapy, which led to discontinuation of these agents, will be excluded from the PDR001 containing arms of the study.
- Patients with prior known toxicity from IL-17A directed therapy, which led to discontinuation of the study treatment, will be excluded from CJM112 containing arms of the study.
- Any of the following clinical laboratory results during screening (i.e., within 28 days before the first dose of study treatment):
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- Absolute neutrophil count (ANC) < 1,000/mm3 without growth factor support within 7 days prior to testing
- Platelet count < 75,000 mm3 without transfusion support within 7 days prior to testing
- Bilirubin > 1.5 times the upper limit of the normal range (ULN)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the ULN
- Calculated creatinine clearance < 30 ml/min according to Cockcroft-Gault equation Other exclusion criteria included in the protocol might apply.
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
Germany3 sites
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Kiel, 24105
United States2 sites
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Spain2 sites
Novartis Investigative Site
Madrid, 28006
Novartis Investigative Site
Salamanca, Castille and León, 37007
About this study
Official title: Phase I/Ib, Multi-center, Open-label, Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Relapsed and/or Refractory Multiple Myeloma
The purpose of this study is to assess the safety, tolerability, and identify the recommended doses of single agent CJM112, and of CJM112 or LCL161 in combination with PDR001, in patients with relapsed and/or refractory multiple myeloma.
- Conditions
- Multiple Myeloma
- Being tested
- PDR001, CJM112, LCL161
- Keywords
- Myeloma,, Multiple Myeloma,, Hematologic Diseases,, Myeloma, Multiple,, Myeloma-Multiple,, Programmed Cell Death 1 Receptor
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDR001Drug
Anti-PD1 antibody
CJM112Drug
Anti-IL-17A antibody
LCL161Drug
Oral small molecule SMAC-mimetic
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Dose escalation of single agent CJM112 Receives: Drug: CJM112 |
| Arm B | Experimental | Dose escalation of CJM112 in combination with a fixed dose of PDR001 Receives: Drug: PDR001; Drug: CJM112 |
| Arm C | Experimental | Dose escalation of LCL161 in combination with a fixed dose of PDR001 Receives: Drug: PDR001; Drug: LCL161 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients reporting dose limiting toxicities
number of patients reporting dose limiting toxicity
Measured: 2 months
The number of patients who experience a treatment-related adverse event after being treated with a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161
Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
Measured: 24 months
The number of patients requiring interruptions after a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161
Frequency of patients requiring a dose interruption
Measured: 24 months
The number of patients treated with single agent CJM112, or PDR001 in combination with either CJM112 or LCL161, who discontinued treatment
Frequency of patients discontinuing treatment.
Measured: 24 months
The number of patients requiring a dose reduction after a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161
Frequency of patients requiring a dose reduction.
Measured: 24 months
Secondary outcomes (10)
Immunogenicity of PDR001 and CJM112
Presence and/or concentration of anti-PDR001, and anti-CJM112 antibodies
Measured: First 6 months of study treatment
Overall Response Rate (ORR)
Determine ORR in each arm of the study
Measured: 24 Months
Best Overall Response (BOR)
Determine BOR in each arm of the study
Measured: 24 Months
Progression Free Survival (PFS)
Determine PFS in each arm of the study
Measured: 24 Months
Disease Control Rate (DCR)
Determine DCR in each arm of the study
Measured: 24 Months
AUC of PDR001, CJM112 and LCL161
AUC
Measured: 24 months
Cmax of PDR001, CJM112 and LCL161
Cmax
Measured: 24 months
Tmax of PDR001, CJM112 and LCL161
Tmax
Measured: 24 months
Half-life of PDR001, CJM112 and LCL161
Half-life
Measured: 24 months
Concentration vs time profile of PDR001, CJM112 and LCL161
Concentration vs time
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2017
- Study start18 Dec 2017
- Primary completion2 Mar 2020
- Study completion2 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study is comprised of 3 treatment arms: * Single agent CJM112 (Arm A) * A fixed dose of PDR001 in combination with CJM112 (Arm B) * A fixed dose of PDR001 in combination with LCL161 (Arm C) Patients may switch from treatment on Arm A to the corresponding CJM112 dose level on Arm B at the time of disease progression if that dose level has been declared safe, and if patients do not have any DLTs on single agent CJM112. Otherwise, patients will switch to a lower dose level that has been declared safe. No other cross-over between treatment arms is allowed.
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03111992
- Sponsor's protocol ID
- CPDR001X2106
- Status last verified
- Feb 2022
- First submitted
- 22 Mar 2017
- Last updated
- 9 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/Ib, Multi-center, Open-label, Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Relapsed and/or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT03111992
- Acronym / sponsor ID
- CPDR001X2106
- Conditions
- Multiple Myeloma
- Keywords
- Myeloma,, Multiple Myeloma,, Hematologic Diseases,, Myeloma, Multiple,, Myeloma-Multiple,, Programmed Cell Death 1 Receptor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 18 Dec 2017 (actual)
- Primary completion
- 2 Mar 2020 (actual)
- Study completion
- 2 Mar 2020 (actual)
- First posted
- 13 Apr 2017 (actual)
- 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.
The purpose of this study is to assess the safety, tolerability, and identify the recommended doses of single agent CJM112, and of CJM112 or LCL161 in combination with PDR001, in patients with relapsed and/or refractory multiple myeloma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The study is comprised of 3 treatment arms: * Single agent CJM112 (Arm A) * A fixed dose of PDR001 in combination with CJM112 (Arm B) * A fixed dose of PDR001 in combination with LCL161 (Arm C) Patients may switch from treatment on Arm A to the corresponding CJM112 dose level on Arm B at the time of disease progression if that dose level has been declared safe, and if patients do not have any DLTs on single agent CJM112. Otherwise, patients will switch to a lower dose level that has been declared safe. No other cross-over between treatment arms is allowed.
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: CJM112Dose escalation of single agent CJM112 |
| Arm B | Experimental | Drug: PDR001, Drug: CJM112Dose escalation of CJM112 in combination with a fixed dose of PDR001 |
| Arm C | Experimental | Drug: PDR001, Drug: LCL161Dose escalation of LCL161 in combination with a fixed dose of PDR001 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Must be able to provide written informed consent before any screening procedures.
- Male or female patients ≥18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
- Patients with a confirmed diagnosis of multiple myeloma who have received two or more lines of therapy including an IMiD and PI, and are relapsed and/or refractory to their most recent line of therapy. Patients who have received a prior autologous bone marrow transplant and otherwise meet the inclusion criteria are eligible for this study.
- Must have measurable disease defined by at least 1 of the following 3 measurements:
Key exclusion criteria (11 listed)
- Use of systemic chronic steroid therapy (≥10mg /day of prednisone or equivalent), or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal, or ophthalmic steroids are allowed.
- Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- Active, known or suspected autoimmune disease other than patients with vitiligo, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur.
- Patients with prior known toxicity attributed to PD-1 or PDL-1 directed therapy, which led to discontinuation of these agents, will be excluded from the PDR001 containing arms of the study.
- Patients with prior known toxicity from IL-17A directed therapy, which led to discontinuation of the study treatment, will be excluded from CJM112 containing arms of the study.
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 |
|---|---|---|
| PDR001Anti-PD1 antibody | Drug | Arm B, Arm C |
| CJM112Anti-IL-17A antibody | Drug | Arm A, Arm B |
| LCL161Oral small molecule SMAC-mimetic | Drug | Arm C |
Primary outcome
Number of patients reporting dose limiting toxicities
Time frame: 2 months
number of patients reporting dose limiting toxicity
The number of patients who experience a treatment-related adverse event after being treated with a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161
Time frame: 24 months
Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
The number of patients requiring interruptions after a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161
Time frame: 24 months
Frequency of patients requiring a dose interruption
The number of patients treated with single agent CJM112, or PDR001 in combination with either CJM112 or LCL161, who discontinued treatment
Time frame: 24 months
Frequency of patients discontinuing treatment.
The number of patients requiring a dose reduction after a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161
Time frame: 24 months
Frequency of patients requiring a dose reduction.
10 secondary outcomes
Immunogenicity of PDR001 and CJM112
Time frame: First 6 months of study treatment
Overall Response Rate (ORR)
Time frame: 24 Months
Best Overall Response (BOR)
Time frame: 24 Months
Progression Free Survival (PFS)
Time frame: 24 Months
Disease Control Rate (DCR)
Time frame: 24 Months
AUC of PDR001, CJM112 and LCL161
Time frame: 24 months
Cmax of PDR001, CJM112 and LCL161
Time frame: 24 months
Tmax of PDR001, CJM112 and LCL161
Time frame: 24 months
Half-life of PDR001, CJM112 and LCL161
Time frame: 24 months
Concentration vs time profile of PDR001, CJM112 and LCL161
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2022.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Results for CPDR001X2106 can be found on the Novartis Clinical Trial Results Website.Link provided by the sponsor.
- 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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PDR001, CJM112 and LCL161 in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 8 sites in 4 countries.
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 10 inclusion and 11 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: finished, as of the sponsor's last update on 9 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany, United States, Spain, Italy. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of patients reporting dose limiting toxicities (time frame: 2 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Feb 2022.