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Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT03111992
Recruitment Status : Recruiting
First Posted : April 13, 2017
Last Update Posted : January 21, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE March 22, 2017
First Posted Date  ICMJE April 13, 2017
Last Update Posted Date January 21, 2019
Actual Study Start Date  ICMJE December 18, 2017
Estimated Primary Completion Date May 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 7, 2017)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03111992 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 7, 2017)
  • Immunogenicity of PDR001 and CJM112 [ Time Frame: First 6 months of study treatment ]
    Presence and/or concentration of anti-PDR001, and anti-CJM112 antibodies
  • Overall Response Rate (ORR) [ Time Frame: Every 4 weeks through 6 months, every 8 weeks through 12 months, then every 16 weeks until the patient progresses or is withdrawn from the study (an average of 6 months) ]
    Determine ORR in each arm of the study
  • Best Overall Response (BOR) [ Time Frame: Every 4 weeks through 6 months, every 8 weeks through 12 months, then every 16 weeks until the patient progresses or is withdrawn from the study (an average of 6 months) ]
    Determine BOR in each arm of the study
  • Progression Free Survival (PFS) [ Time Frame: Every 4 weeks through 6 months, every 8 weeks through 12 months, then every 16 weeks until the patient progresses or is withdrawn from the study (an average of 6 months) ]
    Determine PFS in each arm of the study
  • Disease Control Rate (DCR) [ Time Frame: Every 4 weeks through 6 months, every 8 weeks through 12 months, then every 16 weeks until the patient progresses or is withdrawn from the study (an average of 6 months) ]
    Determine DCR in each arm of the study
  • AUC of PDR001, CJM112 and LCL161 [ Time Frame: 24 months ]
    AUC
  • Cmax of PDR001, CJM112 and LCL161 [ Time Frame: 24 months ]
    Cmax
  • Tmax of PDR001, CJM112 and LCL161 [ Time Frame: 24 months ]
    Tmax
  • Half-life of PDR001, CJM112 and LCL161 [ Time Frame: 24 months ]
    Half-life
  • Concentration vs time profile of PDR001, CJM112 and LCL161 [ Time Frame: 24 months ]
    Concentration vs time
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Multiple Myeloma
Official Title  ICMJE 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
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: PDR001
    Anti-PD1 antibody
  • Drug: CJM112
    Anti-IL-17A antibody
  • Drug: LCL161
    Oral small molecule SMAC-mimetic
Study Arms
  • Experimental: Arm A
    Dose escalation of single agent CJM112
    Intervention: Drug: CJM112
  • Experimental: Arm B
    Dose escalation of CJM112 in combination with a fixed dose of PDR001
    Interventions:
    • Drug: PDR001
    • Drug: CJM112
  • Experimental: Arm C
    Dose escalation of LCL161 in combination with a fixed dose of PDR001
    Interventions:
    • Drug: PDR001
    • Drug: LCL161
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 7, 2017)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date May 27, 2020
Estimated Primary Completion Date May 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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):

    • 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Canada,   Germany,   Italy,   Spain,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03111992
Other Study ID Numbers  ICMJE CPDR001X2106
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP