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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 : August 9, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: PDR001 Drug: CJM112 Drug: LCL161 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
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
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
Estimated Study Start Date : August 14, 2017
Estimated Primary Completion Date : June 1, 2020
Estimated Study Completion Date : June 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Arm A
Dose escalation of single agent CJM112
Drug: CJM112
Anti-IL-17A antibody

Experimental: Arm B
Dose escalation of CJM112 in combination with a fixed dose of PDR001
Drug: PDR001
Anti-PD1 antibody

Drug: CJM112
Anti-IL-17A antibody

Experimental: Arm C
Dose escalation of LCL161 in combination with a fixed dose of PDR001
Drug: PDR001
Anti-PD1 antibody

Drug: LCL161
Oral small molecule SMAC-mimetic




Primary Outcome Measures :
  1. Number of patients reporting dose limiting toxicities [ Time Frame: 2 months ]
    number of patients reporting dose limiting toxicity

  2. 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

  3. 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

  4. 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.

  5. 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.


Secondary Outcome Measures :
  1. Immunogenicity of PDR001 and CJM112 [ Time Frame: First 6 months of study treatment ]
    Presence and/or concentration of anti-PDR001, and anti-CJM112 antibodies

  2. 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

  3. 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

  4. 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

  5. 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

  6. AUC of PDR001, CJM112 and LCL161 [ Time Frame: 24 months ]
    AUC

  7. Cmax of PDR001, CJM112 and LCL161 [ Time Frame: 24 months ]
    Cmax

  8. Tmax of PDR001, CJM112 and LCL161 [ Time Frame: 24 months ]
    Tmax

  9. Half-life of PDR001, CJM112 and LCL161 [ Time Frame: 24 months ]
    Half-life

  10. Concentration vs time profile of PDR001, CJM112 and LCL161 [ Time Frame: 24 months ]
    Concentration vs time



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:

  • 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.

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): NCT03111992


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
Canada, Quebec
Novartis Investigative Site Recruiting
Montreal, Quebec, Canada, H3T 1E2
Switzerland
Novartis Investigative Site Recruiting
Locarno, Switzerland, 6600
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03111992     History of Changes
Other Study ID Numbers: CPDR001X2106
First Posted: April 13, 2017    Key Record Dates
Last Update Posted: August 9, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Myeloma,
Multiple Myeloma,
Hematologic Diseases,
Myeloma, Multiple,
Myeloma-Multiple,
Programmed Cell Death 1 Receptor

Additional relevant MeSH terms:
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