Clinical Trials /

SAR650984 in Combination With Carfilzomib for Treatment of Relapsed or Refractory Multiple Myeloma

NCT02332850

Description:

This study will be conducted as a standard Phase 1b, open-label, multi-center study of patients with relapsed and/or refractory Myeloma who have received at least two prior therapeutic treatments or regimens. Throughout the Phase I portion of this study, a standard 3+3 dose escalation design will be utilized. Two dosing cohorts will evaluate escalating doses SAR650984 (5mg/kg and 10 mg/kg Day 1 and 15 of each 28-day cycle) with standard dose Carfilzomib (20-27 mg/mg2). Once a safe dose is established, an expansion cohort will further evaluate safety and begin to assess activity of this combination (SAR650984 (5mg/kg or 10 mg/kg Day 1 and 15 of each 28-day cycle) with standard dose Carfilzomib). During the dose escalation portion of the study, the DLT period will be the first cycle (28 days) or from Day 1 through Day 28 of initial study treatment. Expansion Phase Cohort An expansion cohort will begin once the MTD of SAR650984 plus standard dose Carfilzomib is established. The Expansion Cohort will enroll 18 patients for additional safety and preliminary efficacy data of SAR650984 plus Carfilzomib at the MTD.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Unknown status

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: SAR650984 in Combination With Carfilzomib for Treatment of Relapsed or Refractory Multiple Myeloma
  • Official Title: A Phase Ib Study of SAR650984 (Anti-CD38 mAb) in Combination With Carfilzomib for the Treatment of Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 139511
  • NCT ID: NCT02332850

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
SAR650984Treatment
CarfilzomibTreatment

Purpose

This study will be conducted as a standard Phase 1b, open-label, multi-center study of patients with relapsed and/or refractory Myeloma who have received at least two prior therapeutic treatments or regimens. Throughout the Phase I portion of this study, a standard 3+3 dose escalation design will be utilized. Two dosing cohorts will evaluate escalating doses SAR650984 (5mg/kg and 10 mg/kg Day 1 and 15 of each 28-day cycle) with standard dose Carfilzomib (20-27 mg/mg2). Once a safe dose is established, an expansion cohort will further evaluate safety and begin to assess activity of this combination (SAR650984 (5mg/kg or 10 mg/kg Day 1 and 15 of each 28-day cycle) with standard dose Carfilzomib). During the dose escalation portion of the study, the DLT period will be the first cycle (28 days) or from Day 1 through Day 28 of initial study treatment. Expansion Phase Cohort An expansion cohort will begin once the MTD of SAR650984 plus standard dose Carfilzomib is established. The Expansion Cohort will enroll 18 patients for additional safety and preliminary efficacy data of SAR650984 plus Carfilzomib at the MTD.

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalSAR650984: 5 mg/kg or 10 mg/kg Day 1 and 15 of each 28-day cycle (escalating cohorts) Carfilzomib: standard dose (20-27 mg/m2)
  • SAR650984
  • Carfilzomib

Eligibility Criteria

        Inclusion Criteria:

          -  Males or females, age 18 years or older.

          -  Diagnosis of MM and documentation of treatment with an IMiD® and proteasome
             inhibitor. Must have had 2 prior regimens/lines of therapy but there is no maximum
             number of prior regimens and prior autologous bone marrow transplant is acceptable if
             > 12 weeks from transplantation. A line of therapy is defined as a course of therapy
             that is not interrupted by progressive disease. For example, induction therapy,
             autologous stem cell transplantation, and maintenance therapy without intervening
             progressive disease is one line of therapy.

          -  Confirmed evidence of relapse/disease progression from immediately prior MM therapy
             or refractory to the immediately prior treatment. Refractory disease is defined as
             those who are non-responsive (< minimal response) on active therapy or experience
             disease progression within 60 days after the discontinuation of therapy. Relapsed
             disease is defined as achievement of at least a minimal response followed by disease
             progression on therapy or within 60 days of discontinuing active therapy.

          -  Patients may have received prior Carfilzomib (sensitive, relapsed and refractory all
             eligible) but must be > 4 weeks from last dosing of Carfilzomib. In the expansion
             cohort, at least 10 patients will be required to be refractory to Carfilzomib
             (refractory defined as having evidence of disease progression while receiving
             Carfilzomib or within 60 days of stopping Carfilzomib therapy).

          -  Patients must have measurable disease defined as at least one of the following:

          -  Serum M-protein ≥0.5 g/dl (≥5 g/l)

          -  Urine M-protein ≥200 mg/24 h

          -  Serum FLC assay: Involved FLC level ≥10 mg/dl (≥100 mg/l) and an abnormal serum free
             light chain ratio (<0.26 or >1.65)

          -  Quantitative immunoglobulin > 500mg/dL, only for IgA and IgD myeloma when the protein
             electrophoresis under-represents disease burden.

          -  Biopsy proven plasmacytoma (should be measured within 28 days prior to initial
             investigational agent dosing).

          -  Subject has an ECOG ≤ 2 performance status OR Karnofsky ≥ 60% performance status.

          -  Females of childbearing potential (FCBP) - A female of childbearing potential is a
             sexually mature woman who: 1) has not undergone a hysterectomy or bilateral
             oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive
             months may be included if the patient is not pregnant by a negative serum β-human
             chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening.
             Pregnancy testing is not required for post-menopausal or surgically sterilized women.
             FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex
             condom during sexual contact with a FCBP even if they have had a successful
             vasectomy. Females must agree to avoid pregnancy during the study and must agree to
             use a medically acceptable method of birth control as determined by the study doctor
             while participating in the study and for at least 12 weeks after the last dose of
             study medication.

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of routine medical care with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care.

          -  Ability to understand the purpose and risks of the study and provide signed and dated
             informed consent and authorization to use protected health information (in accordance
             with national and local subject privacy regulations).

        Inclusion Clinical Laboratories Criteria

          -  The following laboratory results must be met within 7 days of study drug (treatment)
             administration

          -  Absolute neutrophil count (ANC) > 1,000 cells/dL (1.0 x 10e9/L) (Growth factor cannot
             be used within the previous 7 days)

          -  Hemoglobin ≥ 8.0 g/dl (without transfusion within the previous 7 days).

          -  Platelet count > 50,000 cells/dL (50 x 10e9/L)

          -  Creatinine clearance ≥ 30 mL/min (Cockcroft-Gault equation)

          -  Serum SGOT/AST or SGPT/ALT < 2.5 x upper limit of normal (ULN)

          -  Total bilirubin ≤ 1.5 x ULN

          -  Serum calcium (corrected for albumin) level at or below the ULN range (treatment of
             hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal
             with standard treatment) prior to study therapy initiation.

          -  Left ventricular ejection fraction; LVEF ≥40% (By echocardiogram or MUGA testing).

        Exclusion Criteria:

          -  Diagnosed or treated for another malignancy within 3 years of enrollment, with the
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy, low-risk prostate cancer after curative therapy or
             complete resection of other advanced malignancy with the expectation that the patient
             has received curative therapy.

          -  Patient has received other investigational drugs with 21 days before enrollment (or
             must be > than four half-lives of the experimental agent). No prior SAR650984
             anti-CD38 antibody therapy allowed.

          -  History of significant cardiovascular disease unless the disease is well-controlled
             or history of myocardial infarction in the past 6 months. Significant cardiac
             diseases includes second/third degree heart block; significant conduction
             abnormalities, significant ischemic heart disease; QTc interval > 480 msec at
             baseline (using Bazett's formula and read by local cardiologist); poorly controlled
             hypertension; congestive heart failure of New York Heart Association (NYHA) Class II
             or worse (slight limitation of physical activity; comfortable at rest, but ordinary
             physical activity results in fatigue, palpitation, or dyspnea) and inability to
             tolerate intravenous hydration necessary for study therapy administration.

          -  Prior peripheral stem cell transplant within 12 weeks of the first dose of study
             treatment

          -  Daily requirement for corticosteroids (>10 mg prednisone QD or equivalent)

          -  Patients with evidence of significant mucosal or internal bleeding

          -  Prior radiation therapy or chemotherapy within 2 weeks or major surgical procedure
             within 4 weeks of the first dose of study treatment.

          -  Known active infection requiring parenteral or oral anti-infective treatment, once a
             patient has completed antibiotics and symptoms of infection have resolved to <Grade
             2, they are then considered eligible from an infection standpoint.

          -  Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or
             confuse follow-up evaluation.

          -  Any medical conditions that, in the Investigator's opinion, would impose excessive
             risk to the patient. Examples of such conditions include any pre-existing kidney
             disease (acute or chronic, unless renal insufficiency is felt to be secondary to MM),
             hypertension, active seizure disorder or pulmonary diseases that would impose
             excessive risk to the patient.

          -  Patient has hypersensitivity to any of the components of study therapy including
             required prophylactic medications.

          -  Known HIV seropositivity or active hepatitis B or C viral infection

          -  Neuropathy ≥Grade 3 or painful neuropathy ≥Grade 2 (National Cancer Institute Common
             Terminology Criteria for Adverse Events [NCI CTCAE] v4.03)

          -  Gastro-intestinal 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.
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events
Time Frame:Approximately up to 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Immunogenicity of SAR650984
Time Frame:Approximately up to 2 years
Safety Issue:
Description:Elisa assay for serum anibodies that bind to SAR650984
Measure:Overall response rate
Time Frame:Approximately up to 2 years
Safety Issue:
Description:
Measure:Clinical benefit response
Time Frame:Approximately up to 2 years
Safety Issue:
Description:measured by Complete Response + Very Good Partial Response + Partial Response + Minimal Remission/Response
Measure:Overall survival (OS)
Time Frame:1 year
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:Approximately up to 2 years
Safety Issue:
Description:
Measure:Time To Progression (TTP)
Time Frame:Approximately up to 2 years
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:Approximately up to 2 years
Safety Issue:
Description:
Measure:CD38 receptor density levels
Time Frame:Baseline
Safety Issue:
Description:
Measure:Receptor density levels
Time Frame:Within 60 days of last dose of study drug
Safety Issue:
Description:
Measure:Receptor occupancy
Time Frame:Within 60 days of last dose of study drug
Safety Issue:
Description:Analysis of the amount of SAR650984 bound to the CD38 receptor divided by CD38 receptor density by immunohistochemistry and flow cytometry

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of California, San Francisco

Trial Keywords

  • Relapsed
  • Refractory

Last Updated

June 30, 2015