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

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Isatuximab
Carfilzomib
Dexamethasone
Sponsored by
Thomas Martin, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Relapsed, Refractory

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Males or females, age 18 years or older
  2. Diagnosis of multiple myeloma (MM) and documentation of treatment

    • ARM 1: Must have prior exposure to an immunomodulatory drug (IMiD) and proteasome inhibitor (PI) and 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; patients may have received prior carfilzomib (sensitive, relapsed and refractory [having progressed while receiving carfilzomib or within 60 days of stopping carfilzomib] are all eligible), but must be > 4 weeks from last dosing of carfilzomib
    • ARM 2: Must have had at least 1 but no more than 3 prior lines of anti-myeloma therapy; may be refractory to lenalidomide but sensitive to carfilzomib; prior exposure to carfilzomib is allowed but may not be refractory to carfilzomib; subjects must be >= 8 weeks from last carfilzomib therapy
    • 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
  3. Confirmed evidence of relapse/disease progression from immediately prior MM therapy or relapsed and refractory to the immediately prior treatment; relapsed and refractory disease is defined as those who are non-responsive (< minimal response) on salvage therapy or experience disease progression within 60 days of last therapy in patients who have achieved an MR or better to previous therapy; relapsed disease is defined as previously treated myeloma that progresses and requires the initiation of salvage therapy but does not meet IMWG criteria for relapsed and refractory
  4. Patients may have received prior carfilzomib (sensitive, relapsed and refractory all eligible); response and duration of prior carfilzomib therapy must be known
  5. 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 hours (h)
    • Serum free light chain (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 for IgA or > 500mg/L for IgD, only for IgA and IgD myeloma (by nephelometry) when the protein electrophoresis under-represents disease burden
    • Biopsy proven plasmacytoma > 1x1 cm (should be measured within 28 days prior to initial investigational agent dosing)
  6. Subject has an Eastern Cooperative Oncology Group (ECOG) =< 2 performance status OR Karnofsky >= 60% performance status
  7. 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
    • Females of childbearing potential must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test with a sensitivity of at least 50 milli-international units per milliliter(mIU/mL), within 10-14 days of study start (during screening)
    • FCBP must also agree to ongoing pregnancy testing. Pregnancy testing is not required for post-menopausal or surgically sterilized women
    • 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 5 months after the last dose of study medication
  8. Men must agree to use contraception (i.e. a latex condom) during sexual contact with a FCBP even if they have had a successful vasectomy and agree to not donate sperm for 5 months after last study therapy (SAR650984, lenalidomide and carfilzomib).
  9. 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
  10. 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)
  11. For patients with platelets > 100,000 cells/ul (100x10^9/L) able to take aspirin daily as prophylactic anticoagulation therapy for ARM 2 (patients intolerant to aspirin may use warfarin, low-molecular-weight heparin or equivalent anti-platelet therapy)
  12. Inclusion Clinical Laboratories Criteria. The following laboratory results must be met:

    • 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 > 75,000 cells/dL (75 x 10e9/L)
    • Creatinine clearance >= 30 mL/min (Cockcroft-Gault equation)
    • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN)
    • Total bilirubin =< 1.5 x ULN (excluding Gilbert's)
    • 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 multigated acquisition scan (MUGA) testing)
    • Fasting glucose under control (< 150 mg/dL [8.3 mmol/L])

Exclusion Criteria:

Patients who have met all the inclusion criteria listed above will be screened for the following exclusion criteria:

  1. 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
  2. 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
  3. 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; 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
  4. Prior autologous or allogeneic peripheral stem cell transplant within 12 weeks of the first dose of study treatment
  5. Daily requirement for corticosteroids (> 10 mg prednisone once daily (QD) or equivalent)
  6. Patients with evidence of significant mucosal or internal bleeding
  7. Prior radiation therapy or chemotherapy within 2 weeks or major surgical procedure within 4 weeks of the first dose of study treatment
  8. 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
  9. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
  10. 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
  11. Patient has hypersensitivity to boron, mannitol sucrose, histidine (as base and hydrochloride salt) and polysorbate 80 or any of the components of study therapy including required prophylactic medications
  12. Known human immunodeficiency virus (HIV) seropositivity or active hepatitis B or C viral infection
  13. Neuropathy >= grade 3 or painful neuropathy >= grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version [v]4.03)
  14. 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

Sites / Locations

  • University of California, San FranciscoRecruiting
  • Colorado Blood Cancer InstituteRecruiting
  • Hackensack University Medical CenterRecruiting
  • Icahn School of Medicine at Mount Sinai
  • Sarah Cannon Cancer CenterRecruiting
  • Princess Margaret Cancer CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (20 mg dexamethasone, isatuximab, carfilzomib)

Arm II (40 mg dexamethasone, isatuximab, carfilzomib)

Arm Description

20 mg dexamethasone IV given on days 1, 8, 15, 22 (pre- SAR650984 and carfilzomib), then dexamethasone 4 IV or PO mg Day 2, 9, 16. All patients will receive a fixed dose of Isatuximab (SAR650984) according to their assigned dose cohort. Patients receive isatuximab IV over 4-6 hours on days 1 and 15 of every cycle for the starting cohort, and days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles. Carfilzomib IV will be administered over 10 minutes on days 1, 2, 8, 9, 15, and 16 . Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may continue treatment after 8 courses if clinical benefit is present at the investigator's discretion (carfilzomib may be switched to days 1, 2, 15, and 16 after 8 cycles per investigator discretion).

40 mg dexamethasone IV given on Days 1, 8, 15 and 22 (use as premed to isatuximab). All patients will receive a fixed dose of Isatuximab (SAR650984) according to the assigned dose. Patients receive isatuximab IV over 4-6 hours on day 1, 3-4 hours on Day 8, 15, and 22 of cycle 1 and then on days 1 and 15 of subsequent cycle (patients may be eligible for rapid siatuximab given over 75 minutes), and carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

ARM I: Incidence of Dose-Limiting Toxicities (DLT)
Treatment-related Adverse events resulting in a DLT will be summarized by maximum toxicity grade for each dose level of isatuximab.
ARM I: Maximum tolerated dose (MTD) of isatuximab
The MTD is defined as the dose level below the lowest dose that induces dose- limiting toxicity in at least one-third of patients Adverse events will be summarized by maximum toxicity grade and by dose level for each ARM of the trial using NCI CTCAE v4.03
ARM II: Overall Response Rate (ORR)
Overall response rate (ORR) as define by the International Myeloma Working Group (IMWG) uniform response criteria of patients obtaining Stringent Complete Remission (sCR), Complete Remission (CR), Very Good Partial Remission (VGPR), Partial Remission (PR), or Minimal Remission (MR)

Secondary Outcome Measures

ARM I: Pharmacokinetic (PK) profile of isatuximab
Individual plasma concentrations and PK parameters of SAR650984 will be tabulated with standard descriptive statistics. Pharmacokinetic analyses will be carried out in the Pharmacokinetics, Dynamics and Metabolism Department at Sanofi for SAR650984 and carfilzomib.
ARM I: Overall Response Rate (ORR)
Overall response rate; defined as sCR+CR+VGPR + PR utilizing IMWG Uniform Response Criteria
ARM I: Clinical benefit response (CBR)
defined as CR + VGPR + PR + minor response (MR), utilizing International Myeloma Working Group (IMWG) Uniform Response Criteria
ARM I: Incidence of isatuximab-specific antidrug antibodies (ADA)
Analysis to be performed by Sanofi-Oncology
ARM I: Percentage of bone marrow cells expressing cell surface determinant, CD38 and receptor density
Overall survival (OS)
Duration of time from start of treatment to death on study from any cause,
Progression Free Survival (PFS)
Duration of time from start of treatment to the first occurrence of disease progression or death on study from any cause, whichever occurs earlier,
Time To Progression (TTP)
Defined as the duration from start of treatment until the first occurrence of disease progression with deaths from causes other than disease progression, censored
Duration of Response (DOR)
The duration of overall response is defined as the time period when criteria are met for MR or better (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. The duration of CR is defined as the time when criteria are first met for CR until the first date that IMWG relapse is objectively documented
Changes in pharmacodynamics variables as they relate to dose, response, and toxicity of carfilzomib in combination with isatuximab
Changes from baseline in pharmacodynamic markers and proliferation markers, will be evaluated and summarized for each dose cohort.

Full Information

First Posted
December 12, 2014
Last Updated
March 21, 2023
Sponsor
Thomas Martin, MD
Collaborators
Amgen, Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT02332850
Brief Title
Phase Ib Study of SAR650984 in Combination With Carfilzomib for Treatment of Relapsed or Refractory Multiple Myeloma
Official Title
A Multi-ARM Phase Ib Study of SAR650984 (Isatuximab, an Anti-CD38 mAb) in Combination With Standard Carfilzomib, and High-dose Weekly Carfilzomib and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 21, 2015 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Thomas Martin, MD
Collaborators
Amgen, Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase Ib trial studies the side effects and best dose of isatuximab when given together with carfilzomib with or without dexamethasone and lenalidomide in treating patients with multiple myeloma that has returned after a period of improvement (relapsed) or has not respond to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as isatuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving isatuximab and carfilzomib with or without dexamethasone and lenalidomide may be a better treatment for patients with multiple myeloma.
Detailed Description
PRIMARY OBJECTIVES: ARM 1: To determine the maximum tolerated dose (MTD) of SAR650984 in combination with standard carfilzomib (Arm 1 is complete). ARM 2: To determine the safety AND efficacy (objective response rate (ORR)) of adding SAR650984 10mg/kg weekly x 4 doses then every other week in combination with weekly carfilzomib (70 mg/m2) and dexamethasone, in patients with relapsed or refractory myeloma. ORR will be defined using the International Myeloma Working Group (IMWG) uniform response criteria. SECONDARY OBJECTIVES: ARM 1: To evaluate the safety, including immunogenicity (ARM 1), of SAR650984 in combination with carfilzomib, in patients with relapsed or refractory myeloma after receiving 1+ prior lines of therapy. The severity, frequency and incidence of all toxicities will be assessed. To evaluate the pharmacokinetics (PK) of SAR650984 and carfilzomib when administered in ARM 1 (completed). To assess the relationship between clinical (adverse event and/or tumor response) effects and pharmacologic parameters (PK/PD), and/or biologic (correlative laboratory) results. To estimate the activity (ORR) using the International Myeloma Working Group (IMWG) defined response criteria of SAR650984 plus carfilzomib (ARM 1) To describe progression free survival (PFS), time to disease progression (TTP) and 1-year overall survival (OS) in patients treated with SAR650984 plus standard carfilzomib, and SAR650984 with weekly carfilzomib and dexamethasone. EXPANSION COHORTS: ARM 1: 1. To further evaluate safety, PK, PD and to estimate the anti-tumor activity (response rates) using IMWG defined response criteria of study therapy (SAR650984 plus carfilzomib). ARM 1 and 2: 1. To describe progression-free survival, 1-year OS, and TTP in patients with relapsed or refractory myeloma treated with these combinations. OUTLINE: This is a dose-escalation study of isatuximab. Patients are randomized to 1 of 2 arms. ARM I: Patients receive dexamethasone intravenously (IV) on days 1, 8, 15, and 22 of cycle 1, and orally (PO) or IV on days 1 and 15 of subsequent cycles. Patients receive isatuximab IV over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles, and carfilzomib IV over 10 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment after 8 cycles if clinical benefit is present at the investigator's discretion (carfilzomib may be switched to days 1, 2, 15, and 16 per investigator discretion). ARM II: Patients receive dexamethasone IV or PO on days 1, 8, 15, and 22, isatuximab IV over 4-6 hours on 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles, and carfilzomib IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 and 60 days and then every 3 months for up to 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Relapsed, Refractory

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
89 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (20 mg dexamethasone, isatuximab, carfilzomib)
Arm Type
Experimental
Arm Description
20 mg dexamethasone IV given on days 1, 8, 15, 22 (pre- SAR650984 and carfilzomib), then dexamethasone 4 IV or PO mg Day 2, 9, 16. All patients will receive a fixed dose of Isatuximab (SAR650984) according to their assigned dose cohort. Patients receive isatuximab IV over 4-6 hours on days 1 and 15 of every cycle for the starting cohort, and days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles. Carfilzomib IV will be administered over 10 minutes on days 1, 2, 8, 9, 15, and 16 . Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may continue treatment after 8 courses if clinical benefit is present at the investigator's discretion (carfilzomib may be switched to days 1, 2, 15, and 16 after 8 cycles per investigator discretion).
Arm Title
Arm II (40 mg dexamethasone, isatuximab, carfilzomib)
Arm Type
Experimental
Arm Description
40 mg dexamethasone IV given on Days 1, 8, 15 and 22 (use as premed to isatuximab). All patients will receive a fixed dose of Isatuximab (SAR650984) according to the assigned dose. Patients receive isatuximab IV over 4-6 hours on day 1, 3-4 hours on Day 8, 15, and 22 of cycle 1 and then on days 1 and 15 of subsequent cycle (patients may be eligible for rapid siatuximab given over 75 minutes), and carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
Isatuximab
Other Intervention Name(s)
SAR 650984
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
Kyprolis, PR-171
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Orgadrone, Spersadex, Visumetazone
Intervention Description
Given IV or PO
Primary Outcome Measure Information:
Title
ARM I: Incidence of Dose-Limiting Toxicities (DLT)
Description
Treatment-related Adverse events resulting in a DLT will be summarized by maximum toxicity grade for each dose level of isatuximab.
Time Frame
Up to 60 days of the last dose of study drug
Title
ARM I: Maximum tolerated dose (MTD) of isatuximab
Description
The MTD is defined as the dose level below the lowest dose that induces dose- limiting toxicity in at least one-third of patients Adverse events will be summarized by maximum toxicity grade and by dose level for each ARM of the trial using NCI CTCAE v4.03
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
ARM II: Overall Response Rate (ORR)
Description
Overall response rate (ORR) as define by the International Myeloma Working Group (IMWG) uniform response criteria of patients obtaining Stringent Complete Remission (sCR), Complete Remission (CR), Very Good Partial Remission (VGPR), Partial Remission (PR), or Minimal Remission (MR)
Time Frame
Up to 60 days of the last dose of study drug
Secondary Outcome Measure Information:
Title
ARM I: Pharmacokinetic (PK) profile of isatuximab
Description
Individual plasma concentrations and PK parameters of SAR650984 will be tabulated with standard descriptive statistics. Pharmacokinetic analyses will be carried out in the Pharmacokinetics, Dynamics and Metabolism Department at Sanofi for SAR650984 and carfilzomib.
Time Frame
Baseline, 2 hours mid-infusion, 4, 7, and 11 hours after end of infusion on day 1, days 2, 3, 8, and 15 of course 1, and 0 and 4 hours after end of infusion on day 1 of courses 2-8 (and 0 hours on day 15 of course 2 only)
Title
ARM I: Overall Response Rate (ORR)
Description
Overall response rate; defined as sCR+CR+VGPR + PR utilizing IMWG Uniform Response Criteria
Time Frame
Up to 60 days of the last dose of study drug
Title
ARM I: Clinical benefit response (CBR)
Description
defined as CR + VGPR + PR + minor response (MR), utilizing International Myeloma Working Group (IMWG) Uniform Response Criteria
Time Frame
Up to 60 days of the last dose of study drug
Title
ARM I: Incidence of isatuximab-specific antidrug antibodies (ADA)
Description
Analysis to be performed by Sanofi-Oncology
Time Frame
Up to 1 year
Title
ARM I: Percentage of bone marrow cells expressing cell surface determinant, CD38 and receptor density
Time Frame
Up to 30 days of the last dose of study drug
Title
Overall survival (OS)
Description
Duration of time from start of treatment to death on study from any cause,
Time Frame
assessed at 1, 2, and 3 years from start of treatment
Title
Progression Free Survival (PFS)
Description
Duration of time from start of treatment to the first occurrence of disease progression or death on study from any cause, whichever occurs earlier,
Time Frame
from start of treatment up to 1 year
Title
Time To Progression (TTP)
Description
Defined as the duration from start of treatment until the first occurrence of disease progression with deaths from causes other than disease progression, censored
Time Frame
from start of treatment up to 1 year
Title
Duration of Response (DOR)
Description
The duration of overall response is defined as the time period when criteria are met for MR or better (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. The duration of CR is defined as the time when criteria are first met for CR until the first date that IMWG relapse is objectively documented
Time Frame
up to 60 days of the last dose of study drug
Title
Changes in pharmacodynamics variables as they relate to dose, response, and toxicity of carfilzomib in combination with isatuximab
Description
Changes from baseline in pharmacodynamic markers and proliferation markers, will be evaluated and summarized for each dose cohort.
Time Frame
Baseline to up to 30 days of the last dose of study drug

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males or females, age 18 years or older Diagnosis of multiple myeloma (MM) and documentation of treatment ARM 1: Must have prior exposure to an immunomodulatory drug (IMiD) and proteasome inhibitor (PI) and 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; patients may have received prior carfilzomib (sensitive, relapsed and refractory [having progressed while receiving carfilzomib or within 60 days of stopping carfilzomib] are all eligible), but must be > 4 weeks from last dosing of carfilzomib ARM 2: Must have had at least 1 but no more than 3 prior lines of anti-myeloma therapy; may be refractory to lenalidomide but sensitive to carfilzomib; prior exposure to carfilzomib is allowed but may not be refractory to carfilzomib; subjects must be >= 8 weeks from last carfilzomib therapy 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 relapsed and refractory to the immediately prior treatment; relapsed and refractory disease is defined as those who are non-responsive (< minimal response) on salvage therapy or experience disease progression within 60 days of last therapy in patients who have achieved an MR or better to previous therapy; relapsed disease is defined as previously treated myeloma that progresses and requires the initiation of salvage therapy but does not meet IMWG criteria for relapsed and refractory Patients may have received prior carfilzomib (sensitive, relapsed and refractory all eligible); response and duration of prior carfilzomib therapy must be known 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 hours (h) Serum free light chain (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 for IgA or > 500mg/L for IgD, only for IgA and IgD myeloma (by nephelometry) when the protein electrophoresis under-represents disease burden Biopsy proven plasmacytoma > 1x1 cm (should be measured within 28 days prior to initial investigational agent dosing) Subject has an Eastern Cooperative Oncology Group (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 Females of childbearing potential must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test with a sensitivity of at least 50 milli-international units per milliliter(mIU/mL), within 10-14 days of study start (during screening) FCBP must also agree to ongoing pregnancy testing. Pregnancy testing is not required for post-menopausal or surgically sterilized women 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 5 months after the last dose of study medication Men must agree to use contraception (i.e. a latex condom) during sexual contact with a FCBP even if they have had a successful vasectomy and agree to not donate sperm for 5 months after last study therapy (SAR650984, lenalidomide and carfilzomib). 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) For patients with platelets > 100,000 cells/ul (100x10^9/L) able to take aspirin daily as prophylactic anticoagulation therapy for ARM 2 (patients intolerant to aspirin may use warfarin, low-molecular-weight heparin or equivalent anti-platelet therapy) Inclusion Clinical Laboratories Criteria. The following laboratory results must be met: 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 > 75,000 cells/dL (75 x 10e9/L) Creatinine clearance >= 30 mL/min (Cockcroft-Gault equation) Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) Total bilirubin =< 1.5 x ULN (excluding Gilbert's) 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 multigated acquisition scan (MUGA) testing) Fasting glucose under control (< 150 mg/dL [8.3 mmol/L]) Exclusion Criteria: Patients who have met all the inclusion criteria listed above will be screened for the following 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; 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 autologous or allogeneic peripheral stem cell transplant within 12 weeks of the first dose of study treatment Daily requirement for corticosteroids (> 10 mg prednisone once daily (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 boron, mannitol sucrose, histidine (as base and hydrochloride salt) and polysorbate 80 or any of the components of study therapy including required prophylactic medications Known human immunodeficiency virus (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] version [v]4.03) 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Phu Lam
Phone
(415) 353-8337
Email
Phu.Lam@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Martin, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Phu Lam
Phone
415-353-8337
Email
Phu.Lam@ucsf.edu
Phone
877-827-3222
Email
cancertrials@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Thomas Martin, MD
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henning Schade, MD
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Vesole, MD
Phone
551-996-5900
Email
David.Vesole@hackensackmeridian.org
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Sarah Cannon Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jesus Berdeha, MD
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alla Kubant
Phone
(416) 946-4501 ext. 2080
Email
Alla.Kubant2@uhn.ca

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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