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Multi-center, Open-label, Phase 1b Study in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)

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ClinicalTrials.gov Identifier: NCT04045795
Recruitment Status : Recruiting
First Posted : August 6, 2019
Last Update Posted : August 9, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objectives:

  • To evaluate the safety and tolerability of isatuximab administered subcutaneously (SC) versus intravenously (IV)
  • To evaluate the pharmacokinetics (PK) of SC and IV isatuximab

Secondary Objectives:

  • To estimate absolute bioavailability of SC and IV isatuximab
  • To measure receptor occupancy (RO) after isatuximab SC versus IV administration
  • To assess efficacy of isatuximab after SC and IV administration
  • To assess patient expectations prior to and patient experience and satisfaction after SC administration
  • To evaluate potential immunogenicity of SC or IV isatuximab

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: isatuximab SAR650984 Drug: pomalidomide Drug: dexamethasone Phase 1

Detailed Description:
Total study duration is variable depending on treatment and follow-up periods, including 21 days of screening, and treatment period until disease progression, unacceptable adverse reaction or other reason for discontinuation. End of treatment will be 30 days after last administration of investigational medicinal product, or approximately 14 months after first study treatment administration.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-center, Open-label, Phase 1b Study to Assess the Pharmacokinetics, Safety, and Efficacy of Subcutaneous and Intravenous Isatuximab (SAR650984) in Combination With Pomalidomide and Dexamethasone, in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)
Actual Study Start Date : August 6, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Dose regimen 1
Isatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
Drug: isatuximab SAR650984
Pharmaceutical form: solution Route of administration: intravenous

Drug: pomalidomide
Pharmaceutical form: tablet Route of administration: oral

Drug: dexamethasone
Pharmaceutical form: tablet Route of administration: oral

Experimental: Dose regimen 2
Isatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
Drug: isatuximab SAR650984
Pharmaceutical form: solution Route of administration: intravenous

Drug: pomalidomide
Pharmaceutical form: tablet Route of administration: oral

Drug: dexamethasone
Pharmaceutical form: tablet Route of administration: oral

Experimental: Dose regimen 3
Isatuximab SC administration dose level 3 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
Drug: isatuximab SAR650984
Pharmaceutical form: solution Route of administration: intravenous

Drug: pomalidomide
Pharmaceutical form: tablet Route of administration: oral

Drug: dexamethasone
Pharmaceutical form: tablet Route of administration: oral

Experimental: Dose regimen 4
Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
Drug: isatuximab SAR650984
Pharmaceutical form: solution Route of administration: intravenous

Drug: pomalidomide
Pharmaceutical form: tablet Route of administration: oral

Drug: dexamethasone
Pharmaceutical form: tablet Route of administration: oral

Experimental: Dose regimen 5
Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
Drug: isatuximab SAR650984
Pharmaceutical form: solution Route of administration: intravenous

Drug: pomalidomide
Pharmaceutical form: tablet Route of administration: oral

Drug: dexamethasone
Pharmaceutical form: tablet Route of administration: oral




Primary Outcome Measures :
  1. Assessment of adverse events (AEs) [ Time Frame: Baseline to 30 days after last study treatment administration (up to approximately 14 months after first study treatment administration) ]
    Number of participants with adverse events

  2. Pharmacokinetic (PK) assessment: Ceoi [ Time Frame: Baseline to end of treatment (EOT) after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) ]
    Concentration observed at the end of infusion (Ceoi)

  3. PK assessment: Cmax [ Time Frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) ]
    Maximum concentration observed after the first infusion (Cmax)

  4. PK assessment: tmax [ Time Frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) ]
    Time to reach Cmax (tmax)

  5. PK assessment: Clast [ Time Frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) ]
    Last concentration observed above the lower limit of quantification after the first infusion (Clast)

  6. PK assessment: tlast [ Time Frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) ]
    Time of Clast (tlast)

  7. PK assessment: Ctrough [ Time Frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) ]
    Concentration observed just before treatment administration during repeated dosing (Ctrough)

  8. PK assessment: AUClast [ Time Frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) ]
    Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to time of the last concentration observed above the lower limit of quantification (ie, Clast) (AUClast)

  9. PK assessment: AUC0 T [ Time Frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) ]
    Area under the plasma concentration versus time curve calculated over the dosing interval T (168h or 336h) (AUC0 T)


Secondary Outcome Measures :
  1. Estimation of absolute bioavailability of isatuximab [ Time Frame: Day 8 ]
    Absolute bioavailability of isatuximab SC, expressed as a percentage, estimated from AUC0-168h obtained after intravenous (IV) and extravascular (EV) administration

  2. Overall response rate (ORR) [ Time Frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) ]
    ORR is the proportion of patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) using the IMWG response criteria

  3. Duration of response (DOR) [ Time Frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) ]
    Time from the date of the first response to the date of first progressive disease (PD) or death, whichever happens first

  4. Time to response (TTR) [ Time Frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) ]
    Time from the date of first study treatment to the first response

  5. Time to progression (TTP) [ Time Frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) ]
    Time from date of first study treatment to date of first documentation of progressive disease

  6. Overall survival (OS) [ Time Frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) ]
    Time from the date of first study treatment to date of death from any cause

  7. Clinical benefit rate (CBR) [ Time Frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) ]
    Proportion of patients with sCR, CR, VGPR, PR or minimal response (MR) according to IMWG criteria

  8. Progression free survival (PFS) [ Time Frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) ]
    Time from date of first study treatment to date of first documentation of progressive disease or death

  9. Comparison of patient expectations and satisfaction: Patient Expectations and Satisfaction Questionnaires [ Time Frame: Cycles 1 and 2 (28 days per Cycle), and 30 days after last isatuximab administration (up to approximately 14 months after first study treatment administration) ]
    Comparison of patient expectations and satisfaction will be assessed using Patient Expectations and Satisfaction Questionnaires before and after subcutaneous (SC) administration, where a score of 1 = not satisfied and a score of 5 = extremely satisfied

  10. Immunogenicity: Anti drug antibody levels [ Time Frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) ]
    Incidence of patients with anti drug antibodies against isatuximab

  11. Biomarker: Change in CD38 receptor occupancy [ Time Frame: At screening and at Day 1 of Cycle 2 (28 days per Cycle) (predose); to be stopped once the isatuximab SC dose has been selected. ]
    Change in CD38 receptor occupancy from baseline



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
  • Participant must be above 18 years of age inclusive, at the time of signing the informed consent.
  • Participant has been previously diagnosed with multiple myeloma (MM) based on standard criteria and currently requires treatment because MM has relapsed following a response, according to International Myeloma Working Group (IMWG) criteria.
  • Participant has received at least two previous therapies including lenalidomide and a proteasome inhibitor and has demonstrated disease progression on last therapy or after completion of the last therapy.
  • Participants with 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.
  • Serum free light chain (FLC) assay: Involved FLC assay ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).
  • Male or female: Contraceptive use by men or women.

Exclusion criteria:

  • Malignancy within 3 years prior to enrollment.
  • Eastern Cooperative Oncology Group (ECOG) performance status score >2.
  • Inadequate hematological, liver or renal function.
  • Serum calcium (corrected for albumin) level above the upper limit of normal (ULN) range.
  • Primary refractory or intolerant to prior therapy with any anti-CD38 mAb or had disease progression during anti-CD38 mAb, administered as last therapy.
  • Participant did not achieve a minimal response or better to at least one of the previous lines of treatment (ie, primary refractory disease is not eligible).
  • Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer.
  • Prior anti-cancer therapy within 14 days.
  • Any >Grade 1 adverse reaction unresolved from previous treatments according to the NCI-CTCAE v5.0. The presence of alopecia or peripheral neuropathy ≤ Grade 2 without pain is allowed.
  • Previous allogeneic stem cell transplantation with active Graft Versus Host Disease or being under immunosuppressive therapy in the last 2 months previously to the inclusion in the trial.
  • Daily requirement for corticosteroids.
  • Known to be HIV+ or to have hepatitis A, B or C active infection.
  • Active tuberculosis and severe infections requiring treatment with antibiotic parenteral administration.
  • Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results.
  • History of erythema multiforme or severe hypersensitivity to prior immunomodulatory drugs (IMiDs).
  • Hypersensitivity or history of intolerance to immunomodulatory drugs (IMiDs), dexamethasone, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and histamine H2 blockers or would prohibit further treatment with these agents.
  • Inability to tolerate thromboprophylaxis.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.


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): NCT04045795


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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Australia
Investigational Site Number 0360003 Recruiting
Richmond, Australia, 3121
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04045795     History of Changes
Other Study ID Numbers: TCD15484
2018‐001996‐19
U1111-1211-9525 ( Other Identifier: UTN )
First Posted: August 6, 2019    Key Record Dates
Last Update Posted: August 9, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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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
Dexamethasone
Dexamethasone acetate
Pomalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors