Plasma Cell MyelomaPhase 1NCT01749969
SAR650984 (Isatuximab), Lenalidomide, and Dexamethasone in Combination in RRMM Patients
A Phase 1 study testing isatuximab SAR650984, lenalidomide and dexamethasone in people with Plasma Cell Myeloma, run by Sanofi at 5 sites in United States.
Trial summary
Primary Objectives: To determine the maximum tolerated dose of SAR650984 (isatuximab) with lenalidomide and dexamethasone (LD) in patients with relapsed or refractory multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Plasma Cell Myeloma
- What is being tested?
- isatuximab SAR650984, lenalidomide and dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 5 sitesUnited States
- Study dates
- 6 Feb 2013to 20 Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients age 18 years or older. Diagnosis of multiple myeloma and documentation of at least 2 prior therapies (induction therapy, autologous stem cell transplant, consolidation and maintenance therapy is considered one prior therapy); there is no maximum number of prior regimens and prior bone marrow transplant is acceptable.
- Confirmed evidence of disease progression from immediately prior MM therapy or refractory to the immediately prior therapy.
- Patients may have received prior immunomodulatory drugs (IMiDs®) (eg, lenalidomide or thalidomide).
- Patients with measurable disease. Patients with a Karnofsky ≥60% performance status. Females of childbearing potential (FCBP). 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performance of any study-related procedure not part of routine medical care with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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).
- Able to take aspirin daily as prophylactic anti-coagulation therapy (patients intolerant to aspirin may use warfarin, low molecular weight heparin or equivalent anti-platelet therapy).
- Adequate organ function.
Who cannot join
- Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy.
- Prior anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, and immunotherapy) within 21 days except for alkylating agents (eg, melphalan) where 28 days will be required or participated in another clinical trial during the past 30 days.
- History of significant cardiovascular disease within the past 6 months, unless the disease is well-controlled.
- Prior autologous stem cell transplant within 12 weeks of the first dose of study treatment and/or prior allogeneic transplant within 1 year or has evidence of active graft-versus-host disease (GVHD) requiring >10 mg prednisone daily.
- Daily requirement for corticosteroids (>10 mg prednisone qd for 7 consecutive days) (except for inhalation corticosteroids and patients being treated for adrenal insufficiency/replacement therapy).
- Evidence of mucosal or internal bleeding. Prior radiation therapy or major surgical procedure within 4 weeks of the first dose of study treatment.
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- Known active infection requiring parenteral or oral anti-infective treatment. 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.
- Hypersensitivity to any of the components of study therapy that is not amenable to premedication with steroids and H2 blockers.
- Known human immunodeficiency virus (HIV) or active hepatitis B or C viral infection.
- Neuropathy ≥ Grade 3 or painful neuropathy ≥ Grade 2. 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.
- Pregnancy.
- The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Investigational Site Number 840003
Columbus, Ohio, 43210
Investigational Site Number 840005
New York, New York, 10021
Investigational Site Number 840004
San Francisco, California, 94117
Investigational Site Number 840002
St Louis, Missouri, 63110
Investigational Site Number 840001
Tampa, Florida, 33612
About this study
Official title: A Phase 1b Study of SAR650984 (Anti-CD38 mAb) in Combination With Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma
Primary Objectives:
- To determine the maximum tolerated dose of SAR650984 (isatuximab) with lenalidomide and dexamethasone (LD) in patients with relapsed or refractory multiple myeloma.
- Expansion Phase Only: To further evaluate preliminary evidence of antitumor activity (objective response rate [ORR]) of SAR650984 (isatuximab) in combination with LD using International Myeloma Working Group (IMWG) criteria.
Read more
Secondary Objectives:
- To evaluate the safety, including immunogenicity, of SAR650984 (isatuximab) in combination with LD in relapsed or refractory multiple myeloma. The severity, frequency and incidence of all toxicities will be assessed.
- To evaluate the pharmacokinetics (PK) of SAR650984 (isatuximab) when administered in combination with LD and the PK of lenalidomide in combination with SAR650984 and dexamethasone.
- To assess the relationship between clinical (adverse event [AE] and/or tumor response) effects and pharmacologic parameters (PK/pharmacodynamics), and/or biologic (correlative laboratory) results.
- For the dose expansion phase, estimate the activity (ORR) using IMWG defined response criteria of SAR650984 (isatuximab) plus LD.
- To describe progression-free survival (PFS) in patients treated with this combination.
Read the detailed description
The study duration for an individual patient will include a screening period for inclusion of up to 21 days, and at least 4 weeks of treatment in the absence of severe adverse reaction, dose limiting toxicity or disease progression plus up to 60 days post-treatment follow up. The treatment period may continue until disease progression, intolerable toxicity, or Investigator, sponsor, or patient decision to discontinue therapy. After study treatment discontinuation, an end of treatment (EOT) visit will be done at 30 days to assess safety, and at 30 and 60 days for anti-drug antibody (ADA) and PK. If the ADA is positive or inconclusive at day 60, then PK and ADA will be repeated every 30 days until ADA is negative. Patients who discontinue treatment for reasons other than progression of disease will be followed monthly until progression, initiation of subsequent therapy, or until the primary analysis cutoff date, whichever comes first.
- Conditions
- Plasma Cell Myeloma
- Being tested
- isatuximab SAR650984, lenalidomide, dexamethasone
- Keywords
- Anti-CD38 monoclonal antibody
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
isatuximab SAR650984Drug
Also called Sarclisa
Pharmaceutical form:solution Route of administration: intravenous
lenalidomideDrug
Also called Revlimid
Pharmaceutical form:capsules Route of administration: oral
dexamethasoneDrug
Pharmaceutical form:solution or tablet Route of administration: intravenous or oral
| Study group | Role | What they receive |
|---|---|---|
| SAR650984 (isatuximab) | Experimental | SAR650984 (isatuximab) (escalating dose) plus lenalidomide 25 mg on Days 1 to 21 plus dexamethasone 40 mg on Days 1, 8, 15, 22 in 28-day cycles for all cohorts up to disease progression.
For Q2W cohorts: SAR650984 (isatuximab) on Days 1 and 15 of every cycle. For QW/Q2W cohorts: SAR650984 (isatuximab) on Days 1, 8, 15, and 22 of first cycle and Days 1 and 15 of every subsequent cycle. Receives: Drug: isatuximab SAR650984; Drug: lenalidomide; Drug: dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with adverse events when treated with SAR650984 (isatuximab) in combination with LD
Measured: Up to 30 days for patients experiencing progressive disease and continuously while patients are on treatment
Secondary outcomes (10)
Preliminary assessment of overall response rate
Measured: 9 months from the last investigational medicinal product (IMP)/non-IMP (NIMP) administration
Preliminary assessment of progression-free survival (PFS)
Measured: Up to disease progression
Assessment of PK parameters - maximum concentration (Cmax)
Measured: Up to disease progression plus 60 days
Assessment of PK parameters - time to reach Cmax (Tmax)
Measured: Up to disease progression plus 60 days
Assessment of PK parameters - concentration observed at end of infusion (Ceoi)
Measured: Up to disease progression plus 60 days
Assessment of PK parameters - area under the plasma concentration versus time curve over the dosing interval (AUCtau)
Measured: Up to disease progression plus 60 days
Assessment of PK parameters - plasma concentration observed just before treatment administration during repeated dosing (Ctrough)
Measured: Up to disease progression plus 60 days
Number of CD38 receptors occupied by SAR650984 (isatuximab)
Measured: Up to disease progression plus 60 days
CD38 receptor density
Measured: Up to disease progression plus 60 days
Immunogenicity: Number of anti-SAR650984 (isatuximab) antibodies in response to SAR650984 (isatuximab)
Measured: Up to disease progression plus 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2012 (estimated)
- Study start6 Feb 2013
- Primary completion20 Jun 2023
- Study completion20 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01749969
- Sponsor's protocol ID
- TCD11863
- Other IDs
- U1111-1119-3107
- Status last verified
- Jul 2023
- First submitted
- 10 Dec 2012
- Last updated
- 13 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Sun H, Martin TG, Marra J, Kong D, Keats J, Mace S, Chiron M, Wolf JL, Venstrom JM, Rajalingam R. Individualized genetic makeup that controls natural killer cell function influences the efficacy of isatuximab immunotherapy in patients with multiple myeloma. J Immunother Cancer. 2021 Jul;9(7):e002958. doi: 10.1136/jitc-2021-002958.
PubMed 34272304Martin T, Baz R, Benson DM, Lendvai N, Wolf J, Munster P, Lesokhin AM, Wack C, Charpentier E, Campana F, Vij R. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017 Jun 22;129(25):3294-3303. doi: 10.1182/blood-2016-09-740787. Epub 2017 May 8.
PubMed 28483761
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of SAR650984 (Anti-CD38 mAb) in Combination With Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01749969
- Acronym / sponsor ID
- TCD11863
- Conditions
- Plasma Cell Myeloma
- Keywords
- Anti-CD38 monoclonal antibody
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 6 Feb 2013 (actual)
- Primary completion
- 20 Jun 2023 (actual)
- Study completion
- 20 Jun 2023 (actual)
- First posted
- 17 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objectives:
- To determine the maximum tolerated dose of SAR650984 (isatuximab) with lenalidomide and dexamethasone (LD) in patients with relapsed or refractory multiple myeloma.
- Expansion Phase Only: To further evaluate preliminary evidence of antitumor activity (objective response rate [ORR]) of SAR650984 (isatuximab) in combination with LD using International Myeloma Working Group (IMWG) criteria.
Secondary Objectives:
- To evaluate the safety, including immunogenicity, of SAR650984 (isatuximab) in combination with LD in relapsed or refractory multiple myeloma. The severity, frequency and incidence of all toxicities will be assessed.
- To evaluate the pharmacokinetics (PK) of SAR650984 (isatuximab) when administered in combination with LD and the PK of lenalidomide in combination with SAR650984 and dexamethasone.
- To assess the relationship between clinical (adverse event [AE] and/or tumor response) effects and pharmacologic parameters (PK/pharmacodynamics), and/or biologic (correlative laboratory) results.
- For the dose expansion phase, estimate the activity (ORR) using IMWG defined response criteria of SAR650984 (isatuximab) plus LD.
- To describe progression-free survival (PFS) in patients treated with this combination.
Detailed description
The study duration for an individual patient will include a screening period for inclusion of up to 21 days, and at least 4 weeks of treatment in the absence of severe adverse reaction, dose limiting toxicity or disease progression plus up to 60 days post-treatment follow up. The treatment period may continue until disease progression, intolerable toxicity, or Investigator, sponsor, or patient decision to discontinue therapy. After study treatment discontinuation, an end of treatment (EOT) visit will be done at 30 days to assess safety, and at 30 and 60 days for anti-drug antibody (ADA) and PK. If the ADA is positive or inconclusive at day 60, then PK and ADA will be repeated every 30 days until ADA is negative. Patients who discontinue treatment for reasons other than progression of disease will be followed monthly until progression, initiation of subsequent therapy, or until the primary analysis cutoff date, whichever comes first.
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SAR650984 (isatuximab) | Experimental | Drug: isatuximab SAR650984, Drug: lenalidomide, Drug: dexamethasoneSAR650984 (isatuximab) (escalating dose) plus lenalidomide 25 mg on Days 1 to 21 plus dexamethasone 40 mg on Days 1, 8, 15, 22 in 28-day cycles for all cohorts up to disease progression. For Q2W cohorts: SAR650984 (isatuximab) on Days 1 and 15 of every cycle. For QW/Q2W cohorts: SAR650984 (isatuximab) on Days 1, 8, 15, and 22 of first cycle and Days 1 and 15 of every subsequent cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female patients age 18 years or older. Diagnosis of multiple myeloma and documentation of at least 2 prior therapies (induction therapy, autologous stem cell transplant, consolidation and maintenance therapy is considered one prior therapy); there is no maximum number of prior regimens and prior bone marrow transplant is acceptable.
- Confirmed evidence of disease progression from immediately prior MM therapy or refractory to the immediately prior therapy.
- Patients may have received prior immunomodulatory drugs (IMiDs®) (eg, lenalidomide or thalidomide).
- Patients with measurable disease. Patients with a Karnofsky ≥60% performance status. Females of childbearing potential (FCBP). 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).
Key exclusion criteria (13 listed)
- Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy.
- Prior anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, and immunotherapy) within 21 days except for alkylating agents (eg, melphalan) where 28 days will be required or participated in another clinical trial during the past 30 days.
- History of significant cardiovascular disease within the past 6 months, unless the disease is well-controlled.
- Prior autologous stem cell transplant within 12 weeks of the first dose of study treatment and/or prior allogeneic transplant within 1 year or has evidence of active graft-versus-host disease (GVHD) requiring >10 mg prednisone daily.
- Daily requirement for corticosteroids (>10 mg prednisone qd for 7 consecutive days) (except for inhalation corticosteroids and patients being treated for adrenal insufficiency/replacement therapy).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| isatuximab SAR650984Also: SarclisaPharmaceutical form:solution Route of administration: intravenous | Drug | SAR650984 (isatuximab) |
| lenalidomideAlso: RevlimidPharmaceutical form:capsules Route of administration: oral | Drug | SAR650984 (isatuximab) |
| dexamethasonePharmaceutical form:solution or tablet Route of administration: intravenous or oral | Drug | SAR650984 (isatuximab) |
Primary outcome
Number of patients with adverse events when treated with SAR650984 (isatuximab) in combination with LD
Time frame: Up to 30 days for patients experiencing progressive disease and continuously while patients are on treatment
10 secondary outcomes
Preliminary assessment of overall response rate
Time frame: 9 months from the last investigational medicinal product (IMP)/non-IMP (NIMP) administration
Preliminary assessment of progression-free survival (PFS)
Time frame: Up to disease progression
Assessment of PK parameters - maximum concentration (Cmax)
Time frame: Up to disease progression plus 60 days
Assessment of PK parameters - time to reach Cmax (Tmax)
Time frame: Up to disease progression plus 60 days
Assessment of PK parameters - concentration observed at end of infusion (Ceoi)
Time frame: Up to disease progression plus 60 days
Assessment of PK parameters - area under the plasma concentration versus time curve over the dosing interval (AUCtau)
Time frame: Up to disease progression plus 60 days
Assessment of PK parameters - plasma concentration observed just before treatment administration during repeated dosing (Ctrough)
Time frame: Up to disease progression plus 60 days
Number of CD38 receptors occupied by SAR650984 (isatuximab)
Time frame: Up to disease progression plus 60 days
CD38 receptor density
Time frame: Up to disease progression plus 60 days
Immunogenicity: Number of anti-SAR650984 (isatuximab) antibodies in response to SAR650984 (isatuximab)
Time frame: Up to disease progression plus 60 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2023.
- Derived from this study: PubMed 34272304Sun H, Martin TG, Marra J, Kong D, Keats J, Mace S, Chiron M, Wolf JL, Venstrom JM, Rajalingam R. Individualized genetic makeup that controls natural killer cell function influences the efficacy of isatuximab immunotherapy in patients with multiple myeloma. J Immunother Cancer. 2021 Jul;9(7):e002958. doi: 10.1136/jitc-2021-002958.
- Derived from this study: PubMed 28483761Martin T, Baz R, Benson DM, Lendvai N, Wolf J, Munster P, Lesokhin AM, Wack C, Charpentier E, Campana F, Vij R. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017 Jun 22;129(25):3294-3303. doi: 10.1182/blood-2016-09-740787. Epub 2017 May 8.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing isatuximab SAR650984, lenalidomide and dexamethasone in people with Plasma Cell Myeloma, run by Sanofi at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with adverse events when treated with SAR650984 (isatuximab) in combination with LD (time frame: Up to 30 days for patients experiencing progressive disease and continuously while patients are on treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01749969, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2023.