Plasma Cell Myeloma
Conditions
Keywords
Anti-CD38 monoclonal antibody
Brief summary
Primary Objectives: Part A: To evaluate the safety and determine the recommended dose of SAR650984 in combination with pomalidomide (P) and dexamethasone (d), in patients with Relapsed/Refractory Multiple Myeloma (RRMM). Part B: To evaluate the feasibility of isatuximab administered from a fixed infusion volume in combination with Pd as assessed by occurrence of grade ≥3 infusion associated reactions (IAR). Secondary Objectives: * To evaluate the infusion duration (Part B). * To evaluate the safety profile of the combination with isatuximab administration from fixed volume (Part B). * To evaluate immunogenicity of SAR650984 in combination with Pd (Part A and B). * To evaluate the pharmacokinetics (PK) of SAR650984 and its effect on the PK of pomalidomide when administered in combination (Part A). * To describe the efficacy of the combination of SAR650984 with Pd in terms of overall response rate and clinical benefit rate based on International Myeloma Working Group (IMWG) defined response criteria and the duration of response (Part A and B). * To assess the relationship between clinical effects (adverse event \[AE\] and/or tumor response) and CD38 receptor density at baseline (Part A).
Detailed description
The study duration for an individual patient will include a screening period for inclusion of up to 21 days. The treatment period may continue until disease progression, unacceptable adverse reaction, or other reason for discontinuation. After study treatment discontinuation an end of treatment (EOT) visit will be done at approximately 30 days after last study treatment component administration to assess safety. If the last ADA sample is positive or inconclusive, additional ADA will be sampled 3 months later. No further ADA will be sampled, even if this 3-month sample is positive. Patients who discontinue treatment for reasons other than progression of disease will be followed every month until progression or initiation of subsequent therapy, for a maximum of one year, whichever comes first.
Interventions
Pharmaceutical form:solution for infusion Route of administration: intravenous
DRUGPomalidomide
Pharmaceutical form:capsules Route of administration: oral
DRUGDexamethasone
Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Patient 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. * Patient had received at least two previous therapies including lenalidomide and proteasome inhibitor and have demonstrated disease progression on therapy or after completion of the last therapy. * Patients 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).
Exclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status \>2. * Poor bone marrow reserve. * Poor organ function. * Known intolerance/hypersensitivity to IMiDs, dexamethasone, boron or mannitol, sucrose, histidine or polysorbate 80. * Any serious active disease (including clinically significant infection that is chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the Investigator, could interfere with the safety, the compliance with the study or with the interpretation of the results. * Any severe underlying medical conditions including presence of laboratory abnormalities, which could impair the ability to participate in the study or the interpretation of its results. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limiting Toxicities (DLTs) | Part A: Up to 4 weeks |
| Number of patients with adverse events and clinically significant changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling | Part A: Up to 30 days for patients experiencing progressive disease and up to one year or the initiation of a new line of treatment for patients leaving the study for reasons other than progressive disease |
| Incidence of grade ≥3 IARs according to the NCI-CTC version 4.03 grade scaling | Part B: Up to 8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Immune response: levels of human anti-human antibodies (ADA) | Part A: Up to approximately 8 months; Part B: Up to approximately 10 months |
| Duration of response - Time | Part A: Up to approximately 8 months; Part B: Up to approximately 10 months |
| Clinical Benefit rate | Part A: Up to approximately 8 months; Part B: Up to approximately 10 months |
| Overall response rate | Part A: Up to approximately 8 months; Part B: Up to approximately 10 months |
| Safety of isatuximab administration from fixed volume | Part B: Up to 30 days for patients experiencing progressive disease and up to one year or the initiation of a new line of treatment for patients leaving the study for reasons other than progressive disease |
| Relationship between clinical effect and CD38 receptor density | Part A: Up to approximately 8 months |
| Infusion duration | Part B: Up to approximately 10 months |
| Pharmacokinetics: Partial area under the serum concentration time curve (AUC) | Part A: Up to approximately 10 months |
| Pharmacokinetics: maximum observed concentration (Cmax) | Part A: Up to approximately 10 months |
Countries
United States
Outcome results
None listed