Clinical trial NCT02283775: SAR650984, Pomalidomide and Dexamethasone in Combination in RRMM Patients
Official title: A Phase 1b Study of SAR650984 (Isatuximab) in Combination With Pomalidomide and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Plasma Cell Myeloma
Keywords: Anti-CD38 monoclonal antibody
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2014-11-05
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs)
timeFrame: Part A: Up to 4 weeks
measure: 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
timeFrame: 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
measure: Incidence of grade ≥3 IARs according to the NCI-CTC version 4.03 grade scaling
timeFrame: Part B: Up to 8 weeks
Secondary outcomes:
measure: Overall response rate
timeFrame: Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
measure: Pharmacokinetics: Partial area under the serum concentration time curve (AUC)
timeFrame: Part A: Up to approximately 10 months
measure: Pharmacokinetics: maximum observed concentration (Cmax)
timeFrame: Part A: Up to approximately 10 months
measure: Immune response: levels of human anti-human antibodies (ADA)
timeFrame: Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
measure: Duration of response - Time
timeFrame: Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
measure: Clinical Benefit rate
timeFrame: Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
measure: Infusion duration
timeFrame: Part B: Up to approximately 10 months
measure: Safety of isatuximab administration from fixed volume
timeFrame: 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
measure: Relationship between clinical effect and CD38 receptor density
timeFrame: Part A: Up to approximately 8 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Investigational Site Number 840001
state: Arizona
city: Duarte
country: United States
facility: Investigational Site Number 840006
state: California
city: New Haven
country: United States
facility: Investigational Site Number 840018
state: Connecticut
city: Decatur
country: United States
facility: Investigational Site Number 840011
state: Illinois
city: Boston
country: United States
facility: Investigational Site Number 840004
state: Massachusetts
city: Boston
country: United States
facility: Investigational Site Number 840104
state: Massachusetts
city: Chapel Hill
country: United States
facility: Investigational Site Number 840010
state: North Carolina
city: Charlotte
country: United States
facility: Investigational Site Number 840003
state: North Carolina
city: Canton
country: United States
facility: Investigational Site Number 840014
state: Ohio
city: Charleston
country: United States
facility: Investigational Site Number 840016
state: South Carolina
city: Salt Lake City
country: United States
facility: Investigational Site Number 840015
state: Utah
city: Seattle
country: United States
facility: Investigational Site Number 840005
state: Washington
city: Milwaukee
country: United States
facility: Investigational Site Number 840017
state: Wisconsin
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Usmani SZ, Karanes C, Bensinger WI, D'Souza A, Raje N, Tuchman SA, Sborov D, Laubach JP, Bianchi G, Kanagavel D, Saleem R, Dubin F, Campana F, Richardson PG. Final results of a phase 1b study of isatuximab short-duration fixed-volume infusion combination therapy for relapsed/refractory multiple myeloma. Leukemia. 2021 Dec;35(12):3526-3533. doi: 10.1038/s41375-021-01262-w. Epub 2021 May 28.
citation: Mikhael J, Belhadj-Merzoug K, Hulin C, Vincent L, Moreau P, Gasparetto C, Pour L, Spicka I, Vij R, Zonder J, Atanackovic D, Gabrail N, Martin TG, Perrot A, Bensfia S, Weng Q, Brillac C, Semiond D, Mace S, Corzo KP, Leleu X. A phase 2 study of isatuximab monotherapy in patients with multiple myeloma who are refractory to daratumumab. Blood Cancer J. 2021 May 12;11(5):89. doi: 10.1038/s41408-021-00478-4. No abstract available.
citation: Mikhael J, Richardson P, Usmani SZ, Raje N, Bensinger W, Karanes C, Campana F, Kanagavel D, Dubin F, Liu Q, Semiond D, Anderson K. A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. Blood. 2019 Jul 11;134(2):123-133. doi: 10.1182/blood-2019-02-895193. Epub 2019 Mar 12.