SAR650984, Pomalidomide and Dexamethasone in Combination in RRMM Patients

Plasma Cell Myeloma Clinical Trial

— PomdeSAR  

Official title:

A Phase 1b Study of SAR650984 (Isatuximab) in Combination With Pomalidomide and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02283775
• Other study ID #: TCD14079
• Secondary ID: U1111-1155-7484
• Status: Completed
• Phase: Phase 1
• Start date: May 15, 2015
• Est. completion date: May 26, 2021

Study information

• Verified date: July 2021
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: May 26, 2021
• Est. primary completion date: May 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Plasma Cell Myeloma

Intervention

Drug:
• Isatuximab SAR650984
Pharmaceutical form:solution for infusion Route of administration: intravenous
• Pomalidomide
Pharmaceutical form:capsules Route of administration: oral
• Dexamethasone
Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous

Locations

Country	Name	City	State
United States	Investigational Site Number 840004	Boston	Massachusetts
United States	Investigational Site Number 840104	Boston	Massachusetts
United States	Investigational Site Number 840014	Canton	Ohio
United States	Investigational Site Number 840010	Chapel Hill	North Carolina
United States	Investigational Site Number 840016	Charleston	South Carolina
United States	Investigational Site Number 840003	Charlotte	North Carolina
United States	Investigational Site Number 840011	Decatur	Illinois
United States	Investigational Site Number 840006	Duarte	California
United States	Investigational Site Number 840017	Milwaukee	Wisconsin
United States	Investigational Site Number 840018	New Haven	Connecticut
United States	Investigational Site Number 840015	Salt Lake City	Utah
United States	Investigational Site Number 840001	Scottsdale	Arizona
United States	Investigational Site Number 840005	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities (DLTs)		Part A: Up to 4 weeks
Primary	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
Primary	Incidence of grade =3 IARs according to the NCI-CTC version 4.03 grade scaling		Part B: Up to 8 weeks
Secondary	Overall response rate		Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
Secondary	Pharmacokinetics: Partial area under the serum concentration time curve (AUC)		Part A: Up to approximately 10 months
Secondary	Pharmacokinetics: maximum observed concentration (Cmax)		Part A: Up to approximately 10 months
Secondary	Immune response: levels of human anti-human antibodies (ADA)		Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
Secondary	Duration of response - Time		Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
Secondary	Clinical Benefit rate		Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
Secondary	Infusion duration		Part B: Up to approximately 10 months
Secondary	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
Secondary	Relationship between clinical effect and CD38 receptor density		Part A: Up to approximately 8 months