SAR650984, Pomalidomide and Dexamethasone in Combination in RRMM Patients

NCT ID: NCT02283775

Last Updated: 2021-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-15
• Study Completion Date: 2021-05-26

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.

Conditions

Plasma Cell Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PomdeSAR

Part A: Isatuximab (escalating dose) on Day 1, 8, 15, and 22, then Day 1 and 15 + pomalidomide 4 mg on Day 1 to 21 + dexamethasone 40 mg (20 mg in patients of 75 years or older) on Day 1, 8, 15, 22 in 28-day cycles up to disease progression

Part B: Isatuximab 10 mg/kg on Day 1, 8, 15, and 22, then Day 1 and 15 + pomalidomide 4 mg on Day 1 to 21 + dexamethasone 40 mg (20 mg in patients of 75 years or older) on Day 1, 8, 15, 22 in 28-day cycles up to disease progression

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form:solution for infusion Route of administration: intravenous

Pomalidomide

Intervention Type: DRUG

Pharmaceutical form:capsules Route of administration: oral

Dexamethasone

Intervention Type: DRUG

Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous

Interventions

Isatuximab SAR650984

Pharmaceutical form:solution for infusion Route of administration: intravenous

Intervention Type: DRUG

Pomalidomide

Pharmaceutical form:capsules Route of administration: oral

Intervention Type: DRUG

Dexamethasone

Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous

Intervention Type: DRUG

Other Intervention Names

Sarclisa; Pomalyst

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840001

Scottsdale, Arizona, United States

Investigational Site Number 840006

Duarte, California, United States

Investigational Site Number 840018

New Haven, Connecticut, United States

Investigational Site Number 840011

Decatur, Illinois, United States

Investigational Site Number 840004

Boston, Massachusetts, United States

Investigational Site Number 840104

Boston, Massachusetts, United States

Investigational Site Number 840010

Chapel Hill, North Carolina, United States

Investigational Site Number 840003

Charlotte, North Carolina, United States

Investigational Site Number 840014

Canton, Ohio, United States

Investigational Site Number 840016

Charleston, South Carolina, United States

Investigational Site Number 840015

Salt Lake City, Utah, United States

Investigational Site Number 840005

Seattle, Washington, United States

Investigational Site Number 840017

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34050260 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33980831 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30862646 (View on PubMed)

Other Identifiers

U1111-1155-7484

Identifier Type: OTHER

Identifier Source: secondary_id

TCD14079

Identifier Type: -

Identifier Source: org_study_id