SAR650984, Pomalidomide and Dexamethasone in Combination in RRMM Patients

NCT02283775 | Completed Phase 1

• 2 other identifiers: TCD14079U1111-1155-7484
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 13

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).

Conditions

Plasma Cell Myeloma

Keywords

Anti-CD38 monoclonal antibody

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (9)

• Overall response rate

  Part A: Up to approximately 8 months; 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

• 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

Study Arms (1)

PomdeSAR

EXPERIMENTAL

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

Drug: Isatuximab SAR650984; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Isatuximab SAR650984 DRUG

Pharmaceutical form:solution for infusion Route of administration: intravenous

Also known as: Sarclisa

PomdeSAR

Pomalidomide DRUG

Pharmaceutical form:capsules Route of administration: oral

Also known as: Pomalyst

PomdeSAR

Dexamethasone DRUG

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

PomdeSAR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (13)

Investigational Site Number 840001

Scottsdale, Arizona, 85054, United States

Location

Investigational Site Number 840006

Duarte, California, 91010, United States

Location

Investigational Site Number 840018

New Haven, Connecticut, 06520-8017, United States

Location

Investigational Site Number 840011

Decatur, Illinois, 62526, United States

Location

Investigational Site Number 840004

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number 840104

Boston, Massachusetts, 2114, United States

Location

Investigational Site Number 840010

Chapel Hill, North Carolina, 27599, United States

Location

Investigational Site Number 840003

Charlotte, North Carolina, 28204, United States

Location

Investigational Site Number 840014

Canton, Ohio, 44718, United States

Location

Investigational Site Number 840016

Charleston, South Carolina, 29425, United States

Location

Investigational Site Number 840015

Salt Lake City, Utah, 84112-5550, United States

Location

Investigational Site Number 840005

Seattle, Washington, 98108, United States

Location

Investigational Site Number 840017

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (3)

• 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.

  PMID: 34050260 DERIVED

• 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.

  PMID: 33980831 DERIVED

• 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.

  PMID: 30862646 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2014
• First Posted: November 5, 2014
• Study Start: May 15, 2015
• Primary Completion: May 26, 2021
• Study Completion: May 26, 2021
• Last Updated: July 9, 2021

Record last verified: 2021-07

Locations

US (13)