SAR650984, Pomalidomide and Dexamethasone in Combination in RRMM Patients (PomdeSAR)

• ClinicalTrials.gov Identifier: NCT02283775
• Recruitment Status: Completed
• First Posted: November 5, 2014
• Last Update Posted: July 9, 2021
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Plasma Cell Myeloma	Drug: Isatuximab SAR650984; Drug: Pomalidomide; Drug: Dexamethasone	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b Study of SAR650984 (Isatuximab) in Combination With Pomalidomide and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma
• Actual Study Start Date: May 15, 2015
• Actual Primary Completion Date: May 26, 2021
• Actual Study Completion Date: May 26, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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

Drug: Isatuximab SAR650984; Pharmaceutical form:solution for infusion Route of administration: intravenous; Other Name: Sarclisa; Drug: Pomalidomide; Pharmaceutical form:capsules Route of administration: oral; Other Name: Pomalyst; Drug: Dexamethasone; Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous

Outcome Measures

Primary Outcome Measures :

1. Dose Limiting Toxicities (DLTs) [ Time Frame: Part A: Up to 4 weeks ]
2. 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 [ Time Frame: 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 ]
3. Incidence of grade ≥3 IARs according to the NCI-CTC version 4.03 grade scaling [ Time Frame: Part B: Up to 8 weeks ]

Secondary Outcome Measures :

1. Overall response rate [ Time Frame: Part A: Up to approximately 8 months; Part B: Up to approximately 10 months ]
2. Pharmacokinetics: Partial area under the serum concentration time curve (AUC) [ Time Frame: Part A: Up to approximately 10 months ]
3. Pharmacokinetics: maximum observed concentration (Cmax) [ Time Frame: Part A: Up to approximately 10 months ]
4. Immune response: levels of human anti-human antibodies (ADA) [ Time Frame: Part A: Up to approximately 8 months; Part B: Up to approximately 10 months ]
5. Duration of response - Time [ Time Frame: Part A: Up to approximately 8 months; Part B: Up to approximately 10 months ]
6. Clinical Benefit rate [ Time Frame: Part A: Up to approximately 8 months; Part B: Up to approximately 10 months ]
7. Infusion duration [ Time Frame: Part B: Up to approximately 10 months ]
8. Safety of isatuximab administration from fixed volume [ Time Frame: 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 ]
9. Relationship between clinical effect and CD38 receptor density [ Time Frame: Part A: Up to approximately 8 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Arizona

Investigational Site Number 840001

Scottsdale, Arizona, United States, 85054

United States, California

Investigational Site Number 840006

Duarte, California, United States, 91010

United States, Connecticut

Investigational Site Number 840018

New Haven, Connecticut, United States, 06520-8017

United States, Illinois

Investigational Site Number 840011

Decatur, Illinois, United States, 62526

United States, Massachusetts

Investigational Site Number 840004

Boston, Massachusetts, United States, 02115

Investigational Site Number 840104

Boston, Massachusetts, United States, 2114

United States, North Carolina

Investigational Site Number 840010

Chapel Hill, North Carolina, United States, 27599

Investigational Site Number 840003

Charlotte, North Carolina, United States, 28204

United States, Ohio

Investigational Site Number 840014

Canton, Ohio, United States, 44718

United States, South Carolina

Investigational Site Number 840016

Charleston, South Carolina, United States, 29425

United States, Utah

Investigational Site Number 840015

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

United States, Washington

Investigational Site Number 840005

Seattle, Washington, United States, 98108

United States, Wisconsin

Investigational Site Number 840017

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02283775
• Other Study ID Numbers: TCD14079; U1111-1155-7484 ( Other Identifier: UTN )
• First Posted: November 5, 2014
• Last Update Posted: July 9, 2021
• Last Verified: July 2021

Keywords provided by Sanofi:

Anti-CD38 monoclonal antibody

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Dexamethasone; Pomalidomide; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents