RECRUITING

Isatuximab in Combination With Novel Agents in RRMM - Master Protocol

Conditions

Plasma Cell Myeloma Refractory anti-CD38 monoclonal antibody master protocol combination therapy CD38 resistance interleukin 2 ROCK2 inhibitor anti-CD47 agent

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this umbrella study is to evaluate isatuximab when combined with novel agents with or without dexamethasone in participants with relapsed or refractory myeloma. Substudy 01 is the control Substudy. Substudies 02, 03, and 06 are controlled experimental substudies. Substudies 04 and 05 are independent experimental substudies.

Official Title

Phase 1-2 UMBRELLA Trial Evaluating Isatuximab With or Without Dexamethasone in Combination With Novel Agents Compared to Isatuximab With Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma (RRMM) - Master Protocol

Quick Facts

Study Start:2021-01-25

Study Completion:2028-03-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04643002

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Participant must be 18 years of age inclusive or older. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Participants with relapsed or refractory MM who have received at least 2 prior lines of therapy for MM, including PIs and IMiDs (eg, Induction regimen with autologous stem cell transplant followed by maintenance is considered one line). * RRMM with measurable disease: * Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or * Urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or * Serum free light chain (sFLC) MM without measurable M protein in serum or urine per previous criteria (serum Ig free light chain ≥10 mg/dL and abnormal serum Ig kappa lambda free light chain ratio \<0.26 or \>1.65). * Men or woman or childbearing potential should agree to use contraception. * Substudy 01, 06: Anti-CD38 therapy naïve or prior exposure to such drugs with a wash out of at least 12 months after the last dose. "Exposure" is defined as at least 2 cycles of therapy. * Substudies 02, 03: Anti-CD38 therapy naïve or prior exposure to such drugs without being refractory but with a wash out of at least 6 months after the last dose. "Refractory" is defined as progressing within 60 days of last dose of anti-CD38 targeting therapy. * Substudy 04: Anti-CD38 and anti-B cell maturation antigen (BCMA) therapy (if available) prior exposed participants with RRMM. For anti-CD38, "Exposure" is defined as at least 2 cycles of therapy. For anti-BCMA therapy if available, exposure is defined by at least 2 cycles of therapy. * Substudy 05: Participants with RRMM with at least 2 cycles of prior exposure to anti-CD38 therapy. For participants to whom BCMA targeted therapy is available (ie, approved in their region and can be reimbursed), at least 2 cycles of prior exposure to a BCMA targeted agent is mandatory.	* Primary systemic amyloid light chain amyloidosis, plasma cell leukemia, monoclonal gammopathy of undetermined significance, or smoldering myeloma. * Uncontrolled infection within 14 days prior to first study intervention administration. * Clinically significant cardiac (including valvular) or vascular disease within 3 months prior to first study intervention administration., eg, myocardial infarction, unstable angina, coronary (eg, coronary artery bypass graft, percutaneous coronary intervention) or peripheral artery revascularization, left ventricular ejection fraction \<40%, heart failure New York Heart Association Classes III and IV, stroke, transient ischemic attack, pulmonary embolism, other thromboembolic event, or cardiac arrhythmia (Grade 3 or higher by NCI CTCAE Version 5.0). * Known acquired immunodeficiency syndrome-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A. * Uncontrolled or active hepatitis B virus (HBV) infection. * Active hepatitis C virus (HCV) infection. * Any of the following within 3 months prior to first study intervention administration: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease. * Second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma, unless they are successfully treated with curative intent for more than 3 years before first study intervention administration. * Any anti-MM drug treatment within 14 days before first study intervention administration, including dexamethasone. * Participants with a contraindication to treatment. * Vaccination with a live vaccine 4 weeks before the start of the study. * Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted. * Hemoglobin \<8 g/dL. * Platelets \<50 × 10\^9/L. * Absolute neutrophil count \<1.0 × 10\^9/L. * Creatinine clearance \<30 mL/min/1.73m2. * Total bilirubin \>1.5 × ULN, except for known Gilbert syndrome in which direct bilirubin should be ≤2.5 × ULN. * Aspartate aminotransferase and/or alanine aminotransferase \>3 × ULN. * Patients with grade 3 or 4 hypercalcemia. * History of resected/ablated basal or squamous cell carcinoma (SCC) of the skin or carcinoma in situ of the cervix, or other local tumors, even if considered cured by local treatment. * Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior to the first dose of SAR439459. * Prothrombin time or INR \>1.5 × upper limit of normal (ULN). * Current corneal epithelial disease except mild punctate keratopathy. * Patients who have received prior therapy with belantamab mafodotin. * Central nervous system or leptomeningeal disease. * Medical history of seizure. * Participants currently receiving hepatically metabolized narrow therapeutic index drugs (eg, digoxin, warfarin) if cannot be closely monitored. * Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs), except controlled by replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc). The following are not exclusionary: vitiligo, childhood asthma that has resolved, psoriasis that does not require systemic treatment. * Prior allogeneic hematopoietic stem cell transplant (allo-HSCT). * History of active autoimmune disorders. * History of autoimmune hemolytic anemia or autoimmune. thrombocytopenia. * Active graft versus host disease (GVHD) or ongoing immunosuppression for GVHD. * Prior allogenic hematopoietic stem cell transplant (allo-HSCT). * Patient with chronic active EBV infection. * Patients with known history of HLH. * Hemoglobin \< 9 g/dL. * Prior therapy with any anti-CD47 or anti signal regulatory protein alpha agent.

Inclusion Criteria

Exclusion Criteria

* Participant must be 18 years of age inclusive or older.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* Participants with relapsed or refractory MM who have received at least 2 prior lines of therapy for MM, including PIs and IMiDs (eg, Induction regimen with autologous stem cell transplant followed by maintenance is considered one line).
* RRMM with measurable disease:
* Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or
* Urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or
* Serum free light chain (sFLC) MM without measurable M protein in serum or urine per previous criteria (serum Ig free light chain ≥10 mg/dL and abnormal serum Ig kappa lambda free light chain ratio \<0.26 or \>1.65).
* Men or woman or childbearing potential should agree to use contraception.
* Substudy 01, 06: Anti-CD38 therapy naïve or prior exposure to such drugs with a wash out of at least 12 months after the last dose. "Exposure" is defined as at least 2 cycles of therapy.
* Substudies 02, 03: Anti-CD38 therapy naïve or prior exposure to such drugs without being refractory but with a wash out of at least 6 months after the last dose. "Refractory" is defined as progressing within 60 days of last dose of anti-CD38 targeting therapy.
* Substudy 04: Anti-CD38 and anti-B cell maturation antigen (BCMA) therapy (if available) prior exposed participants with RRMM. For anti-CD38, "Exposure" is defined as at least 2 cycles of therapy. For anti-BCMA therapy if available, exposure is defined by at least 2 cycles of therapy.
* Substudy 05: Participants with RRMM with at least 2 cycles of prior exposure to anti-CD38 therapy. For participants to whom BCMA targeted therapy is available (ie, approved in their region and can be reimbursed), at least 2 cycles of prior exposure to a BCMA targeted agent is mandatory.

* Primary systemic amyloid light chain amyloidosis, plasma cell leukemia, monoclonal gammopathy of undetermined significance, or smoldering myeloma.
* Uncontrolled infection within 14 days prior to first study intervention administration.
* Clinically significant cardiac (including valvular) or vascular disease within 3 months prior to first study intervention administration., eg, myocardial infarction, unstable angina, coronary (eg, coronary artery bypass graft, percutaneous coronary intervention) or peripheral artery revascularization, left ventricular ejection fraction \<40%, heart failure New York Heart Association Classes III and IV, stroke, transient ischemic attack, pulmonary embolism, other thromboembolic event, or cardiac arrhythmia (Grade 3 or higher by NCI CTCAE Version 5.0).
* Known acquired immunodeficiency syndrome-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A.
* Uncontrolled or active hepatitis B virus (HBV) infection.
* Active hepatitis C virus (HCV) infection.
* Any of the following within 3 months prior to first study intervention administration: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease.
* Second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma, unless they are successfully treated with curative intent for more than 3 years before first study intervention administration.
* Any anti-MM drug treatment within 14 days before first study intervention administration, including dexamethasone.
* Participants with a contraindication to treatment.
* Vaccination with a live vaccine 4 weeks before the start of the study.
* Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
* Hemoglobin \<8 g/dL.
* Platelets \<50 × 10\^9/L.
* Absolute neutrophil count \<1.0 × 10\^9/L.
* Creatinine clearance \<30 mL/min/1.73m2.
* Total bilirubin \>1.5 × ULN, except for known Gilbert syndrome in which direct bilirubin should be ≤2.5 × ULN.
* Aspartate aminotransferase and/or alanine aminotransferase \>3 × ULN.
* Patients with grade 3 or 4 hypercalcemia.
* History of resected/ablated basal or squamous cell carcinoma (SCC) of the skin or carcinoma in situ of the cervix, or other local tumors, even if considered cured by local treatment.
* Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior to the first dose of SAR439459.
* Prothrombin time or INR \>1.5 × upper limit of normal (ULN).
* Current corneal epithelial disease except mild punctate keratopathy.
* Patients who have received prior therapy with belantamab mafodotin.
* Central nervous system or leptomeningeal disease.
* Medical history of seizure.
* Participants currently receiving hepatically metabolized narrow therapeutic index drugs (eg, digoxin, warfarin) if cannot be closely monitored.
* Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs), except controlled by replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc). The following are not exclusionary: vitiligo, childhood asthma that has resolved, psoriasis that does not require systemic treatment.
* Prior allogeneic hematopoietic stem cell transplant (allo-HSCT).
* History of active autoimmune disorders.
* History of autoimmune hemolytic anemia or autoimmune. thrombocytopenia.
* Active graft versus host disease (GVHD) or ongoing immunosuppression for GVHD.
* Prior allogenic hematopoietic stem cell transplant (allo-HSCT).
* Patient with chronic active EBV infection.
* Patients with known history of HLH.
* Hemoglobin \< 9 g/dL.
* Prior therapy with any anti-CD47 or anti signal regulatory protein alpha agent.

Contacts and Locations

Study Contact

Trial Transparency email recommended (Toll free number for US & Canada)

CONTACT

800-633-1610

Contact-US@sanofi.com

Principal Investigator

Clinical Sciences & Operations

STUDY_DIRECTOR

Sanofi

Study Locations (Sites)

University of Illinois Site Number : 8400007

Chicago, Illinois, 60612

United States

University of Michigan Site Number : 8400004

Ann Arbor, Michigan, 48109

United States

Roswell Park Cancer Institute Site Number : 8400008

Buffalo, New York, 14263-0001

United States

Collaborators and Investigators

Sponsor: Sanofi

Clinical Sciences & Operations, STUDY_DIRECTOR, Sanofi

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-01-25

Study Completion Date2028-03-31

Study Record Updates

Study Start Date2021-01-25

Study Completion Date2028-03-31

Terms related to this study

Keywords Provided by Researchers

anti-CD38 monoclonal antibody
master protocol
combination therapy
CD38 resistance
interleukin 2
ROCK2 inhibitor
anti-CD47 agent

Additional Relevant MeSH Terms

Plasma Cell Myeloma Refractory