A Phase 2 Study of Isatuximab in Combination With Pomalidomide and Dexamethasone in MM Patients Who Received One Prior Line of Therapy Containing Lenalidomide and a Proteasome Inhibitor

NCT05298683 | Unknown Phase 2

• 1 other identifier: EAE115
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 6

Brief Summary

This is an investigator-initiated (IIS), phase 2, prospective, open-label, multinational study, designed to be conducted in approximately 14 sites. Eligible patients will initially receive six 28-day cycles of isatuximab, pomalidomide, and low-dose dexamethasone. Following this phase: Patients who achieve ≥VGPR will be randomized in a 1:1 ratio to receive isatuximab, given either Q2W or once monthly, plus pomalidomide and low-dose dexamethasone. Patients with \<VGPR will continue treatment with isatuximab Q2W, pomalidomide, and low-dose dexamethasone. The study will last for 42 months (recruitment and follow-up period), starting from the date of the first patient in (FPI) to the date of the last patient last visit (LPLV). Core study procedures consist of baseline and post-baseline safety and disease evaluations, including physical examination, hematologic/clinical chemistry tests, radiologic assessments, bone marrow evaluations, and blood/urine M-protein assessments. Patients will be allowed to continue treatment until disease progression, death, unacceptable AEs, lost to follow-up, or consent withdrawal.

Conditions

Multiple Myeloma; Renal Impairment; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The primary endpoint is the ORR after six months of treatment with isatuximab in combination with pomalidomide, and low-dose dexamethasone. ORR is defined as the proportion of patients with stringent complete response (sCR), complete response (CR), VGPR, and partial response (PR), as assessed by the Investigator using the IMWG response criteria.

  After six months of treatment with isatuximab plus pomalidomide and low-dose dexamethasone

Secondary Outcomes (6)

• Progression-free Survival

  From study treatment initiation to progressive disease (PD), or initiation of further anti-myeloma treatment, or death, whichever occurs first. Maximum time period 42 months.

• Overall Survival (OS)

  From study treatment initiation to death. Maximum time period 42 months.

• Minimal Residual Response (MRD)

  Through study completion. Maximum time 42 months.

• Time to Response (TTR)

  From study treatment initiation to partial response (PR), or better. Maximum time period 42 months.

• Duration of Response (DoR)

  From time response is achieved to progressive disease (PD), or death, whichever comes first. Maximum time period 42 months.

Study Arms (1)

Single-Arm

EXPERIMENTAL

Eligible patients will initially receive six 28-day cycles of isatuximab, pomalidomide, and low-dose dexamethasone. Patients will be allowed to continue treatment until disease progression, death, unacceptable AEs, lost to follow-up, or consent withdrawal. Isatuximab will be given at a dose of 10 mg/kg QW by IV infusion. Pomalidomide will be given at 4 mg orally(PO) on Days 1-21 of each cycle. Dexamethasone will be given at 40 mg (20 mg for ≥75 years old) PO, or IV on days 1, 8, 15, and 22 in each cycle. Acetaminophen (paracetamol) will be given at 650-1000 mg PO 15-30 minutes (but no longer than 60 minutes) before isatuximab infusion. Ranitidine or equivalent will be given at 50 mg 15-30 minutes (but no longer than 60 minutes) before isatuximab infusion. Diphenhydramine or equivalent will be given at 25-50 mg 15-30 minutes (but no longer than 60 minutes) before isatuximab infusion.

Drug: Isatuximab; Drug: Pomalidomide; Drug: Dexamethasone; Drug: Acetaminophen (paracetamol); Drug: Ranitidine (or equivalent); Drug: Diphenhydramine (or equivalent)

Interventions

Isatuximab DRUG

Intravenous (IV) infusion. Dose regimen: Isatuximab will be given at a dose of 10 mg/kg QW by IV infusion on Days 1, 8, 15, and 22 in Cycle 1 and Days 1 and 15 in subsequent cycles. In patients with ≥VGPR who will be randomized to receive isatuximab once monthly from Cycle 7, isatuximab will be given on day 1 of each cycle.

Single-Arm

Pomalidomide DRUG

Route of administration: Oral (PO). Dose regimen: Pomalidomide will be given at 4 mg orally (PO) will be given on Days 1-21 of each cycle.

Single-Arm

Dexamethasone DRUG

Route of administration: PO or IV. Dose regimen: Dexamethasone will be given at 40 mg (20 mg for ≥75 years old) PO, or IV will be given on days 1, 8, 15, and 22 in each cycle.

Single-Arm

Acetaminophen (paracetamol) DRUG

Route of administration: PO. Dose regimen: Acetaminophen (paracetamol) will be given at 650-1000 mg PO 15-30 minutes (but no longer than 60 minutes) before isatuximab infusion

Single-Arm

Ranitidine (or equivalent) DRUG

Route of administration: IV. Dose regimen: Ranitidine or equivalent will be given at 50 mg 15-30 minutes (but no longer than 60 minutes) before isatuximab infusion.

Single-Arm

Diphenhydramine (or equivalent) DRUG

Route of administration: IV. Dose regimen: Diphenhydramine or equivalent will be given at 25-50 mg 15-30 minutes (but no longer than 60 minutes) before isatuximab infusion.

Single-Arm

Eligibility Criteria

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

You may qualify if:

• Patient has signed an informed consent form (ICF) indicating that he or she understands the purpose of the procedures required for the study and are willing to participate in the study. Patients must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF.
• Male or female patients aged 18 years or older at the time of the ICF signature.
• Patients who have received ONLY one prior line of anti-myeloma therapy, which included lenalidomide (at least 2 cycles, either alone or in combination) and a proteasome inhibitor (e.g. bortezomib, carfilzomib, ixazomib). Patients must have achieved at least a response of MR or better based on the investigator's determination of response as defined by the IMWG criteria.
• Note:
• An induction treatment followed by ASCT and consolidation/maintenance will be considered as one line of treatment.
• Patients with a documented diagnosis of MM and with current evidence of measurable disease defined as:
• Serum monoclonal protein (M-protein) level ≥0.5 g/dL, measured using serum protein electrophoresis (SPEP) and/or
• Urine M-protein level ≥200 mg/24 hours, measured using urine protein electrophoresis (UPEP), or
• Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
• Patients must have documented evidence of PD, based on the investigator's determination of response as defined by the IMWG criteria, on or after the last line of treatment.
• Adequate bone marrow and hepatic function as defined by ALL the laboratory criteria:
• Absolute Neutrophil Count (ANC) ≥1.0 x 109/L; GCSF administration is not allowed to reach this level
• Hemoglobin level ≥7.5 g/dL (≥4.65 mmol/L);
• Platelet count ≥75 x 109/L in patients in whom \<50% of bone marrow nucleated cells are plasma cells OR Platelet count ≥50 x 109/L in patients in whom ≥50% of bone marrow nucleated cells are plasma cells; \[transfusions are not permitted to reach this level\]
• Alanine aminotransferase (ALT) level ≤2.5 x ULN

You may not qualify if:

• Previous therapy with any anti-CD38 monoclonal antibody.
• Previous exposure to pomalidomide.
• Patient has received anti-myeloma treatment within two weeks or five pharmacokinetic half-lives of the treatment, whichever is longer, before Cycle 1, Day 1 (C1D1). The only exception is emergency use of a short course of corticosteroids (the equivalent of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment before C1D1.
• Previous allogeneic stem cell transplant or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1.
• History of malignancy (other than MM) within three years before C1D1 (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesions that in the opinion of the investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within three years).
• Clinical signs of meningeal involvement of MM.
• Clinically significant cardiac disease, including:
• Myocardial infarction within six months before C1D1, or unstable or uncontrolled condition (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
• Cardiac arrhythmia (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 3 or higher) or clinically significant electrocardiogram (ECG) abnormalities.
• Electrocardiogram showing a baseline QT interval as corrected QTc \>470 msec.
• Known:
• Active hepatitis A
• To be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Patients with resolved infection (i.e., patients who are positive for antibodies to hepatitis B core antigen \[antiHBc\] and/or antibodies to hepatitis B surface antigen \[antiHBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Patients with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• To be seropositive for hepatitis C (defined by a positive test for Hepatitis C virus (HCV) antibodies. A positive HCV antibody test should be confirmed by a HCV RNA test. EXCEPTION: Patients in the setting of a sustained virologic response, defined as aviremia at least 12 weeks after completion of antiviral therapy, are not excluded).
• Known to be seropositive for human immunodeficiency virus (defined by positive testing for human immunodeficiency virus (HIV) antibodies).

Sponsors & Collaborators

• Hellenic Society of Hematology: lead
• Sanofi: collaborator

Study Sites (6)

General Hospital of Athens "Evangelismos"

Athens, 106 76, Greece

Location

Anticancer Oncology Hospital of Athens "Agios Savvas"

Athens, 115 22, Greece

Location

General Hospital of Athens "Alexandra"

Athens, 115 28, Greece

Location

University General Hospital of Ioannina

Ioannina, 455 00, Greece

Location

University General Hospital of Patra

Pátrai, 265 04, Greece

Location

Anticancer Hospital of Thessaloniki "Theageneio"

Thessaloniki, 546 39, Greece

Location

MeSH Terms

Conditions

Multiple Myeloma; Renal Insufficiency; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases

Interventions

isatuximab; pomalidomide; Dexamethasone; Acetaminophen; Ranitidine; Diphenhydramine

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Evangelos Terpos, Prof

  Department of Clinical Therapeutics, School of Medicine, National Kapodistrian University of Athens (NKUA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Pagoni, Prof

CONTACT

+302107211806; info@eae.gr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2022
• First Posted: March 28, 2022
• Study Start: May 1, 2022
• Primary Completion: November 1, 2025
• Study Completion: January 1, 2026
• Last Updated: March 28, 2022

Record last verified: 2022-03

Locations

GR (6)