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

Phase 1

Conditions: Multiple myeloma patients who received one prior line of therapy containing Lenalidomide and a Proteasome Inhibitor.
Therapeutic area: Diseases [C] - Cancer [C04]
MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2021-004917-38-GR

Lead Sponsor: Hellenic Society of Hematology (EAE)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 108

Inclusion Criteria

1. Patient has signed an informed consent form (ICF) indicating that he or she understands the purpose of the procedures required for the study and is 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.
2. Male or female patients aged 18 years or older at the time of the ICF signature.
3. 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 1:
An induction treatment followed by ASCT and consolidation/maintenance will be considered as one line of treatment.
Note 2: The number of prior lines will be defined according to the guidelines for
determination of the number of prior lines of therapy in multiple myeloma (Appendix
F).
4. 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.
5. 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.
6. 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
-Aspartate aminotransferase (AST) level =2.5 x ULN
-Total bilirubin level =1.5 x ULN (except for Gilbert Syndrome: direct bilirubin =1.5 x ULN)
-Creatinine clearance =30 mL/min; calculated using Cockcroft Gault
-Serum calcium corrected for albumin =14.0 mg/dL (=3.5 mmol/L), or free ionized calcium = 6.5 mg/dL (=1.6 mmol/L)
7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) =2 (see Appendix B).
8. For patients experiencing toxicities resulting from previous therapy, the toxicities must be resolved or stabilized to = Grade 1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 73

Exclusion Criteria

1. Previous therapy with any anti-CD38 monoclonal antibody within 12 months before C1D1.
2. Previous exposure to pomalidomide.
3. 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. 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.
4. Previous allogeneic stem cell transplant or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1.
5. History of malignancy (other than MM) within three years before C1D1.
6. Clinical signs of meningeal involvement of MM.
7. Clinically significant cardiac disease, including:
a) 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).
b) Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 or higher) or clinically significant electrocardiogram (ECG) abnormalities.
c) Electrocardiogram showing a baseline QT interval as corrected QTc >470 msec.
8. Known:
a) Active hepatitis A
b) To be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Patients with resolved infection 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.
c) To be seropositive for hepatitis C.
9. Known to be seropositive for human immunodeficiency virus (defined by positive testing for human immunodeficiency virus (HIV) antibodies).
10. Gastrointestinal disease that may significantly alter the absorption of pomalidomide.
11. Patient has plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström’s macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.
12. Any concurrent medical or psychiatric condition or disease that is likely to interfere with the study procedures or results or that, in the opinion of the investigator, would constitute a hazard for participating in this study.
13. Ongoing =Grade 2 peripheral neuropathy.
14. Patient had =Grade 3 rash during prior therapy.
15. Patient has had major surgery within two weeks before C1D1, or has not fully recovered from an earlier surgery, or has a surgery planned during the time the patient is expected to participate in the study or within two weeks after the last dose of study drug administration. Note: patients with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery.
16. Patient has known allergies, hypersensitivity, or intolerance to any of the study drugs, monoclonal antibodies, human proteins, or their excipients (refer to isatuximab IB) or known sensitivity to mammalian-derived products.
17. Patient was vaccinated with live vaccines within four weeks prior to C1D1.
18. Pregnant or nursing women.
19. a. Females of childbearing potential (FCBP) unwilling to prevent pregnancy with the use of two reliable methods