Ixazomib-pomalidomide-dexamethasone as Second or Third-line Combination Treatment for Patients With Relapsed and Refractory Multiple Myeloma Previously Treated With Daratumumab, Lenalidomide and Bortezomib

NCT04790474 | Active Not Recruiting Phase 2

• 1 other identifier: 0776-19-TLV
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 7

Brief Summary

Adult patients with a confirmed diagnosis of symptomatic and relapsed and/or refractory MM, after receiving bortezomib, lenalidomide and daratumumab during first and second lines, will be eligible to be enrolled in this study. During the first three treatment cycles, patients will be seen twice (Days 1 and 15 of the cycle). Starting from cycle 4 and on, patients will be assessed once per cycle (Day 1), until disease progression, for disease response and progression according to the International Myeloma Working Group (IMWG) criteria. After progression, all patients will be followed for survival; for this purpose, patients will be contacted every 12 weeks until death or termination of the study by the Sponsor. Patients may continue to receive treatment for 24 months or until disease progression (PD) or unacceptable toxicity, the earlier of the three. Dose modifications may be made based on toxicities. Patients who complete study therapy will continue to receive treatment per standard of care.

Conditions

Multiple Myeloma in Relapse; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival-PFS

  The time from first dose to the date of the first documented tumor progression or death due to any cause

  Up to 2 years from last patient enrollment

Secondary Outcomes (4)

• Objective Response Rate-ORR

  Up to 2 years from last patient enrollment

• Overall Survival-OS

  Up to 2 years from last patient enrollment

• Time To Response-TTR

  Up to 2 years from last patient enrollment

• Duration of Response-DOR-

  Up to 2 years from last patient enrollment

Other Outcomes (1)

• Optional Exploratory Analysis- RNA sequencing

  Up to 2 years from last patient enrollment

Study Arms (1)

ixazomib-pomalidomide-dexamethasone as second or third-line combination treatment

EXPERIMENTAL

Prospective study of ixazomib-pomalidomide-dexamethasone as second or third-line combination treatment for patients with relapsed and refractory multiple myeloma (RRMM) previously treated with daratumumab, lenalidomide and bortezomib

Drug: ixazomib-pomalidomide-dexamethasone

Interventions

ixazomib-pomalidomide-dexamethasone DRUG

Cycles 1-3: during each 21-day cycle: * ixazomib 3 mg on Days 1, 4, 8 and 11 * pomalidomide 4 mg on Days 1 through 14 * dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16 Cycle 4 and consequently: during each 28-day cycle: * ixazomib 4 mg on Days 1, 8 and 15 * pomalidomide 4 mg on Days 1 through 21 * dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16, 22 and 23

ixazomib-pomalidomide-dexamethasone as second or third-line combination treatment

Eligibility Criteria

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

You may qualify if:

• Male or female patients, 18 years of age or older.
• Multiple myeloma diagnosed according to standard IMWG criteria
• Patients must have measurable disease defined by at least one of the following five measurements:
• Serum M-protein 1 g/dL (10 g/L).
• Urine M-protein 200 mg/24 hours.
• Serum free light chain assay: involved free light chain level at least 100 mg/L), provided that the serum free light chain ratio is abnormal.
• A biopsy proven evaluable plasmacytoma
• Bone marrow plasmacytosis \> 30% of total marrow cells
• Patients received one or two prior lines of therapy which must have included bortezomib, lenalidomide-and daratumumab.
• Patients must meet the following clinical laboratory criteria:
• Absolute neutrophil count (ANC) ≥1,000/mm3 and platelet count≥75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days of enrollment.
• Total bilirubin ≤1.5 the upper limit of the normal range (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 ULN.
• Calculated creatinine clearance ≥15 mL/min note: Patients with creatinine clearance of 15-50 mL/min will receive pomalidomide at a reduced dose (3 mg), which may subsequently be increased if well tolerated.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

You may not qualify if:

• Patient underwent an allogeneic transplantation
• Female patients who are lactating or pregnant.
• Major surgery within 14 days before enrollment.
• Central nervous system involvement
• Concomitant use of any other antineoplastic treatment with activity against MM (with the exception of ≤40 mg Dexamethasone per day or equivalent for no longer than 4 days).
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment
• Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
• Anti-myeloma therapy as follows prior to screening bone marrow aspiration:
• Targeted therapy, epigenetic therapy, within 14 days or at least 5 half-lives,whichever is less;
• Monoclonal antibody treatment for multiple myeloma within 21 days;
• Cytotoxic therapy within 14 days;
• Proteasome inhibitor therapy within 14 days;
• Immunomodulatory agent therapy within 7 days.
• Radiotherapy within 14 days (with the exception of radiotherapy for spinal cord compression or for pain control that should be discussed and approved by the sponsor- investigator prior to study enrollment). However, if the radiation portal covered ≤5% of the bone marrow reserve, the subject is eligible irrespective of the end date of radiotherapy.

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead

Study Sites (7)

Emek Medical Center

Afula, 18101, Israel

Location

Rambam Medical Center

Haifa, Israel

Location

Hadassah Ein-Kerem Medical Center

Jerusalem, Israel

Location

Shearei Zedek Medical Center

Jerusalem, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Sheba Tel Hashomer

Ramat Gan, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

MeSH Terms

Conditions

Multiple Myeloma

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

Study Officials

• Yael Cohen, MD

  Tel-Aviv Sourasky Medical Center

  PRINCIPAL INVESTIGATOR

• Noa Lavi, MD

  Rambam Health Care Campus

  PRINCIPAL INVESTIGATOR

• Moshe Gat, MD

  Hadassah Ein-Keerm Medical Center

  PRINCIPAL INVESTIGATOR

• Iuliana Vaxman, MD

  Rabin Medical Center

  PRINCIPAL INVESTIGATOR

• Hila Magen, MD

  Shiba Tel Hashomer Medical Center

  PRINCIPAL INVESTIGATOR

• Chezi Ganzel, MD

  Shearei Zedek Medical Center

  PRINCIPAL INVESTIGATOR

• Evgeni Chubar, MD

  Emek Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 7, 2021
• First Posted: March 10, 2021
• Study Start: March 25, 2021
• Primary Completion: March 1, 2026
• Study Completion (Estimated): September 1, 2029
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IL (7)