Bortezomib, Isatuximab, Cyclophosphamide and Dexamethasone Induction in Transplant-Eligible Multiple Myeloma Patients With Renal Insufficiency

NCT04240054 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00036788
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label phase II study with a safety lead-in phase.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Renal Insufficiency; Isatuximab

Outcome Measures

Primary Outcomes (1)

• The number of subjects who achieve very good partial response.

  This will be measured using the International Myeloma Working Group criteria.

  100 days following autologous stem cell transplant

Secondary Outcomes (2)

• The number of subjects who achieve complete response.

  100 days following autologous stem cell transplant.

• The number of subjects who achieve partial response.

  100 days following autologous stem cell transplant.

Study Arms (2)

Safety Lead-in Cohort A

EXPERIMENTAL

Six transplant-eligible multiple myeloma patients with renal impairment will be enrolled. Bortezomib (1.5 mg/m\^2) subcutaneous on days 1,8 and 15 Isatuximab (10 mg/kg) IV on days 1, 8, 15 and 22 Cyclophosphamide (250 mg/m\^2) IV on days 1, 8 and 15 Dexamethasone 20 mg PO or IV (10 mg if \>75 years) on days 1, 2, 8, 9,15,16, 22 and 23

Drug: Bortezomib; Drug: Isatuximab; Drug: Cyclophosphamide; Drug: Dexamethasone

Expansion Cohort A

EXPERIMENTAL

35 transplant-eligible multiple myeloma patients with renal impairment will be enrolled. Bortezomib (1.5 mg/m\^2)subcutaneous on days 1, 8 and 15 Isatuximab (10 mg/kg) IV on days 1, 8, 15 and 22 Cyclophosphamide (250 mg/m\^2) IV on days 1, 8 and 15 Dexamethasone 20 mg PO or IV (10 mg if \>75 years) on days 1, 2, 8, 9,15,16, 22 and 23

Drug: Bortezomib; Drug: Isatuximab; Drug: Cyclophosphamide; Drug: Dexamethasone

Interventions

Bortezomib DRUG

Bortezomib (1.5 mg/m\^2) subcutaneous on days 1, 8 and 15

Also known as: Velcade

Expansion Cohort A; Safety Lead-in Cohort A

Isatuximab DRUG

Isatuximab (10 mg/kg) IV on days 1, 8, 15 and 22

Also known as: SAR650984

Expansion Cohort A; Safety Lead-in Cohort A

Cyclophosphamide DRUG

Cyclophosphamide (250 mg/m\^2) IV on days 1, 8 and 15

Also known as: Cytoxan, Neosar, cytophosphane

Expansion Cohort A; Safety Lead-in Cohort A

Dexamethasone DRUG

Dexamethasone 20 mg PO or IV (10 mg if \>75 years) on days 1, 2, 8, 9, 15, 16, 22 and 23

Also known as: Baycadron, Decadron, DexPak, TaperDex, Zema-Pak, ZoDex, Zonacort

Expansion Cohort A; Safety Lead-in Cohort A

Eligibility Criteria

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

You may qualify if:

• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Male or female subjects ≥18 years.
• Patients must be eligible for high-dose therapy and autologous stem cell transplantation as per institutional guidelines.
• No prior multiple myeloma (MM) -directed therapy except for dexamethasone (up to 160 mg), bortezomib (up to 5.2 mg/m\^2) and/or cyclophosphamide up to 500 mg/m\^2 administered for management of acute manifestations of MM (hypercalcemia, renal impairment, pain) for no longer than four weeks prior to enrollment. If subject received any prior therapy, pretreatment parameters necessary for disease characterization and response assessment (at least one of the following: Serum protein electrophoresis (SPEP)/Immunofixation electrophoresis (IFE), 24-hour urine protein with urine protein electrophoresis (UPEP)/ IFE, serum free light chains and bone marrow procedure) must be available.
• Patients must have documented multiple myeloma as defined by the criteria below (a, b, and c):
• Monoclonal plasma cells in the bone marrow of ≥10% or presence of a biopsy proven plasmacytoma AND
• Evidence of organ damage or myeloma-defining events (MDE) that can be attributed to the underlying proliferative plasma cell disorder (at least one of the following):
• Hypercalcemia: corrected serum calcium \>1 mg/dL higher than the upper limit of normal (ULN) or \>11 mg/Dl.
• Anemia: hemoglobin value of \>2.0 g/dL below the lower limit of normal, or a hemoglobin value \<10.0 g/dL.
• Bone marrow plasma cells of \>60%. OR
• Involved/uninvolved light chain ratio ≥100 OR
• Renal insufficiency: eGFR \< 40 mL/min/1.73m\^2 (based on the Modification of Diet in Renal Disease MDRD formula). \[Cohort A subjects must meet this criterion.\] If the patient is enrolled in the renal impaired (RI) A cohort but Cycle 1 Day 1 labs do not meet RI definition, the patient will be considered RI (reconsent and rescreening are not required).
• Measurable disease as defined (at least one of the following):
• Serum M-protein level ≥0.5 g/dL; OR
• Urine M-protein level ≥200 mg/24 hours; OR

You may not qualify if:

• For renal impaired Cohort A subjects, any subject who requires immediate treatment for management of renal failure (including, but not limited to, dialysis). Such treatment is allowed once the patient becomes stable, based on investigator's discretion.
• Diagnosed or treated for malignancy other than multiple myeloma, except:
• Malignancy treated with curative intent and with no known active disease present for ≥3 years before enrollment or documentation that the malignancy required/requires no treatment at time of enrollment.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ (e.g., cervical, breast) with no evidence of disease.
• Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma.
• Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have untreated or active hepatitis C.
• Concurrent medical condition or disease (e.g., active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study. Specifically, any potential subject who is unsuitable for ASCT would be excluded from the study.
• Clinically significant cardiac disease, including:
• Myocardial infarction within six months before Cycle 1, Day 1, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
• Uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] Version 5 Grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities.
• Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) \>470 msec.
• Uncontrolled hypertension.
• Any of the following laboratory test results at the time of enrollment:
• Absolute neutrophil count \<1.0 × 109/L; no granulocyte colony stimulating factor (G-CSF) treatment in the past seven days are allowed.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Renal Insufficiency

Interventions

Bortezomib; isatuximab; Cyclophosphamide; Dexamethasone; Calcium Dobesilate

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; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Binod Dhakal, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: January 27, 2020
• Study Start: November 2, 2021
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)