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

A Multisite, Phase II Study of Bortezomib, Isatuximab, Cyclophosphamide and Dexamethasone (VICD) Induction in Transplant-Eligible Multiple Myeloma Patients With Renal Insufficiency

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

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bortezomib; Drug: Isatuximab; Drug: Cyclophosphamide; Drug: Dexamethasone

Detailed Description

The study hypothesis is that the isatuximab plus bortezomib, cyclophosphamide and dexamethasone (VCD) combination is safe and highly effective even in those with renal insufficiency (RI) from myeloma. In this study, we seek to improve the efficacy of VCD by adding isatuximab in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant (ASCT) irrespective of renal function.

The primary objective is to determine if the addition of isatuximab to VCD will increase the proportion of subjects achieving very good partial response (VGPR), as defined by the International Myeloma Working Group (IMWG) criteria and by the time of completion of post-ASCT consolidation treatment.

• Study Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Medical College of Wisconsin Cancer Center Clinical Trials Office; Phone Number: 8900 866-680-0505; Email: cccto@mcw.edu

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Hospital & the Medical College of Wisconsin
      • Contact: Medical College of Wisconsin Cancer Center Clinical Trials Office; Phone Number: 8900 866-680-0505; Email: cccto@mcw.edu
      • Principal Investigator: Binod Dhakal, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
2. Male or female subjects ≥18 years.
3. Patients must be eligible for high-dose therapy and autologous stem cell transplantation as per institutional guidelines.
4. 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.

5. Patients must have documented multiple myeloma as defined by the criteria below (a, b, and c):

   1. Monoclonal plasma cells in the bone marrow of ≥10% or presence of a biopsy proven plasmacytoma AND

   2. 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.

      OR

      • Anemia: hemoglobin value of >2.0 g/dL below the lower limit of normal, or a hemoglobin value <10.0 g/dL.

      OR

      • 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).

   3. 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
      • Light chain multiple myeloma without measurable disease in the urine: serum immunoglobulin (Ig) free light chains (FLC) ≥10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

7. Female subjects who:

   1. Are postmenopausal for at least one year before the screening visit, OR
   2. Are surgically sterile, OR

   3. Females of childbearing potential or male subjects with female partners of childbearing potential shall be required to use effective contraceptive methods (double barrier method, intrauterine device, oral contraception or abstinence) starting two weeks before first study drug(s) administration, while on therapy and for 16 weeks following the last dose of study drug(s). A woman is considered of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile. The following highly effective methods of contraception are accepted:

      • Established use of oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation.
      • Established use of oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation.
      • Placement of an intrauterine device or intrauterine hormone-releasing system.
      • Barrier methods of contraception: male condom with either cap, diaphragm or sponge with spermicide (double-barrier methods). The use of double-barrier methods should always be supplemented with the use of a spermicide. Female condom and male condom should not be used together.
      • Male sterilization (provided that the partner is the sole sexual partner of the patient and that the sterilized partner has received medical assessment of the surgical success).
      • Sexual abstinence.
      • Female subjects must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction starting two weeks before first study drug(s) administration, while on therapy and for 16 weeks following the last dose of study drug(s).

8. Male subjects, even if surgically sterilized (i.e., status postvasectomy), who:

   1. Agree to practice effective barrier contraception during the entire study treatment period from the time of signing the informed consent through and through four months after the last dose of study drug(s) (female and male condoms should not be used together), or
   2. Agree to practice true abstinence during the entire study treatment period from the time of signing the informed consent through 16 weeks after the last dose of study drug(s), when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)

Exclusion Criteria:

1. 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.

2. 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.
3. Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma.
4. 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.
5. 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.

6. 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.

7. 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.
   • Hemoglobin level ≤7.5 g/dL (≤5 mmol/L); blood transfusions to maintain hemoglobin >7.5 g/dL are acceptable.
   • Platelet count <75 × 109/L for subjects in whom <50% of bone marrow nucleated cells are plasma cells; otherwise platelet count <50 × 109/L; no platelet transfusions in the past seven days are allowed.
   • Alanine aminotransferase (ALT) level ≥2.5 × ULN
   • Aspartate aminotransferase (AST) level ≥2.5 × ULN
   • Total bilirubin level ≥1.5 × ULN, (except for Gilbert Syndrome: direct bilirubin ≥2 × ULN)
8. Known allergies, hypersensitivity (if not amenable to premedication with steroids, or H2 blockers), or intolerance to monoclonal antibodies or human proteins, isatuximab or its excipients or known sensitivity to mammalian-derived products.
9. Plasma cell leukemia (>2.0 × 10^9/L circulating plasma cells by standard differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and/or skin changes), or light-chain amyloidosis.
10. Known or suspected of not being able to comply with the study protocol (e.g., because of alcoholism, drug dependency, or psychological disorder) or the subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments.
11. Pregnant or breastfeeding or planning to become pregnant starting two weeks before first study drug(s) administration, while on therapy and for 16 weeks following the last dose of study drug(s).
12. Plans to father a child starting two weeks before first study drug(s) administration, while on therapy and for 16 weeks following the last dose of study drug(s).
13. Had major surgery within two weeks before Cycle 1, Day 1, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within two weeks after the last dose of study drug administration. Note: Subjects with planned surgical procedures to be conducted under local anesthesia are not excluded. Kyphoplasty is not considered a major surgery.
14. Patients with pre-existing uncontrolled pulmonary disease will be excluded; uncontrolled refers to patients having had at least one hospitalization due to pulmonary disease (for example, asthma, chronic obstructive pulmonary disease) within the six months prior to enrollment in the study; patients with previous history of pneumonitis will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Lead-in Cohort A; 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; Bortezomib (1.5 mg/m^2) subcutaneous on days 1, 8 and 15; Other Names: Velcade; Drug: Isatuximab; Isatuximab (10 mg/kg) IV on days 1, 8, 15 and 22; Other Names: SAR650984; Drug: Cyclophosphamide; Cyclophosphamide (250 mg/m^2) IV on days 1, 8 and 15; Other Names: Cytoxan; Neosar; cytophosphane; Drug: Dexamethasone; Dexamethasone 20 mg PO or IV (10 mg if >75 years) on days 1, 2, 8, 9, 15, 16, 22 and 23; Other Names: Decadron; Baycadron; TaperDex; ZoDex; DexPak; Zema-Pak; Zonacort
Experimental: Expansion Cohort A; 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; Bortezomib (1.5 mg/m^2) subcutaneous on days 1, 8 and 15; Other Names: Velcade; Drug: Isatuximab; Isatuximab (10 mg/kg) IV on days 1, 8, 15 and 22; Other Names: SAR650984; Drug: Cyclophosphamide; Cyclophosphamide (250 mg/m^2) IV on days 1, 8 and 15; Other Names: Cytoxan; Neosar; cytophosphane; Drug: Dexamethasone; Dexamethasone 20 mg PO or IV (10 mg if >75 years) on days 1, 2, 8, 9, 15, 16, 22 and 23; Other Names: Decadron; Baycadron; TaperDex; ZoDex; DexPak; Zema-Pak; Zonacort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of subjects who achieve partial response.	This will be measured using the International Myeloma Working Group criteria.	100 days following autologous stem cell transplant.
The number of subjects who achieve complete response.	This will be measured using the International Myeloma Working Group criteria.	100 days following autologous stem cell transplant.

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: Binod Dhakal, MD, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2021
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: January 22, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Renal Insufficiency; Isatuximab
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Renal Insufficiency; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Sulfonic Acids; Sulfur Acids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Benzenesulfonates; Arylsulfonates; Arylsulfonic Acids; Bortezomib; Dexamethasone; Cyclophosphamide; Calcium Dobesilate; isatuximab
• Other Study ID Numbers: PRO00036788

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes