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

Recruiting now · Phase 2

Conditions studied: Multiple Myeloma

In brief

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

Key facts

Study ID

NCT04240054

Run by

Medical College of Wisconsin

People needed

41

Starts

2021-11-02

Expected to finish

2030-12-01

Last updated by the study team

2026-01-28

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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.
• 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).
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Female subjects who:
• Are postmenopausal for at least one year before the screening visit, OR
• Are surgically sterile, OR
• 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.

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.
• 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)
• 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.
• 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.
• 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.
• 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).
• 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).

Where it is running

• Froedtert Hospital & the Medical College of Wisconsin — Milwaukee, Wisconsin, United States (enrolling)

Full record on ClinicalTrials.gov

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