Clinical trial NCT04083898: Isatuximab, Bendamustine, and Prednisone in Refractory Multiple Myeloma
Official title: A Phase I/II Trial of Isatuximab, Bendamustine, and Prednisone in Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2019-09-10
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Isatuximab targets and kills CD38-positive myeloma cells in manner similar to rituximab's mechanism of action on CD20-positive lymphoma cells. Based on the synergy between rituximab and bendamustine, as well as the established clinical efficacy of bendamustine and isatuximab as single agents for multiple myeloma, the logical next step is to combine isatuximab with bendamustine and prednisone. Due to lack of effective therapies in refractory multiple myeloma, herein the investigators propose studying this novel combination in this population, in order to address a significant unmet need. The aim of the investigators is to first determine the maximal tolerated dose of the combination in participants with relapsed/refractory myeloma and then to establish the efficacy of this novel combination.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of multiple myeloma with a measurable disease parameter at time of screening. A measurable disease parameter is defined as one or more of the following:

  * Serum monoclonal protein ≥ 0.5 g/dL
  * 24 hour urine monoclonal protein ≥ 200 mg/24 hour
  * Serum free light chain ratio \> 5x normal ratio with an absolute difference of 10mg/dL between the involved and uninvolved free light chain
  * Soft tissue plasmacytoma ≥ 2 cm measurable by either physical examination and/or applicable radiographs (e.g. MRI, CT, etc.)
  * Bone marrow plasma cells ≥ 30%
* Triple-class-refractory disease defined as both of the following:

  * Previously received treatment with a proteasome inhibitor, an immunomodulatory drug, and daratumumab, in combination or as single-agents.
  * Refractory (defined per IMWG Consensus Criteria as disease that is nonresponsive while on therapy, or progresses within 60 days of last dose) to most recent therapy.
* At least 6 weeks from the last treatment with daratumumab to the first study treatment
* At least 18 years of age.
* Performance status of ECOG ≤ 2 Note: Participants with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible.
* Normal bone marrow and organ function as defined as ALL of the following:

  * Absolute neutrophil count ≥ 1500/mm3
  * Platelets ≥ 75,000/mm\^3 (transfusions not permitted within 7 days of screening)
  * ALT (SGPT) and AST (SGOT) \< 3.5 x the upper limit of the institutional normal value (ULN).
  * Total bilirubin ≤ 2.0 x mg/dL.
  * Creatinine clearance \> 30 ml/min using Cockcroft-Gault formula
* Females of childbearing potential (FCBP) must agree to refrain from becoming pregnant while on study drug and for 3 months after discontinuation from study drug, and must agree to use adequate contraception including hormonal contraception, (e.g. birth control pills, etc.), barrier method contraception (e.g. condoms), or abstinence during that time frame. Men engaging in sexual intercourse with a FCBP must agree to use adequate contraception including hormonal contraception, (e.g. birth control pills, etc), barrier method contraception (e.g. condoms), or abstinence while on study drug and for 3 months after discontinuation from study drug
* Ability to understand and willing to sign a written informed consent document.

Exclusion Criteria:

* Prior exposure to isatuximab or bendamustine
* History of plasma cell leukemia or MM CNS involvement.
* Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.
* Diagnosed with another concurrent malignancy requiring treatment.
* Active hepatitis A, B, or C.
* Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of study therapy.
* Receiving any other investigational agents within 14 days prior to enrollment.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
* Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
* Patients with HIV are eligible unless their CD4+ T-cell counts are \< 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.

Primary outcomes:
measure: Maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of regimen (Phase I only)
timeFrame: Completion of first cycle of treatment for all participants enrolled in Phase I portion (estimated to be 9 months)
measure: Overall response rate (ORR) (Phase II only)
timeFrame: 6 months
Secondary outcomes:
measure: Number of adverse events experienced by participants (Phase I and Phase II)
timeFrame: From start of treatment through 30 days after completion of treatment or initiation of new anti-myeloma therapy, whichever occurs first (estimated to be 7 months)
measure: Progression-free survival (PFS) (Phase II only)
timeFrame: Up to 5 years after removal from study (estimated to be 5 years and 6 months)
measure: Overall survival (OS) (Phase II only)
timeFrame: Up to 5 years after removal from study (estimated to be 5 years and 6 months)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Ravi Vij, M.D.
role: PRINCIPAL_INVESTIGATOR
References: