Use of Isatuximab, Dexamethasone and Lenalidomide in a Go-Slow Fashion for Ultra-Frail Patients With Multiple Myeloma

Official title

Use of Isatuximab, Dexamethasone and Lenalidomide in a Go-Slow Fashion for Ultra-Frail Patients With Multiple Myeloma: A Phase 2 Multicenter Study

Overview

Historically, the frailest patients with multiple myeloma are under-represented in clinical trials, and have very high rates of treatment discontinuation, and early treatment mortality. The investigators hypothesize that a go-slow gentle approach to starting treatment in such patients, starting with just Isatuximab and dexamethasone with a gentle introduction to lenalidomide third cycle onwards, may improve treatment adherence and quality of life. The goal of this clinical trial is to learn if a go-slow approach to treating MM in ultra-frail patients may improve the ability to adhere to treatment and improve quality of life.

Interventions

• Drug Isatuximab
  Subcutaneous isatuximab will be administered weekly on a 28-day cycle during the first two cycles, and every two weeks of a 28-day cycle thereafter. Dexamethasone will be administered on the days of isatuximab administration and can be discontinued after two cycles of therapy, or continued at discretion of investigator. Lenalidomide, will be added after two cycles of therapy have been completed.

Primary outcome measures

• Completion rate of 9 cycles of treatment [Time frame: At the end of 9 cycles of treatment (each cycle is 28 days)]

Secondary outcome measures (7)

• Change in quality of life as per the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 domain [Time frame: At the end of 4 cycles of treatment (each cycle is 28 days)]
• Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type [Time frame: At study completion. Participants will be enrolled in study for about 3 years.]
• Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by severity (as defined by the NIH CTCAE, version 5.0) [Time frame: At study completion. Participants will be enrolled in study for about 3 years.]
• Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by seriousness [Time frame: At study completion. Participants will be enrolled in study for about 3 years.]
• Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by duration [Time frame: At study completion. Participants will be enrolled in study for about 3 years.]
• Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by relationship to study treatment [Time frame: At study completion. Participants will be enrolled in study for about 3 years.]
• Overall survival (OS) [Time frame: Time from registration until 3 years from start of therapy or death from any cause.]

Eligibility criteria

Inclusion criteria

• Male or female subject aged ≥ 18 years.
• Histologically confirmed myeloma and/or Plasma Cell Leukemia who are newly diagnosed and having completed ≤ 1 prior cycle of myeloma treatment.
• For female subjects of childbearing potential: Negative pregnancy test or evidence of post-menopausal status or evidence of permanent surgical sterilization (bilateral oophorectomy or hysterectomy). The post-menopausal status will be defined as having been amenorrheic for 24 months without an alternative medical cause.
• Subjects must be willing to follow contraception requirements listed in the protocol, agree to participate in the Lenalidomide REMS program, and have signed the Patient-Physician Agreement Form.
• Male subjects must agree to use a latex condom during intercourse for the duration of study therapy as described in the protocol, even if he has undergone a successful vasectomy.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy per the treating investigator.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
• IMWG defined frailty score ≥ 3. IMWG definition available here: http://www.myelomafrailtyscorecalculator.net

Exclusion criteria

• Receiving other investigational agents.
• Any condition that would, in the Investigator's judgment, compromise the subject's ability to understand the subject information, give informed consent, and/or contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[subjects may not receive the drug through a feeding tube\], social/ psychological issues, etc.)
• Known prior severe hypersensitivity (NCI CTCAE v5.0 Grade ≥ 3) to investigational product (IP) or any component in its formulations. This includes hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study intervention that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.
• Subjects currently taking prohibited medications as described in the protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Huntsman Cancer Institute at the University of Utah — Salt Lake City

Identifiers

NCT: NCT06517017 · HCI171326

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗