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cyclosporine in combination with carfilzomib and dexamethasone in patients with relapsed multiple myeloma refractory to carfilzomib with high expression of the PPIA gene in myeloma cells

patients will be treated with cyclosporine with dose titration based on repeated determinations of whole blood concentrations to achieve a target trough concentration of 250 ng/mL, in combination with carfilzomib plus dexamethasone.

cyclosporine in combination with carfilzomib and dexamethasone

Yeal Cohen, MD

Ella Krayzler

Yael Cohen, MD

This phase 1, open-label, single-arm, prospective, single center study will evaluate the safety, tolerability and efficacy of cyclosporine in combination with carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM).

This phase 1, open-label, single-arm, prospective, single center study will evaluate the safety, tolerability and efficacy of cyclosporine in combination with carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM). The patients will consist of adult men and women who have a confirmed diagnosis of RRMM, who have received at least two prior lines of therapy including carfilzomib, and were non responsive or refractory to carfilzomib as specified below, and who were found to have elevated expression of Peptidylprolyl Isomerase A (PPIA) in scRNA sequencing of their myeloma cells, and who meet other protocol outlined eligibility criteria.

The patients will be treated with cyclosporine with dose titration based on repeated determinations of whole blood concentrations to achieve a target trough concentration of 250 ng/mL, in combination with carfilzomib plus dexamethasone.

Patients may continue to receive treatment for 4 months or until disease progression or unacceptable toxicity, the earliest of them.

Subjects will be followed for Adverse Events (AEs), clinical status-Overall response rate (ORR) as defined by International Myeloma Working Group (IMWG) criteria, Progression Free Survival (PFS), Duration of Response (DOR), Time to Progression (TTP), stringent Complete Response (sCR 0, Complete Response (CR), Very Goog Partial Response (VGPR), Partial Response (PR), Depth of Best Response (DpR), Time To Response (TTR), Progressive Disease (PD), Overall Survival (OS) and laboratory parameters for up to 4 months, unless they terminate early due to disease progression, unacceptable toxicity or due to meeting one of the withdrawal criteria

Cyclosporine in Combination With Carfilzomib and Dexamethasone in Relapsed Multiple Myeloma Refractory to Carfilzomib and High Expression of PPIA Gene in Myeloma Cells

A Single-arm, Prospective Study of Cyclosporine in Combination With Carfilzomib and Dexamethasone in Patients With Relapsed Multiple Myeloma Refractory to Carfilzomib With High Expression of the Peptidylprolyl Isomerase A (PPIA) Gene in Myeloma Cells

Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment parameters.

Proportion of patients who achieve a best overall response of stringent complete response , complete response, very good partial response, or partial response as defined using the IMWG criteria

The time from first dose to the date of the first documented tumor progression or death due to any cause. PFS will be determined by an investigator, based upon laboratory data, as defined by the IMWG criteria

The time between the date of first response to the date of the first objectively documented tumor progression as assessed by study steering committee according to modified IMWG criteria or death due to any cause prior to subsequent anti-cancer therapy.

The time from the first dose to the date of the first sCR, CR, VGPR, or PR.

Time from initiation of treatment to documented PD

Time between the date of first dose and the date of death due to any cause

Kaplan Meyer test will be applied to test for differences between the groups in Progression Free Survival

Kaplan Meyer test will be applied to test for differences between the groups in Overall Survival

Spots Global Cancer Trial Database for cyclosporine in combination with carfilzomib and dexamethasone