Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Immunomodulating Agents

Lenalidomide

Dexamethasone acetate

Proteasome Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Carfilzomib (K):

* 20 mg/m2 IV on day 1 of cycle 1;
* 56 mg/m2 IV on days 8 and 15 in cycle 1;
* 56 mg/m2 IV on days 1, 8 and 15 in cycles 2-12;
* 56 mg/m2 on days 1 and 15 from cycle 13 and onwards.

Lenalidomide (R):

- 25 mg orally on days 1-21 of each cycle.

Dexamethasone (d):

- 40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycle.

Until PD or intolerance. Only patients that achieve at least a VGPR within the first year of treatment and in sustained MRD negativity (MRD negative at least at 10-5 after 1 and 2 years of therapy) will stop carfilzomib after 2 years of treatment, and will continue with lenalidomide and dexamethasone administration.

Lenalidomide (R):

-25 mg orally on days 1-21 of each cycle.

Dexamethasone (d):

-40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycles.

Until PD or intolerance.

* 20 mg/m2 IV on day 1 of cycle 1 enhanced to 56 mg/m2 on days 8, and 15 of cycle 1;
* 56 mg/m2 IV on days 1, 8 and 15 in cycles 2-12;
* 56 mg/m2 IV on days 1 and 15 from cycle 13 and onwards.

Carfilzomib

- 25 mg orally on days 1-21 of each cycle.

- 40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is to be repeated every 28 days. Patients that achieve at least a VGPR within the first year of study treatment and in sustained MRD negativity (MRD negative at least at 10-5 after 1 and 2 years of therapy) will stop carfilzomib administration after 2 years and will continue with lenalidomide and dexamethasone treatment until disease progression or intolerance to the therapy. Other patients will continue carfilzomib administration until disease progression or intolerance.

For patients \>75 years of age, the dose of dexamethasone is 20 mg/day on Days 1, 8, 15 and 22 of each treatment cycle.

Sara Bringhen

The combination of lenalidomide plus low-dose dexamethasone (Rd) is considered the new standard for elderly newly diagnosed multiple myeloma (NDMM) patients. The combination carfilzomib plus lenalidomide-dexamethasone (KRd) in relapsed-refractory MM patients improved the progression-free survival (PFS) of approximately 1 year compared to standard Rd treatment. In a small phase 2 trial (23 pts) the KRd combination in elderly NDMM pts showed a complete response (CR) rate of 79% and a PFS at 3 years of 80%. Cardiovascular adverse events are the most limiting toxicities, especially in elderly patients.

This protocol is a randomized, multicenter study designed to determine the MRD negativity and the PFS of KRd treatment regimen.

Patients will be randomized in a 1:1 ratio to receive carfilzomib-lenalidomide-dexamethasone (KRd - Arm A) or lenalidomide-dexamethasone (Rd - Arm B).

Patients will be stratified basing on international staging system (ISS) and fitness status using a web-based procedure completely concealed to study participants.

All consecutive patients ≥ 65 years with newly diagnosed MM will be enrolled in a large randomized study during a period of 24 months.

Patients will be treated until disease progression or intolerance to the therapy. The only exception is for patients enrolled in KRd arm who achieve at least a VGPR during the first year of treatment and in sustained MRD negativity (MRD negative at least at 10-5 after one and two years of therapy): these patients will stop carfilzomib administration after 2 years, whereas treatment with lenalidomide and dexamethasone will be continued.

A Trial That Compare Two Treatments in Newly Diagnosed Myeloma Patients Not Eligible for Transplant

Carfilzomib - Lenalidmide - Dexamethasone (KRd) Versus Lenalidomi - Dexamethasone (Rd) in Newly Diagnosed Myeloma Patients Not Eligible for Autologous Stem Cell Transplantation: a Randomized Phas III Trial

1. Minimal residual disease (MRD): unit of measure is not applicable, MRD is expressed as a pure number

2. Progression-free survival (PFS): unit of measure is not applicable, PFS is expressed as a pure number

Incidence of dose reduction and drug discontinuation in both treatment arms.

Benefit of proper cardiovascular baseline assessment and monitoring during treatment in both treatment arms:to mitigate major cardiovascular adverse event incidence, to prolong duration of treatment, to improve efficacy.

Safety as rate of dose reduction, drug discontinuation and toxicities

Response rate will include complete response (CR), very good partial response (VGPR) and partial response (PR) using the International Response Criteria. Responders are defined as subjects with at least a PR.

Time from randomization to objective tumor progression on next-line treatment or death from any cause.

Time to progression will be measured from the date of randomization to the date of first observation of PD, or deaths related to PD.

Time between first documentation of response and PD. Responders without disease progression will be censored either at the time of lost to FU, at the time of death due to other cause than PD, or at the end of the study.

Time between randomization and death. Subjects who die will be censored at time of death as an event, regardless cause of death.

Time to next therapy will be measured from the date of randomization to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event.

Correlation between MRD negativity and PFS, PFS2, TTP, TNT and OS

The following outcomes will be analysed in subgroups with different prognostic factors:

* Progression-free survival (PFS),
* Time to second disease progression (PFS2),
* Time to progression (TTP),
* Time to next therapy (TNT ),
* Overall survival (OS)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Trial That Compare Two Treatments in Newly Diagnosed Myeloma Patients Not Eligible for Transplant	NCT04096066	Multiple Myelom... New Diagnosis T...	Carfilzomib Lenalidomide Dexamethasone	65 Years -	Fondazione EMN Italy Onlus
A Trial That Compare Two Treatments in Newly Diagnosed Myeloma Patients Not Eligible for Transplant	NCT04096066	Multiple Myelom... New Diagnosis T...	Carfilzomib Lenalidomide Dexamethasone	65 Years -	Fondazione EMN Italy Onlus

Spots Global Cancer Trial Database for autologous stem cell transplantation ineligible