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

Lenalidomide

Dexamethasone acetate

Elotuzumab

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Participants will receive elotuzumab, carfilzomib, lenalidomide, and dexamethasone.

Participants will receive elotuzumab, lenalidomide, and dexamethasone.

Elotuzumab will be given on Cycles 1-2 on days 1, 8, 15, 22, Cycles 3 and Beyond on days 1 and 15

Carfilzomib will be given on Day 1 and 8 of Cycle 1, Days 1, 8, and 15 of Cycles 2-8, and Days 1 and 15 of Cycles 9 and beyond

Carfilzomib

Lenalidomide will be given on days 1-21 for all cycles.

Dexamethasone will be given as follows:

Cycle 1 and 2: Days 1, 2, 8, 9, 15, 16, and 22 Cycles 3 and Beyond: Days 1, 8, 15, and 22

Andrzej Jakubowiak, MD

This study will be a multi-center, open-label, Phase 2 study where newly diagnosed Multiple Myeloma requiring systemic chemotherapy will be eligible for enrollment. A total of 55 subjects will be enrolled. Time to progression or death will be calculated from the date of first treatment on protocol until the date of disease progression or death from any cause. Patients can expect to participate between 12-24 cycles. The primary endpoint will be the rate of response by next generation gene sequencing at the end of 8 cycles among non-transplant candidates and transplant candidates who agreed to defer transplant.

Primary Objective

• The primary efficacy endpoint will be the rate of sCR and/or the rate of negative MRD by next generation gene sequencing (NGS) by clonoSIGHT (Adaptive Biotechnologies) at the end of 8 cycles among non-transplant candidates and transplant candidates who agreed to defer transplant

Secondary Objectives

* To evaluate the safety and tolerability of elotuzumab in combination with KRd, when administered to subjects with newly diagnosed multiple myeloma.
* To determine the rate of MRD by next generation gene sequencing (NGS) by clonoSIGHT (Adaptive Biotechnologies) and by multi-color flow cytometry (MFC) at the end of Cycle 4, 8,and 12 for all subjects, and end of C18 (for subjects who are MRD+ at the end of C8 but MRD- at the end of C12 only), 24 months after C1D1, and yearly after that.
* To estimate time to event, including duration of response (DOR), progression-free survival (PFS), time to progression (TTP), and overall survival (OS).

Exploratory Objectives

* GEP, proteomics, and gene sequencing to evaluate the correlation between treatment outcome and pre-treatment subject profile.
* Immunologic correlative studies including FcγRIIIa V genotype.

All participants will receive E-KRd regimen (elotuzumab, carfilzomib, lenalidomide, and dexamethasone) for up to 12 Cycles.

After Cycle 12, participants that are MRD negative will move to E-Rd (elotuzumab, carfilzomib, lenalidomide, and dexamethasone) maintenance regimen and continue until disease progression. Participants that are MRD positive will continue to receive E-KRd regimen for an additional 6 cycles followed by E-Rd maintenance regimen and continue until disease progression

Study of Initial Treatment With Elotuzumab, Carfilzomib, Lenalidomide and Dexamethasone in Multiple Myeloma

Open-label, Single-arm, Phase 2 Study of Initial Treatment With Elotuzumab, Carfilzomib (Kyprolis), Lenalidomide (Revlimid) and Low Dose Dexamethasone (E-KRd) in Newly Diagnosed, Multiple Myeloma Requiring Systemic Chemotherapy

Subjects will have the option to participate in additional genetic components of this trial if they provide their consent. Once a subject has completed participation in the trial, if they agree to participate in the optional components their disease will be analyzed in relation to people with similar genetic make up.

Adverse events will be monitored in real time and discussed at a weekly data and safety monitoring conference.

These events will be analyzed at differing points of time based on the individual subjects disease progression.

Bristol-Myers Squibb

Amgen

Multiple Myeloma Research Foundation

University of Chicago

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphatic Diseases

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lenalidomide daily for 3 weeks every 4 weeks for 24 months

Placebo daily for 3 weeks every 4 weeks for 24 months

Daily for 3 weeks every 4 weeks for 24 months

Placebo

This study is designed as a phase III, randomized, double-blind, placebo-controlled trial to explore the effect of maintenance therapy with lenalidomide versus placebo on progression-free survival (PFS) in patients treated with R-CHOP responding to induction therapy

For the primary efficacy variable, PFS, an improvement in median PFS from 38.6 months for Treatment Arm B to 54 months for Treatment Arm A (corresponding to a 2-year PFS of 65% vs 73.6%), is considered clinically relevant.

Patients should have received at least 6 and up to 8 cycles of the R-CHOP 14 or R-CHOP 21 regimen or 6 R-CHOP-14 or -21 completed by 2 Rituximab alone in accordance to local preferences.

Patients can be registered to participate in the study at two time points:

* At time of initial diagnosis and study enrolment (signature of informed consent) before the first cycle of treatment with R-CHOP.
* At randomization (signature of informed consent) after treatment in first line with R-CHOP and have reached at least PR or CR.

Evaluation of the response to R-CHOP must be in accordance with Revised Response Criteria for Malignant Lymphoma(2007).

Stratification: Before randomization, the patients will be stratified according to the country and the response to R-CHOP (PR vs CR).

Randomization: Patients in CR/PR after R-CHOP will be randomized to maintenance therapy with lenalidomide or placebo.

Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP

Double Blind Randomized Phase III Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP in First Line

PFS will be measured from the date of randomization to the date of first documented disease progression or death. Progression data will be assigned to the earliest time when any progression is observed without prior missing assessments during the study up to the end of the follow up phase.

From the date of randomization to the date of death from any cause Interim analysis of OS will be performed at the time of the PFS final analysis; it is projected to have 97 deaths at this time. Final analysis of OS at the end of the study, defined by the last visit of follow-up for the last patient randomized, 5 years after its randomization

From the date of randomization to the date of first documented disease progression, relapse, initiation of new anti-lymphoma therapy or death from any cause Interim analysis of EFS will be performed at the time of the PFS final analysis. Final analysis of OS at the end of the study, defined by the last visit of follow-up for the last patient randomized, 5 years after its randomization

Toxicities occured during maintenance phase will be measured and reported from grade 2 for infection and neurological toxicities and from grade 3 for other toxicities according to CTCAE v3

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

The Lymphoma Academic Research Organisation

Melphalan

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Treatment phase (28 days/cycle x 6 cycles):

Lenalidomide: 10 mg/day orally on days 1-21, followed by 7 days of rest. Melphalan: 4 mg/m2 daily on days 1-4. Dexamethasone: 40 mg daily on days 1, 8, 15 and 22.

Maintenance Phase (for subjects who achieve partial response or better at the end of the treatment phase):

lenalidomide: 10 mg/day orally on days 1-21 followed by 7 days of rest (28 days/cycle) for a maximum of 24 cycles.

Lenalidomide (Revlimid)

Hearn J Cho, MD

This study is to determine whether addition of Revlimid to standard therapy will increase overall and complete response rates compared to historical standard frontline therapy and whether this combination treatment has fewer side effects than similar combination induction treatment.

Current multiple myeloma therapies, typically an induction regimen followed by consolidation therapy with high dose chemotherapy and autologous stem cell rescue (autologous transplantation), can induce remission but relapse and death are inevitable. A growing body of literature suggests that consolidation therapy with autologous transplantation does not confer additional survival benefit and may have increased procedure-related morbidity and mortality in patients over 65 years old. Autologous transplantation is no longer recommended as standard care for this population. In addition, certain patients may not be eligible for autologous transplantation due to co-morbid medical conditions or may elect not to undergo the procedure for personal reasons.

The historic standard of care for multiple myeloma patients who were not eligible for autologous transplantation for consolidation was induction therapy with melphalan/ prednisone (MP), often followed by some form of maintenance therapy after achievement of complete or partial remission. A recent phase 3 study showed that the addition of thalidomide to MP (MPT) demonstrated higher overall and complete response rates. For patients who are eligible for autologous transplantation, thalidomide/ dexamethasone (Thal Dex) induction therapy is considered the standard of care, but a phase 2 study of lenalidomide (Revlimid)/ dexamethasone (Rev Dex) induction therapy demonstrated higher overall and complete response rates compared to Thal Dex. In addition, lenalidomide has a favorable side effect profile compared to thalidomide. Based on these data, we hypothesize that the combination of Revlimid/ melphalan/ dexamethasone (ReMeDex) induction therapy for myeloma patients who are not planned for autologous transplantation due to age restriction or other factors may demonstrate higher overall and/ or complete response rates with fewer side effects.

Combination of Revlimid, Melphalan and Dexamethasone as First Line Treatment for Multiple Myeloma

Phase II Study of Revlimid (Lenalidomide), Melphalan, and Dexamethasone (ReMeDex) for Newly Diagnosed Multiple Myeloma Patients Not Undergoing Autologous Transplantation

Toxicity will be scored using CTCAE version 3.0 for toxicity and adverse event reporting.

Progressive Disease: requires any one or more of the following:

1. Increase of ≥25% from baseline in Serum M-component and/or (the absolute increase must be ≥0.5 g/dl)b
2. Urine M-component and/or (the absolute increase must be ≥200 mg/24 h
3. Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 mg/dl.
4. Bone marrow plasma cell percentage: the absolute % must be ≥10%c
5. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
6. Development of hypercalcemia (corrected serum calcium \>11.5 mg/dl or 2.65 mmol/l) that can be attributed solely to the plasma cell proliferative disorder

Celgene

NYU Langone Health

Only 7 out of 8 patients were treated. The percentage of affected patients was based on those 7.

ReMeDex

Age, Categorical

Age, Continuous

Sex: Female, Male

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

More than one race

Unknown or Not Reported

Race/Ethnicity, Customized

United States

Region of Enrollment

Hearn J. Cho, MD

No data are available because data were not collected. Pi left the institution and slow accrual did not allow for sufficient data collection prior to PI leaving institution. No data were analyzed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Initial Treatment With Elotuzumab, Carfilzomib, Lenalidomide and Dexamethasone in Multiple Myeloma	NCT02969837	Multiple Myelom...	Elotuzumab Carfilzomib Lenalidomide Dexamethasone	18 Years -	University of Chicago
Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP	NCT01122472	Lymphoma Diffuse Large B...	Lenalidomide Placebo	60 Years - 80 Years	The Lymphoma Academic Research Organisation
Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP	NCT01122472	Lymphoma Diffuse Large B...	Lenalidomide Placebo	60 Years - 80 Years	The Lymphoma Academic Research Organisation
Combination of Revlimid, Melphalan and Dexamethasone as First Line Treatment for Multiple Myeloma	NCT00843310	Multiple Myelom...	Lenalidomide (R... Melphalan Dexamethasone	18 Years -	NYU Langone Health

Spots Global Cancer Trial Database for lenalidomide (revlimid)