Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Disease Progression

Recurrence

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Disease Attributes

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Anti-Infective Agents

Dexamethasone

Lenalidomide

Dexamethasone acetate

BB 1101

Thalidomide

Elotuzumab

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Immunosuppressive Agents

Anti-Bacterial Agents

Elotuzumab 10 mg/kg intravenously (IV) weekly (days 1, 8, 15 and 22) for 2 cycles, then 20 mg/kg every 4 weeks. Dexamethasone will be administered as premedication for elotuzumab.

Lenalidomide 25 mg by mouth (PO) daily days 1-21 out of a 28-day schedule.

Elotuzumab 10 mg/kg IV weekly (days 1, 8, 15 and 22) for 2 cycles, then 20 mg/kg every 4 weeks. Dexamethasone will be administered as premedication for elotuzumab.

Lenalidomide 10 mg PO daily days 1-21 out of a 28-day schedule.

Elotuzumab according to dosing schedule outlined in treatment arms.

Lenalidomide according to dosing schedule outlined in treatment arms.

Dexamethasone is a commercially available drug. The description, how supplied, and storage instructions for dexamethasone product are found in the prescribing information.

During the study, dexamethasone will be administered as premedication for elotuzumab as indicated in the package insert.

Melissa Alsina, M.D.

The purpose of this study is determine Time-to-Progression with elotuzumab plus lenalidomide when elotuzumab is added to multiple myeloma participants with serologic relapse/progression while receiving lenalidomide maintenance for each study arm.

This is a randomized parallel 2-cohort phase 2 study of elotuzumab given at 10 mg/kg weekly during induction in combination with lenalidomide (either 25 mg or 10 mg) in patients with multiple myeloma who progress or relapse serologically while on single agent lenalidomide maintenance.

The combination therapy with elotuzumab and lenalidomide will be continued until further progression of myeloma (based on response criteria) or intolerability.

Elotuzumab Plus Lenalidomide (Elo/Rev) for Serologic Relapse/Progression While on Lenalidomide

A Randomized Parallel Phase 2 Study of Elotuzumab Plus Lenalidomide (Elo/Rev) for the Treatment of Serologic Relapse/Progression While on Lenalidomide Maintenance for Multiple Myeloma

Progression free survival (PFS) is defined as the time of randomization to date of death from any cause, date of relapse/progression, or the last follow-up date, whichever comes first. The Kaplan-Meier method will be used to estimate PFS for each Study Arm. The method of Brookmeyer and Crowley will be used to construct 95% confidence interval.

Overall response with elotuzumab and lenalidomide for each study arm. Overall Response is defined as best Overall Response, as Complete Response or Partial Response. Response will be assessed per the uniform response criteria of the International Myeloma Working Group(IMWG). Myeloma participants enrolled in this clinical study will be assessed for disease response after every cycle. Complete Response= Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates; Partial Response= ≥50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by ≥90% or to \<200 mg per 24 h;

Minimum response (MR) or better with elotuzumab and lenalidomide for each study arm. The Consensus on Uniform Reporting of Response will be used to evaluate response. Myeloma participants enrolled in this clinical study will be assessed for disease response after every cycle.

Bristol-Myers Squibb

H. Lee Moffitt Cancer Center and Research Institute

Elotuzumab 10 mg/kg intravenously (IV) weekly (days 1, 8, 15 and 22) for 2 cycles, then 20 mg/kg every 4 weeks. Dexamethasone will be administered as premedication for elotuzumab.

Lenalidomide 25 mg by mouth (PO) daily days 1-21 out of a 28-day schedule.

Elotuzumab: Elotuzumab according to dosing schedule outlined in treatment arms.

Lenalidomide: Lenalidomide according to dosing schedule outlined in treatment arms.

Dexamethasone: Dexamethasone is a commercially available drug. The description, how supplied, and storage instructions for dexamethasone product are found in the prescribing information.

During the study, dexamethasone will be administered as premedication for elotuzumab as indicated in the package insert.

A: Elotuzumab + Lenalidomide at 25 mg

Elotuzumab 10 mg/kg IV weekly (days 1, 8, 15 and 22) for 2 cycles, then 20 mg/kg every 4 weeks. Dexamethasone will be administered as premedication for elotuzumab.

Lenalidomide 10 mg PO daily days 1-21 out of a 28-day schedule.

Elotuzumab: Elotuzumab according to dosing schedule outlined in treatment arms.

Lenalidomide: Lenalidomide according to dosing schedule outlined in treatment arms.

Dexamethasone: Dexamethasone is a commercially available drug. The description, how supplied, and storage instructions for dexamethasone product are found in the prescribing information.

During the study, dexamethasone will be administered as premedication for elotuzumab as indicated in the package insert.

B: Elotuzumab + Lenalidomide at 10 mg

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Melissa Alsina

Percentage of Participants With Progression Free Survival (PFS)

Overall Response

Minimum Response (MR)

Overall Study

Melphalan

Antineoplastic Agents, Alkylating

Alkylating Agents

Melphalan will be given on Day -2 and Day -1. Lenalidomide will be given from Day -7 to Day +2.

Patients will receive a fixed dose of melphalan, while the dose of lenalidomide is escalated according to the protocol defined cohorts. Lenalidomide is given on day -7 to day +2, while intravenous melphalan is given on day -2 and -1. Lenalidomide dosing will be in the morning at approximately the same time each day.

Lenalidomide plus Melphalan during autologous stem cell transplantation

Lenalidomide maintenance therapy will begin on Day +100 to Day +110 provided the protocol-defined criteria are met. The initial starting dose of lenalidomide during maintenance is 10 mg daily on Days 1-28 of each 28-day cycle.

Lenalidomide maintenance

Attaya Suvannasankha, MD

This is a research study for newly diagnosed multiple myeloma or multiple myeloma has returned (relapsed). Multiple myeloma is a type of cancer that begins in white blood cells called plasma cells. Plasma cells make proteins that help fight infections. Current therapy for multiple myeloma includes high dose chemotherapy and autologous (patient's own cells) stem cell transplantation.

There will be two parts (or phases) to this study:

The purpose of the first part is to find the highest dose of a drug called lenalidomide (Revlimid®) that can be given in combination with high dose melphalan without causing severe adverse events.

The purpose of the second part is to find out the effects of this treatment (good and bad) on multiple myeloma patients.

Lenalidomide is a drug that interferes with the development of tiny blood vessels that help tumors grow. Lenalidomide in combination with dexamethasone is approved by the Food and Drug Administration (FDA) for the treatment of relapsed multiple myeloma. It is also approved for the treatment of specific types of myelodysplastic syndrome (MDS), another blood cancer. Other research studies using lenalidomide in combination with other drugs in subjects with newly diagnosed multiple myeloma also show good response rate.

High dose melphalan is approved by the FDA and is commonly used in multiple myeloma treatment prior to stem cell transplantation. This combination of lenalidomide, high-dose melphalan and stem cell transplantation has not been studied in newly diagnosed and relapsed multiple myeloma, so it is considered experimental. In research studies, "experimental" refers to a drug or procedure that has undergone basic laboratory testing and received approval from the US Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered experimental in other diseases or conditions.

In this study, lenalidomide will be given together with melphalan (chemotherapy) with the hope that more disease will be killed before the stem cell transplant. Three months after the transplant, patients will take lenalidomide again with the hope that this will help prolong the time when the disease is in remission.

All patients will receive melphalan 100 milligrams (mg) per meters squared (m2) intravenously day -2 and day -1. Phase I patients will be enrolled sequentially into one of dose levels below and administered the corresponding lenalidomide dose. The recommended phase II dose based on dose limiting toxicities observed in the phase I portion will be used for lenalidomide dosing in the phase II portion of the trial Dose level -1 Lenalidomide 25 mg daily day -7 to day +2, Dose level 1 Lenalidomide 50 mg daily day -7 to day +2, Dose level 2 Lenalidomide 75 mg daily day -7 to day +2, Dose level 3 Lenalidomide 100 mg daily day -7 to day +2, Dose level 4 Lenalidomide 150 mg daily day -7 to day +2,

Lenalidomide and High Dose Melphalan Followed by Autologous Stem Cell Transplant in Multiple Myeloma

Phase I/II Study of Oral Lenalidomide and High Dose Melphalan Supported by Autologous Peripheral Blood Stem Cell Infusion for Patients With Multiple Myeloma

The number of patients who had a DLT during the dose finding portion (Phase I) of the trial for the safety of lenalidomide when used in combination with high dose melphalan in the setting of autologous stem cell transplantation in patients with multiple myeloma.

Evaluate the overall response rate of patients receiving therapy. Patients are considered as having a response if their overall response is Partial Response or better (CR+sCR+VGPR+PR). The percentage of patients achieving this and the exact 95% confidence interval will be calculated. Responses will be defined using the response criteria determined by the International Working Group for Multiple Myeloma (CR= Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and 5% plasma cells in bone marrow; sCR=CR as defined above plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunoflurorescence; VGPR=Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-component plus urine M-component\<100 mg per 24 h; PR=\>=50% reduction of serum M-protein and reduction in 24-h urinary M-protein by \>=90% or to \<200mg per 24 h).

Number of unique patients who had a treatment-related (possible, probable or definite) adverse events that were graded 3 or higher.

Celgene

Attaya Suvannasankha

Assistant Professor of Clinical Medicine

All patients will receive Melphalan 100 mg/m2 intravenously day -2 and day -1 and Lenalidomide 50 mg given daily day -7 to day +2

Phase I, Dose Level 1

All patients will receive Melphalan 100 mg/m2 intravenously day -2 and day -1 and Lenalidomide 75 mg given daily day -7 to day +2

Phase I, Dose Level 2

All patients will receive Melphalan 100 mg/m2 intravenously day -2 and day -1 and Lenalidomide 100 mg given daily day -7 to day +2

Phase I, Dose Level 3

All patients will receive Melphalan 100 mg/m2 intravenously day -2 and day -1 and Lenalidomide 150 mg given daily day -7 to day +2

Phase I, Dose Level 4

Phase II

Age, Continuous

Dr. Attaya Suvannasankha

All Phase I patients receiving at least one dose of study drug and having at least one evaluable post-baseline visit (16 patients)

Phase I: Number of Patients With Dose Limiting Toxicity

All Phase II patients who received at least one dose of study drug and had at least one evaluable post-baseline visit

Phase II: Overall Response Rate

All Phase II patients who received treatment.

Phase II: Treatment-Related Adverse Events Grade 3 or Higher

Prednisone

Bortezomib

after 6 cycles VMP Patients will receive Lenalidomide given as two capsules 5 mg capsules p.o. daily until progressive disease (PD)

after 6 cycles VMP Patients will receive Placebo given as two capsules 5 mg capsules p.o. daily until progressive disease (PD)

Placebo

Annamaria Brioli, MD

This is a multicenter, randomized, blinded, 2-arm phase IIb trial that will compare the efficacy and safety of Lenalidomide maintenance after Bortezomib/Melphalan/Prednison (VMP) induction to VMP without maintenance (Placebo). In addition the trial will assess the treatment of Revlimid/low dose Dexamethasone (Rd) as Salvage after VMP without sufficient response (less than PR) in an observational arm. Key eligibility criteria include patients with newly diagnosed multiple myeloma and who are 65 years of age or older or are not candidates for high-dose chemotherapy and autologous stem cell transplantation. Patients with poor performance status or serious coexistent medical conditions will be excluded from this study. After registration all patients receive 6 cycles VMP (modified according to Mateos et al.). Patients who receive at least a PR and completed VMP can be randomized to either Lenalidomide 10 mg/d continuously maintenance or to placebo. Randomization will be stratified according to the quality of response after VMP induction (PR vs. VGPR + stringent complete remission \[sCR\] + CR). Patients that are not able to complete VMP due to toxicity but reached at least a PR after a minimum of four cycles of therapy should immediately proceed to randomization. Blinded phase continues until progression or end of study. After unblinding, patients who received placebo should be treated with Rd.

Patients that do not reach PR after induction with VMP or are progressive during treatment with VMP should not be randomized, but switched to the observation arm and treated with Rd immediately. The study treatment ends with the confirmed progression on maintenance treatment (Lenalidomide or placebo) for patients that reached PR with induction treatment, or with the confirmed progression on second-line therapy with Revlimid® and Dexamethasone for patients that did not reach PR on induction treatment. All patients will be followed up every 3 months after end of study treatment, until end of study. The study ends two years after Last Patient In (i.e. randomization for maintenance) if sufficient events for the primary endpoint were received, but not later than 8 years after trial initiation (whatever comes first).

Primary objective

- Estimate the gain in progression-free survival (PFS) by maintenance with Lenalidomide after induction with VMP in elderly patients or patients unfit for highdose chemotherapy in comparison with placebo after VMP

Secondary study objectives

* To compare response rates of VMP and Lenalidomide maintenance versus VMP and placebo
* To compare overall survival probabilities between patients treated with Lenalidomide maintenance and patients without maintenance treatment
* To compare the safety of VMP and Lenalidomide maintenance versus VMP and placebo
* To compare the QoL of VMP and Lenalidomide maintenance versus VMP and placebo
* To assess the safety and efficacy of Rd for poor responders on VMP

Treatment Optimization in Patients With Untreated Multiple Myeloma

Phase II Study of Bortezomib, Melphalan, Prednisone (VMP) Followed by Lenalidomide Maintenance vs. VMP Without Maintenance in Myeloma Patients Not Eligible to High-dose Chemotherapy and Autologous Stem Cell Transplantation

time from randomization to the first documentation of disease progression or death due to any cause, whichever comes first, assessed up to the end of the study (maximum of 8 years)

defined as time from initial registration before start of VMP treatment to the first documentation of disease progression based on the International Myeloma Working Group (IMWG) criteria, or death due to any cause during the study up to the end of the PFS follow-up phase

complete response \[CR\], stringent complete response \[sCR\], very good partial response (VGPR), partial response \[PR\], and overall response \[CR + VGPR + PR\] using IMWG criteria

time of first study treatment until up to the end of the follow-up phase (maximum of 8 years)

initial registration up to the end of the follow-up phase (maximum of 8 years), European Organization for Research and Treatment of Cancer (EORTC) QLQ (Quality of Life)-C30, QLQ-MY20 (Myeloma 20), EQ (European Questionnaire)-5D

defined as a composite endpoint measuring time from randomization to discontinuation of study treatment for any reason, including disease progression, treatment toxicity, start of another anti-myeloma treatment, and death, whichever comes first

time from registration before start of VMP treatment until death due to any cause or until censoring at the last time the patient was known to be alive

Dr. med. Lars-Olof Muegge

\[KRd #1\~6, Every 4 weeks\] D1, 2, 8, 9, 15,16 Carfilzomib 20mg/m2 + 5% dextrose in water 50 mL over 10 mins (From Cycle1Day8 27mg/m2) D1 - 21 Lenalidomide 25mg P.O. D1, 8, 15, 22 Dexamethasone 40mg IV or PO

\[Autologous stem cell transplantation phase\]

\[Lenalidomide maintenance phase, Every 4 weeks\] D1-28 Lenalidomide 10 mg

Lenalidomide maintenance after carfilzomib, lenalidomide, and dexamethasone re-induction followed by the 2nd ASCT.

Kihyun Kim, M.D., Ph.D

Hyunju Park

Kihyun Kim

The purpose of this study is to evaluate the efficacy and safety of salvage treatment with carfilzomib/lenalidomide/dexamethasone (KRD) followed by 2nd autologous stem cell transplantation (ASCT) and lenalidomide maintenance in patients with relapsed myeloma after 1st ASCT.

This is a single-arm phase II study to assess the efficacy and safety of KRD followed by 2nd ASCT - lenalidomide maintenance for 18 months in patients with relapsed multiple myeloma after 1st ASCT who are 70 years of age or younger. A total of 58 participants will be recruited. As a re-induction therapy 6 cycles of KRD (K, 27mg/m2, D1,2,8,9,15,16; R, 25 mg, D1-21; D, 40mg weekly, every 28 days) will be administered. If a patient achieves at least partial response, 2nd ASCT + lenalidomide 10mg for 18 months will be proceeded. Study will be continued until disease progression, unacceptable toxicity, or completion of pre-planned schedule. Response will be assessed using the International Myeloma Working Group(IMWG) response criteria and the safety profiles will be described using the NCI-CTCAE v5.0. Participants who discontinue therapy will be followed every 3 months for 3 years if they are on subsequent treatment, disease-free or dead.

Carfilzomib, Lenalidomide, and Dexamethasone Re-induction Followed by the 2nd ASCT in Multiple Myeloma Patients Relapsed After the 1st ASCT

Phase II, Single-arm Trial of Carfilzomib, Lenalidomide, and Dexamethasone Re-induction Followed by the 2nd ASCT in Multiple Myeloma Patients Relapsed After the 1st ASCT

percentage of patients who are disease free or alive at 2-years

percentage of patients who achieve complete response

percentage of patients who achieve at least partial response

from the time of written consent to the time of achieving at least partial response

from the time of achieving at least partial response to the time of progressive disease

from the time of written consent to the time of death or last follow-up

percentage of patients who collected cluster of differentiation(CD34+) hematopoietic stem cells \> 2 x 10\^6 cells/kg

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Elotuzumab Plus Lenalidomide (Elo/Rev) for Serologic Relapse/Progression While on Lenalidomide	NCT03411031	Multiple Myelom...	Elotuzumab Lenalidomide Dexamethasone	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Lenalidomide and High Dose Melphalan Followed by Autologous Stem Cell Transplant in Multiple Myeloma	NCT01142232	Multiple Myelom...	Lenalidomide pl... Lenalidomide ma...	18 Years -	Indiana University
Treatment Optimization in Patients With Untreated Multiple Myeloma	NCT02145598	Multiple Myelom...	Lenalidomide Placebo	18 Years -	University of Jena
Carfilzomib, Lenalidomide, and Dexamethasone Re-induction Followed by the 2nd ASCT in Multiple Myeloma Patients Relapsed After the 1st ASCT	NCT05497102	Multiple Myelom...	Lenalidomide ma...	20 Years - 70 Years	Samsung Medical Center

Spots Global Cancer Trial Database for lenalidomide maintenance