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

Antipyretics

Analgesics

Anti-Allergic Agents

Central Nervous System Depressants

Dermatologic Agents

Respiratory System Agents

Dexamethasone

Acetaminophen

Lenalidomide

Bortezomib

Daratumumab

Dexamethasone acetate

Diphenhydramine

Promethazine

Montelukast

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Analgesics, Non-Narcotic

Anti-Asthmatic Agents

Leukotriene Antagonists

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Histamine H1 Antagonists

Histamine

Histamine phosphate

Histamine Antagonists

Neurotransmitter Agents

Participants in this group will receive Bortezomib, Lenalidomide and Dexamethasone on a 21 day treatment cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.

Participants in this group will receive Carfilzomib, Lenalidomide and Dexamethasone on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.

Participants in this group will receive Carfilzomib, Lenalidomide, Dexamethasone with Daratumumab, Acetaminophen, Diphenhydramine and Montelukast on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.

1.3 mg/m2 administered Subcutaneous (SC) or intravenous (IV) on days 1, 4, 8 and 11 of a 21 day treatment cycle for participants randomized to Arm A.

20 mg or 40 mg per dose administered by mouth (PO) or IV.

Participants randomized in Arm A:

20 mg/dose on days 1, 4, 8 and 11 on a 21 day treatment cycle;

Participants randomized in Arm B:

Cycles 1 through 8 - 40mg/dose on days 1, 8 and 15 on a 28-day cycle

Participants randomized in Arm C:

Cycle 1-2 - 40 mg/dose on days 1, 8, 15 and 22 on a 28-day cycle; Cycles 3-8 - 40mg/dose on Days 1, 8, 15 on a 28-day cycle;

10 or 25 mg/day capsules administered PO.

Participants randomized in Arm A:

25 mg/day capsules on Days 1 through 14 of a 21 day cycle.;

Participants randomized in Arm B:

Cycles 1 through 8 - 25 mg/day capsules on Days 1 through 21 of a 28 day cycle;

Participants randomized in Arm C:

Cycles 1 - 25 mg/day capsules on Days 2 through 21 of a 28 day cycle; Cycles 2 through 8 - 25 mg/day capsules on Days 1 through 21 of a 28 day cycle;

Maintenance Therapy:

10 mg capsules on Days 1 through 21 on a 28 days cycle.

650 mg administered PO.

Participants randomized to Arm C:

Cycles 1 through 8 - 650 mg administered on Days 1, 8 and 15.

25 mg administered via IV

Participants randomized to Arm C:

Cycles 1 through 8 - 25 mg administered on Days 1, 8 and 15.

10 mg administered PO to participants randomized to Arm C prior to the first 4 doses of Daratumumab.

20 mg or 56 mg/m2 per dose administered via IV.

Participants randomized to Arm B:

Cycle 1 - 20 mg/m2 per dose on Day 1 and 56 mg/m2 per dose on days 8 and 15 of a 28 day cycle; Cycles 2 through 8 - 56 mg/m2 per dose on days 1, 8 and 15 of a 28 day cycle;

Participants randomized to Arm C:

Cycle 1 - 20 mg/m2 per dose on Day 2 and 56 mg/m2 per dose on days 8 and 15 of a 28 day cycle; Cycles 2 through 8 - 56 mg/m2 per dose on days 1, 8 and 15 of a 28 day cycle

Carfilzomib

16 mg/kg administered via IV or 1800 mg SC, per treating physician discretion.

Participants randomized to Arm C:

Cycles 1 though 2 - 16 mg/kg IV or 1800 mg SC on days 1, 8, 15, and 22 of a 28 day cycle; Cycles 3 through 6- 16 mg/kg IV or 1800 mg SC on days 1 and 15 of a 28 day cycle; Cycles 7 through 8 - 16 mg/kg IV or 1800 mg SC on day 1 of a 28 day cycle

Participants who are MRD positive at the conclusion of 8 cycles of study treatment, and were able to have their stem cells that were extracted, will receive ASCT from participants' bone marrow samples.

Autologous Stem Cell Transplant (ASCT)

Philip Arlen

Philip Arlen, MD

Carl Landgren, MD

Ken Shain, MD

Ariffa Kariapper

Jens Hillengass, MD

Aisha Hashmi

Thomas Jandl, MD

Elisabet Manasanch, MD

Douglas Sborov, MD

This study is being done to find out whether carfilzomib, lenalidomide, and dexamethasone (KRD) or KRD and Daratumumab (KRD+DARA) might be safer and more effective ways of controlling multiple myeloma than the stand or care treatment, which is lenalidomide, bortezomib, and dexamethasone (VRD).

Per protocol amendment version 4.0 (May 23, 2022), Arm A will be closed and no additional participants will be enrolled in this arm.

A Study of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly-Diagnosed Multiple Myeloma

Phase 2, Open-Label Randomized Study of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone vs Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

MRD will be assessed by the MRD scale ranging from 10 (increased disease detection) to -5 (less to no disease detection) after 8 cycles of therapy.

Overall survival is defined as the time from date of randomization to death from any cause

PFS is defined as time from date of randomization to time of progression or death, whichever occurs first.

EFS is defined as time from date of randomization to the time of 1) achieving a PR or less with the first four cycles of therapy, 2) transplant, 3) progression, or 4) death, whichever occurs first.

Rate of Response will be reported as the percentage of participants achieving a response of: a) Partial Response (PR) or better, b) Very Good Partial Response (VGPR) or better and c) Complete Response (CR) and Stringent Complete Response (sCR). Responses will be evaluated from participant serum, urine and bone marrow samples.

MRD will be evaluated from bone marrow samples.

Toxicity will be evaluated by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

MRD Negativity using bone marrow and blood samples

Spots Global Cancer Trial Database for A Study of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly-Diagnosed Multiple Myeloma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial