A Study to Evaluate Dara-CyBorD in Previously Untreated and Relapsed Subjects With Multiple Myeloma

NCT02951819 | Completed Phase 2 Results

• 2 other identifiers: CR10823554767414MMY2012
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 26

Brief Summary

The purpose of this study is to evaluate complete response plus (+) very good partial response (CR+VGPR) rate following 4 cycles of induction therapy of daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD), in previously untreated subjects, and in relapsed subjects with multiple myeloma, as defined by the International Myeloma Working Group (IMWG) criteria.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Complete Response (CR) or Very Good Partial Response (VGPR)

  Percentage of participants who achieved CR or VGPR (as per International Myeloma Working Group \[IMWG\] criteria) was reported. CR: negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (\<) 5 percent (%) plasma cells (PC) in bone marrow. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (\>=) 90% reduction in serum M-protein plus urine M-protein level \< 100 milligram per 24 hours (mg/24hours).

  After 4 cycles of Induction (Approximately 4 months)

Secondary Outcomes (8)

• Overall Response Rate (ORR)

  After 4 Cycles of Induction (4 months), at End of Induction (4 to 8 months) and at the End of Maintenance (12 months)

• Time to Very Good Partial Response (VGPR) or Better

  Up to 36 months

• Time to Partial Response (PR) or Better

  Up to 12 months

• Duration of Response (DOR)

  Up to 36 months

• Progression Free Survival (PFS)

  Up to 36 months

Study Arms (1)

Dara-CyBorD

EXPERIMENTAL

Subjects will receive Daratumumab along with Cyclophosphamide, Bortezomib and Dexamethasone (Dara-CyBorD) as induction on a 28-day cycle length and Daratumab and Dexamethasone on Day 1 of each cycle for 12 cycles as maintenance therapy.

Drug: Daratumumab; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Daratumumab DRUG

For induction therapy cycle 1 day 1 and day 2 doses of daratumumab will be 8 milligram/kilogram (mg/kg). Starting cycle 1 week 2 until the completion of week 8 of daratumumab patients will receive 16 mg/kg Intravenously (IV) weekly. Starting week 9 until the completion of week 24 therapy daratumumab will be administered every other week at 16 mg/kg IV. Starting week 25 and beyond for induction therapy daratumumab will be given once every 4 weeks.

Dara-CyBorD

Cyclophosphamide DRUG

Subjects will receive 4 to 8 cycles of oral cyclophosphamide 300 milligram per meter square (mg/m\^2 ) on Days 1, 8, 15, and 22 for every 28 days.

Dara-CyBorD

Bortezomib DRUG

Subjects will receive 4 to 8 cycles of Bortezomib 1.5 mg/m2 subcutaneous (SC) on Days 1, 8, and 15 for every 28 days.

Dara-CyBorD

Dexamethasone DRUG

Subjects will be given corticosteroids (Dexamethasone) as pre-infusion therapy prior to daratumumab and for the first 8 cycles will also receive post-infusion corticosteroids (Dexamethasone).

Dara-CyBorD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with documented multiple myeloma (MM) as defined by the International Myeloma Working Group (IMWG) 2015 criteria: Clonal bone marrow plasma cells greater than or equal to (\>=) 10 percent (%) or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following CRAB (calcium level, renal dysfunction, anemia, and destructive bone lesions) features and myeloma defining events as in the protocol
• Subjects with previously untreated myeloma or relapsed myeloma with one prior line of therapy including an induction regimen which may be followed by autologous stem cell transplantation and single agent maintenance therapy. For previously untreated subjects an emergency course of steroids (defined as no greater than 40 milligram (mg) of dexamethasone, or equivalent per day for a maximum of 4 days) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• A woman of childbearing potential must have 2 negative serum (beta (β) human chorionic gonadotropin) or urine pregnancy tests during screening, the first one within 28 days prior to the first dose of study drug and the second within 24 hours prior to the first dose of study drug
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control example, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug

You may not qualify if:

• Refractory to any proteasome inhibitor (PI) or the combination of PI and immunomodulatory drug (IMiD) agents (such as lenalidomide), defined as failure to respond or progression within 60 days of the end of PI therapy
• Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma
• Has known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) less than (\<) 50 percent (%) of predicted normal
• Has known moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification
• Is known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C

Sponsors & Collaborators

• Janssen Scientific Affairs, LLC: lead

Study Sites (26)

Unknown Facility

Mobile, Alabama, United States

Location

Unknown Facility

Phoenix, Arizona, United States

Location

Unknown Facility

Sedona, Arizona, United States

Location

Unknown Facility

Tucson, Arizona, United States

Location

Unknown Facility

Fayetteville, Arkansas, United States

Location

Unknown Facility

Greenbrae, California, United States

Location

Unknown Facility

Denver, Colorado, United States

Location

Unknown Facility

Niles, Illinois, United States

Location

Unknown Facility

Indianapolis, Indiana, United States

Location

Unknown Facility

Louisville, Kentucky, United States

Location

Unknown Facility

Bethesda, Maryland, United States

Location

Unknown Facility

Columbia, Maryland, United States

Location

Unknown Facility

Grand Rapids, Michigan, United States

Location

Unknown Facility

Omaha, Nebraska, United States

Location

Unknown Facility

Camden, New Jersey, United States

Location

Unknown Facility

Albany, New York, United States

Location

Unknown Facility

East Setauket, New York, United States

Location

Unknown Facility

Fresh Meadows, New York, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Eugene, Oregon, United States

Location

Unknown Facility

Greenville, South Carolina, United States

Location

Unknown Facility

Austin, Texas, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Tyler, Texas, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

Related Publications (1)

• Yimer H, Melear J, Faber E, Bensinger WI, Burke JM, Narang M, Stevens D, Gray KS, Lutska Y, Bobba P, Qi K, Hoehn D, Qi M, Lin TS, Rifkin RM. Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for multiple myeloma: final results of the LYRA study. Leuk Lymphoma. 2022 Oct;63(10):2383-2392. doi: 10.1080/10428194.2022.2076847. Epub 2022 Jun 22.

  PMID: 35730586 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Cyclophosphamide; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Senior Director
• Organization: Janssen Scientific Affairs

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Scientific Affairs, LLC Clinical Trial

  Janssen Scientific Affairs, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2016
• First Posted: November 1, 2016
• Study Start: November 9, 2016
• Primary Completion: March 8, 2018
• Study Completion: August 17, 2020
• Last Updated: October 8, 2021
• Results First Posted: April 3, 2019

Record last verified: 2021-10

Locations

US (26)