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A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT02195479
Recruitment Status : Active, not recruiting
First Posted : July 21, 2014
Last Update Posted : March 22, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to determine if the addition of daratumumab to velcade (bortezomib) melphalan-prednisone (VMP) will prolong progression-free survival (PFS) compared with VMP alone in participants with previously untreated multiple myeloma who are ineligible for high dose chemotherapy and autologous stem cell transplant (ASCT).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Velcade Drug: Melphalan Drug: Prednisone Drug: Daratumumab Drug: Dexamethasone Phase 3

Detailed Description:
The study consists of 3 phases: Screening Phase (within 21 days prior to randomization), Treatment Phase (Cycle 1 Day 1 to discontinuation of all study treatment), and Follow-up Phase (from discontinuation of all study treatment up to death, lost to follow up, withdrawal of consent, or the study ends, whichever occurs first). Treatment phase will include 2 treatments (Treatment A: participants will receive Velcade MelphalanPrednisone (VMP) alone and Treatment B: participants will receive daratumumab in combination with VMP).Two interim analyses are planned. The first will be to evaluate safety after a total of approximately 100 participants have been treated for at least 2 cycles or discontinued the study treatment. The second will be to evaluate cumulative interim safety and efficacy data, and will be performed when approximately 216 PFS events have been accumulated. The maximum duration of the study will be 5 years after the last participant is randomized or after 330 participants have died, whichever comes first. Efficacy will be primarily measured by comparison of PFS between the two treatment arms. Participants' safety will be monitored throughout the study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 706 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Controlled, Open-label Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy
Actual Study Start Date : December 9, 2014
Actual Primary Completion Date : November 21, 2017
Estimated Study Completion Date : October 20, 2021


Arm Intervention/treatment
Active Comparator: Treatment Arm A (VMP Alone)
Participants will receive velcade (bortezomib) 1.3 milligram per square meter (mg/m^2) as subcutaneous injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m^2 , orally, once daily (on Days 1-4) and prednisone 60 mg/m^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9.
Drug: Velcade
Participants will receive velcade 1.3 mg/m^2, as subcutaneous injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9.

Drug: Melphalan
Participants will receive melphalan 9 mg/m^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9.

Drug: Prednisone
Participants will receive prednisone 60 mg/m^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9.

Experimental: Treatment Arm B (D-VMP)
Participants will receive velcade 1.3 mg/m^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m^2, orally, once daily (on Days 1-4) and prednisone 60 mg/m^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9. In addition participants will also receive daratumumab 16 mg/kg as IV infusion, once weekly, for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On days when daratumumab is given, dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute, and prednisone 60 mg/m2 once daily will be given on Days 2-4.
Drug: Velcade
Participants will receive velcade 1.3 mg/m^2, as subcutaneous injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9.

Drug: Melphalan
Participants will receive melphalan 9 mg/m^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9.

Drug: Prednisone
Participants will receive prednisone 60 mg/m^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9.

Drug: Daratumumab
Participants will receive daratumumab 16 mg/kg as intravenous infusion, once weekly, for 6 weeks in Cycle 1 and then once every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end.

Drug: Dexamethasone
Participants administered with dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute.




Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Assess at approximately 41 months from randomization ]
    The PFS is defined as time from date of randomization to either progressive disease (PD), or death, whichever occurs first. PD will be determined according to International Myeloma Working Group (IMWG) criteria.


Secondary Outcome Measures :
  1. Time to Disease Progression (TTP) [ Time Frame: Assess at approximately 41 months from randomization ]
    The TTP is defined as the time from the date of randomization to the date of first documented evidence of PD as defined by IMWG criteria.

  2. Complete Response (CR) [ Time Frame: Assess at approximately 41 months from randomization ]
    Percentage of participants with CR, as defined by the IMWG criteria.

  3. Minimal Residual Disease (MRD) Negativity Rate [ Time Frame: Assess at approximately 41 months from randomization ]
    MRD negativity rate, defined as the proportion of participants who have negative MRD at any time point after the date of randomization.

  4. Progression Free Survival on Next Line of Therapy (PFS2) [ Time Frame: Assess at approximately 41 months from randomization ]
    The PFS2 is defined as the time from randomization to disease progression on the next line of treatment or death, whichever comes first. Disease progression will be based on Investigator judgment.

  5. Time to Next Treatment [ Time Frame: Assess at approximately 41 months from randomization ]
    Time to next treatment is defined as the time from randomization to the start of the next-line treatment.

  6. Overall Response Rate (ORR) [ Time Frame: Assess at approximately 41 months from randomization ]
    The ORR is defined as the proportion of participants who achieve PR or better according to IMWG criteria, during or after study treatment.

  7. Stringent Complete Response (sCR) [ Time Frame: Assess at approximately 41 months from randomization ]
    The sCR rate is defined as the percentage of participants with sCR, as defined by the IMWG criteria.

  8. Very Good Partial Response (VGPR) or Better [ Time Frame: Assess at approximately 41 months from randomization ]
    The VGPR or better rate, defined as the proportion of participants achieving VGPR and CR (including sCR) according to the IMWG criteria during or after the study treatment.

  9. Time to Response [ Time Frame: Assess at approximately 41 months from randomization ]
    Time to response, defined as the time between randomization and the first efficacy evaluation that the participant has met all criteria for PR or better.

  10. Duration of Response [ Time Frame: Assess at approximately 41 months from randomization ]
    Duration of response is time from the date of initial documentation of response (PR or better) to the date of first documented evidence of PD, as defined by IMWG criteria.

  11. Overall Survival (OS) [ Time Frame: Assess at approximately 41 months after first participant randomized up to a maximum of 5 years after last participant is dosed ]
    The OS is defined as the time from the date of randomization to the date of the participant's death.

  12. Impact of D-VMP compared to VMP on patient-reported perception of global health. [ Time Frame: Assess at approximately 41 months from randomization ]
    The EORTC-QLQ-C30, EQ-5D-5L is a generic measure of health status which is a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).

  13. Clinical efficacy of D-VMP in high risk molecular subgroups compared to VMP alone. [ Time Frame: Assess at approximately 41 months from randomization ]
    Clinical efficacy will be compared in high risk molecular subgroups between DVMP and VMP.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant must have documented multiple myeloma satisfying the calcium elevation, renal insufficiency, anemia, and bone abnormalities (CRAB) diagnostic criteria, monoclonal plasma cells in the bone marrow greater than or equal to 10 percent (%) or presence of a biopsy proven plasmacytoma, and measurable secretory disease, as assessed by the central laboratory, and defined in protocol
  • Participants who are newly diagnosed and not considered candidate for high-dose chemotherapy with stem cell transplantation (SCT) due to: being age >=65 years, or in participants <65 years: presence of important comorbid conditions likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation
  • Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Meet the clinical laboratory criteria as specified in the protocol
  • A woman of childbearing potential must have a negative serum pregnancy test at screening within 14 days prior to randomization
  • Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin prior to dosing. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy

Exclusion Criteria:

  • Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma
  • Participant has a diagnosis of Waldenstrom's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
  • Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids before treatment
  • Participant has peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 4
  • Participant has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)
  • Participant has had radiation therapy within 14 days of randomization
  • Participant has had plasmapheresis within 28 days of randomization
  • Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second [FEV1] <50% of predicted normal), known moderate or severe persistent asthma within the last 2 years or currently has uncontrolled asthma of any classification (controlled intermittent asthma or controlled mild persistent asthma is allowed)
  • Participants with known or suspected COPD must have a FEV1 test during screening
  • Participant is known to be seropositive for human immunodeficiency virus (HIV), known to have hepatitis B surface antigen positivity, or history of to have a history of hepatitis C
  • Participant has any concurrent medical or psychiatric condition or disease (example active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02195479


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Locations
United States, California
California City, California, United States
Corona, California, United States
Fountain Valley, California, United States
Los Angeles, California, United States
United States, Florida
Hialeah, Florida, United States
Orange Park, Florida, United States
United States, Illinois
Chicago, Illinois, United States
United States, Missouri
Springfield, Missouri, United States
United States, Ohio
Cleveland, Ohio, United States
United States, Virginia
Fredericksburg, Virginia, United States
Argentina
Buenos Aires, Argentina
Ciudad Autonoma Buenos Aires, Argentina
Córdoba, Argentina
Santa Fe, Argentina
Australia
Adelaide, Australia
Bendigo, Australia
Camperdown N/A, Australia
Geelong, Australia
Gosford, Australia
Greenslopes, Australia
Hobart, Australia
North Adelaide, Australia
Parkville, Australia
Belgium
Antwerpen, Belgium
Antwerp, Belgium
Brussel, Belgium
Charleroi, Belgium
Gent, Belgium
Kortrijk, Belgium
Liege, Belgium
Turnhout, Belgium
Yvoir, Belgium
Brazil
Barretos, Brazil
Cuiaba - Mount, Brazil
Fortaleza Ceara, Brazil
Fortaleza, Brazil
Goiânia, Brazil
Natal, Brazil
Niteroi N/A, Brazil
Porto Alegre, Brazil
Riberao Preto, Brazil
Sao Paulo, Brazil
Bulgaria
Pleven, Bulgaria
Plovdiv, Bulgaria
Sofia, Bulgaria
Varna, Bulgaria
Vratsa, Bulgaria
Croatia
Zadar, Croatia
Zagreb, Croatia
Czechia
Brno, Czechia
Hradec Kralove, Czechia
Olomouc, Czechia
Ostrava-Poruba, Czechia
Praha 10, Czechia
Praha 2, Czechia
Georgia
Tbilisi, Georgia
Germany
Berlin, Germany
Dortmund, Germany
Karlsruhe, Germany
Potsdam, Germany
Saarbrücken, Germany
Stuttgart, Germany
Würzburg, Germany
Greece
Athens Attica, Greece
Athens, Greece
Patra, Greece
Thessaloniki, Greece
Hungary
Budapest, Hungary
Debrecen, Hungary
Kaposvar, Hungary
Pecs N/A, Hungary
Japan
Chiba, Japan
Hitachi, Japan
Kanazawa, Japan
Kawasaki, Japan
Kobe, Japan
Kurume, Japan
Matsuyama, Japan
Nagoya, Japan
Narita, Japan
Ohgaki, Japan
Okayama, Japan
Osaka, Japan
Sendai, Japan
Shibukawa, Japan
Tachikawa, Japan
Tokyo, Japan
Toyohashi, Japan
Korea, Republic of
Busan, Korea, Republic of
Gyeonggi-Do, Korea, Republic of
Incheon, Korea, Republic of
Jeonnam, Korea, Republic of
Seongnam, Korea, Republic of
Seoul, Korea, Republic of
Macedonia, The Former Yugoslav Republic of
Skopje, Macedonia, The Former Yugoslav Republic of
Poland
Bialystok, Poland
Bydgoszcz, Poland
Chorzow, Poland
Gdansk, Poland
Legnica, Poland
Lublin, Poland
Opole, Poland
Slupsk, Poland
Warszawa Ul, Poland
Warszawa, Poland
Wroclaw, Poland
Portugal
Lisboa, Portugal
Lisbon, Portugal
Porto, Portugal
Romania
Brasov, Romania
Bucharest, Romania
Iasi, Romania
Russian Federation
Arkhangelsk, Russian Federation
Dzerzhinsk, Russian Federation
Ekaterinbourg, Russian Federation
Nizhny Novgorod, Russian Federation
Ryazan, Russian Federation
Saint-Petersburg, Russian Federation
Saratov, Russian Federation
Sochi, Russian Federation
St Petersburg, Russian Federation
Volgograd, Russian Federation
Serbia
Belgrade, Serbia
Nis, Serbia
Novi Sad, Serbia
Sremska Kamenica, Serbia
Zemun, Serbia
Spain
Andalucía, Spain
Badalona, Spain
Barcelona, Spain
Córdoba, Spain
Girona, Spain
La Laguna, Spain
Madrid, Spain
Maranon, Spain
Murcia N/A, Spain
Ourense, Spain
Pamplona, Spain
Salamanca, Spain
Sevilla, Spain
Toledo, Spain
Valencia, Spain
Zaragoza, Spain
Turkey
Altindag, Turkey
Ankara, Turkey
Aydin, Turkey
Izmir, Turkey
Kayseri, Turkey
Samsun, Turkey
Tekirdag, Turkey
Ukraine
Cherkassy, Ukraine
Dnepropetrovsk, Ukraine
Ivano-Frankivsk, Ukraine
Kharkov, Ukraine
Khmelnitskiy, Ukraine
Lviv, Ukraine
Zaporizhzhia, Ukraine
United Kingdom
Birmingham, United Kingdom
Cambridge, United Kingdom
Colchester, United Kingdom
Harlow, United Kingdom
Leicester, United Kingdom
London, United Kingdom
Manchester, United Kingdom
Woolwich, United Kingdom
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02195479     History of Changes
Other Study ID Numbers: CR104761
54767414MMY3007 ( Other Identifier: Janssen Research and Development, LLC )
2014-002272-88 ( EudraCT Number )
First Posted: July 21, 2014    Key Record Dates
Last Update Posted: March 22, 2018
Last Verified: March 2018

Keywords provided by Janssen Research & Development, LLC:
Multiple Myeloma
Bortezomib
Velcade
Melphalan
Prednisone
Daratumumab

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Prednisone
Daratumumab
Bortezomib
Melphalan
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones