ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03158688
Previous Study | Return to List | Next Study

Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. (CANDOR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03158688
Recruitment Status : Active, not recruiting
First Posted : May 18, 2017
Last Update Posted : October 24, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
Compare carfizomib, dexamethasone, and daratumumab (KdD) to Carfilzomib and dexamethasone (Kd) in terms of progression free survival (PFS) in patients with multiple myeloma who have relapsed after 1 to 3 prior therapies.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Multiple Myeloma Drug: Dexamethasone Drug: Daratumumab Drug: Carfilzomib Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 466 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Phase 3 Study Comparing Carfilzomib, Dexamethasone, and Daratumumab to Carfilzomib and Dexamethasone for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma CANDOR Study of Carfilzomib ANd Daratumumab fOr Relapsed Myeloma
Actual Study Start Date : June 13, 2017
Estimated Primary Completion Date : May 24, 2019
Estimated Study Completion Date : July 21, 2022


Arm Intervention/treatment
Active Comparator: Arm 2 - Carfilzomib and Dexamethasone

Carfilzomib will be dosed twice weekly as an intravenous (IV) infusion and Dexamethasone will be taken orally or by IV infusion weekly. The IV administration of dexamethasone must be given on carfilzomib IV infusion days. The required order of administrationon Arm 2 is as follows: dexamethasone then carfilzomib.

For days when dexamethasone is given in the absence of carfilzomib IV infusion, it may be given orally (PO).

Drug: Dexamethasone
Dexamethasone 40 mg will be taken orally or by IV infusion weekly. The IV administration of dexamethasone must be given on carfilzomib and/or daratumumab IV infusion days. Dexamethasone IV will be given on successive days at a split dose of 20 mg each treatment day on weeks with carfilzomib and/or daratumumab infusions. All subjects regardless of age will be required to receive 20 mg of dexamethasone on days 1 and 2 of cycle 1 (as a preinfusion medication for daratumumab infusion) followed by 20 mg of methylprednisolone or equivalent on the third day.

Drug: Carfilzomib

Carfilzomib will be administered as an intravenous (IV) infusion. On days when more than 1 investigational product is administered, the required order of administration is as follows: dexamethasone, pre-infusion medications for daratumumab, carfilzomib, daratumumab, and post infusion medications for daratumumab.

Carfilzomib will be dosed twice weekly over 30 ± 5 minutes, on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. The administration may be within ± 2 days for each scheduled dose. The dose will be 20 mg/m2 on cycle 1 days 1 and 2 and 56 mg/m2 beginning on cycle 1 day 8 and thereafter.

Each subject's first dose of carfilzomib will be calculated based upon baseline body surface area (BSA). Dose should be capped based on a BSA of 2.2 m2.


Active Comparator: Arm 1 - Carfilzomib, Dexamethasone and Daratumumab
Carfilzomib will be dosed twice weekly as an intravenous (IV) infusion. Daratumumab will be administered as an IV infusion - on days 1 and 2 of cycle 1 at 8 mg/kg dose each day; then at 16 mg/kg dose once weekly as a single infusion for the remaining doses of the first 2 cycles; then every 2 weeks for 4 cycles (cycles 3 to 6), and then every 4 weeks for the remaining cycles or until disease progression. Dexamethasone 40 mg will be taken orally or by IV infusion weekly. The IV administration of dexamethasone must be given on carfilzomib and/or daratumumab IV infusion days. On days when more than 1 investigational product is administered, the required order of administration is as follows: dexamethasone, pre-infusion medications for daratumumab, carfilzomib, daratumumab, and post-infusion medications for daratumumab.
Drug: Dexamethasone
Dexamethasone 40 mg will be taken orally or by IV infusion weekly. The IV administration of dexamethasone must be given on carfilzomib and/or daratumumab IV infusion days. Dexamethasone IV will be given on successive days at a split dose of 20 mg each treatment day on weeks with carfilzomib and/or daratumumab infusions. All subjects regardless of age will be required to receive 20 mg of dexamethasone on days 1 and 2 of cycle 1 (as a preinfusion medication for daratumumab infusion) followed by 20 mg of methylprednisolone or equivalent on the third day.

Drug: Daratumumab
Daratumumab will be administered as an IV infusion. On days 1 and 2 of cycle 1, daratumumab will be administered at a split-dose of 8 mg/kg in 500 mL normal saline. The dose of 16 mg/kg in 500 mL normal saline will be given once weekly as a single infusion for the remaining doses of the first 2 cycles (ie, days 8, 15, and 22 of cycle 1; and days 1, 8, 15, and 22 of cycle 2), then every 2 weeks for 4 cycles (cycles 3 to 6), and then every 4 weeks for the remaining cycles or until disease progression. The administration may be within ± 2 days for each scheduled dose.

Drug: Carfilzomib

Carfilzomib will be administered as an intravenous (IV) infusion. On days when more than 1 investigational product is administered, the required order of administration is as follows: dexamethasone, pre-infusion medications for daratumumab, carfilzomib, daratumumab, and post infusion medications for daratumumab.

Carfilzomib will be dosed twice weekly over 30 ± 5 minutes, on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. The administration may be within ± 2 days for each scheduled dose. The dose will be 20 mg/m2 on cycle 1 days 1 and 2 and 56 mg/m2 beginning on cycle 1 day 8 and thereafter.

Each subject's first dose of carfilzomib will be calculated based upon baseline body surface area (BSA). Dose should be capped based on a BSA of 2.2 m2.





Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 28 months ]
    Compare carfilzomib, dexamethasone, and daratumumab (KdD) to carfilzomib and dexamethasone (Kd) in terms of progression free survival (PFS) in patients with multiple myeloma who have relapsed after 1 to 3 prior therapies.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 28 Months ]
    Overall Response Rate (ORR; defined as the proportion of best overall response of stringent complete response [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]).

  2. Rate of minimal residual disease negative-complete response [ Time Frame: 12 Months ]
    Rate of minimal residual disease negative-complete response (MRD[-]CR) in bone marrow aspirates at 12 months (± 4 weeks) as determined by Next-Generation sequencing (NGS).

  3. Duration of response (DOR) [ Time Frame: 28 Months ]
  4. Overall survival (OS) [ Time Frame: 28 Months ]
  5. Time to next treatment [ Time Frame: 28 Months ]
  6. time to progression (TTP) [ Time Frame: 28 Months ]
  7. Time to response [ Time Frame: 28 Months ]
  8. Persistence of MRD[-]CR [ Time Frame: 28 Months ]
  9. Complete response rate (CRR) [ Time Frame: 28 Months ]
  10. MRD[-] rate [ Time Frame: 12 Months ]
    MRD[-]CR rate, MRD[-]CR defined as achievement of CR by IRC per International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) and MRD[-] status as assessed by NGS (at a 10-5 level, pending analytical validation) at 12 months

  11. Quality of life questionnaire - core 30 items [ Time Frame: 28 Months ]
    Quality of life questionnaire - core 30 items (QLQ-C30).

  12. Quality of Life (QoL) measured by European Organization [ Time Frame: 28 Months ]
    Quality of Life (QoL) measured by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 version 3 questionnaire.

  13. Subject incidence of treatment-emergent adverse events [ Time Frame: 28 Months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Criteria 1 Relapsed or progressive multiple myeloma after last treatment
  • Criteria 2 Males or females ≥ 18 years of age
  • Criteria 3 Measurable disease with at least 1 of the following assessed within 21 days prior to randomization:

    • IgG multiple myeloma: serum monoclonal paraprotein (M-protein) level

      • 1.0 g/dL,
    • IgA, IgD, IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL,
    • urine M-protein ≥ 200 mg/24 hours,
    • in subjects without measurable serum or urine M- protein, serum free light chain (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio
  • Criteria 4 Received at least 1 but not more than 3 prior lines of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy, see Appendix E for guidance)
  • Criteria 5 Prior therapy with carfilzomib is allowed as long as the patient had at least a PR to most recent therapy with carfilzomib, was not removed due to toxicity, did not relapse within 60 days from discontinuation of carfilzomib, and will have at least a 6-month carfilzomib treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not proteasome inhibitors or CD38 antibodies during this 6-month carfilzomib treatment free interval)
  • Criteria 6 Prior therapy with anti-CD38 antibodies is allowed as long as the patient had at least a PR to most recent therapy with CD38 antibody, was not removed due to toxicity, did not relapse within 60 days from intensive treatment (at least every other week) of CD38 antibody therapy, and will have at least a 6 month CD38 antibody treatment-free interval from last dose received until first study treatment
  • Other inclusion criteria may apply

Exclusion Criteria:

  • Criteria 1 Waldenström macroglobulinemia
  • Criteria 2 Multiple myeloma of IgM subtype
  • Criteria 3 POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Criteria 4 Plasma cell leukemia (> 2.0 x 109/L circulating plasma cells by standard differential)
  • Criteria 5 Myelodysplastic syndrome
  • Criteria 6 Known moderate or severe persistent asthma within the past 2 years
  • Criteria 7 Known chronic obstructive pulmonary disease (COPD) with a FEV1 < 50% of predicted normal
  • Criteria 8 Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT interval (QTc) of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to randomization
  • Other exclusion criteria may apply

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): NCT03158688


  Hide Study Locations
Locations
United States, Florida
Research Site
Boca Raton, Florida, United States, 33486
United States, Georgia
Research Site
Atlanta, Georgia, United States, 30322
United States, Illinois
Research Site
Chicago, Illinois, United States, 60637-6613
United States, Indiana
Research Site
Fort Wayne, Indiana, United States, 46845
United States, Mississippi
Research Site
Hattiesburg, Mississippi, United States, 39401
United States, New Jersey
Research Site
Hackensack, New Jersey, United States, 07601
United States, New York
Research Site
New York, New York, United States, 10021
United States, North Carolina
Research Site
Charlotte, North Carolina, United States, 28204
United States, Ohio
Research Site
Canton, Ohio, United States, 44718
United States, South Carolina
Research Site
Charleston, South Carolina, United States, 29414
United States, Texas
Research Site
Dallas, Texas, United States, 75246
Australia, New South Wales
Research Site
Liverpool, New South Wales, Australia, 2170
Research Site
St Leonards, New South Wales, Australia, 2065
Research Site
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Research Site
Herston, Queensland, Australia, 4029
Research Site
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Research Site
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Research Site
East Melbourne, Victoria, Australia, 3002
Research Site
Fitzroy, VIC, Victoria, Australia, 3065
Research Site
Geelong, Victoria, Australia, 3220
Research Site
Melbourne, Victoria, Australia, 3004
Austria
Research Site
Graz, Austria, 8036
Research Site
Salzburg, Austria, 5020
Belgium
Research Site
Antwerpen, Belgium, 2060
Research Site
Brussel, Belgium, 1090
Research Site
Charleroi, Belgium, 6000
Research Site
Gent, Belgium, 9000
Research Site
Leuven, Belgium, 3000
Bulgaria
Research Site
Plovdiv, Bulgaria, 4000
Research Site
Sofia, Bulgaria, 1431
Research Site
Sofia, Bulgaria, 1756
Canada, Alberta
Research Site
Calgary, Alberta, Canada, T2N 2T9
Research Site
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Research Site
Ottawa, Ontario, Canada, K1H 8L6
Research Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H1T 2M4
Czechia
Research Site
Brno, Czechia, 625 00
Research Site
Hradec Kralove, Czechia, 500 05
Research Site
Ostrava-Poruba, Czechia, 708 52
Research Site
Plzen, Czechia, 304 60
Research Site
Praha 2, Czechia, 128 08
France
Research Site
La Roche Sur Yon Cedex 9, France, 85925
Research Site
Le Chesnay cedex, France, 78157
Research Site
Lille Cedex, France, 59037
Research Site
Nantes Cedex 1, France, 44093
Research Site
Pessac Cedex, France, 33604
Research Site
Pierre-Benite cedex, France, 69495
Research Site
Poitiers Cedex, France, 86021
Research Site
Vandoeuvre les Nancy, France, 54511
Greece
Research Site
Athens, Greece, 10676
Research Site
Athens, Greece, 11528
Research Site
Patra, Greece, 26504
Research Site
Thessaloniki, Greece, 54007
Hungary
Research Site
Budapest, Hungary, 1097
Research Site
Budapest, Hungary, 1125
Research Site
Debrecen, Hungary, 4032
Research Site
Gyula, Hungary, 5700
Research Site
Szeged, Hungary, 6725
Japan
Research Site
Nagoya-shi, Aichi, Japan, 467-8602
Research Site
Toyohashi-shi, Aichi, Japan, 441-8570
Research Site
Kamogawa-shi, Chiba, Japan, 296-8602
Research Site
Fukuoka-shi, Fukuoka, Japan, 811-1395
Research Site
Fukuoka-shi, Fukuoka, Japan, 812-8582
Research Site
Ogaki-shi, Gifu, Japan, 503-8502
Research Site
Maebashi-shi, Gunma, Japan, 371-8511
Research Site
Shibukawa-city, Gunma, Japan, 377-0280
Research Site
Kyoto-shi, Kyoto, Japan, 602-8566
Research Site
Niigata-shi, Niigata, Japan, 951-8566
Research Site
Okayama-shi, Okayama, Japan, 701-1192
Research Site
Suita-shi, Osaka, Japan, 565-0871
Research Site
Kawagoe-shi, Saitama, Japan, 350-8550
Research Site
Utsunomiya-shi, Tochigi, Japan, 320-0834
Research Site
Tokushima-shi, Tokushima, Japan, 770-8539
Research Site
Koto-ku, Tokyo, Japan, 135-8550
Research Site
Shibuya-ku, Tokyo, Japan, 150-8935
Korea, Republic of
Research Site
Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
Research Site
Hwasun, Jeollanam-do, Korea, Republic of, 58128
Research Site
Seoul, Korea, Republic of, 03080
Research Site
Seoul, Korea, Republic of, 03722
Research Site
Seoul, Korea, Republic of, 05505
Research Site
Seoul, Korea, Republic of, 06351
Research Site
Seoul, Korea, Republic of, 06591
Poland
Research Site
Bialystok, Poland, 15-732
Research Site
Chorzow, Poland, 41-500
Research Site
Lublin, Poland, 20-090
Research Site
Poznan, Poland, 60-569
Research Site
Warszawa, Poland, 02-776
Research Site
Wroclaw, Poland, 50-367
Romania
Research Site
Brasov, Romania, 500152
Research Site
Bucharest, Romania, 030171
Research Site
Bucharest, Romania, 050098
Research Site
Bucuresti, Romania, 020125
Research Site
Bucuresti, Romania, 022328
Research Site
Cluj-Napoca, Romania, 400124
Research Site
Craiova, Romania, 200143
Russian Federation
Research Site
Nizhny Novgorod, Russian Federation, 603126
Research Site
Petrozavodsk, Russian Federation, 185019
Research Site
Samara, Russian Federation, 443079
Research Site
Saratov, Russian Federation, 410028
Spain
Research Site
Salamanca, Castilla León, Spain, 37007
Research Site
Badalona, Cataluña, Spain, 08916
Research Site
Barcelona, Cataluña, Spain, 08036
Research Site
Pamplona, Navarra, Spain, 31008
Research Site
Madrid, Spain, 28041
Taiwan
Research Site
Changhua, Taiwan, 50006
Research Site
Tainan, Taiwan, 70403
Research Site
Taipei, Taiwan, 10002
Research Site
Taipei, Taiwan, 11217
Turkey
Research Site
Ankara, Turkey, 06100
Research Site
Ankara, Turkey, 06590
Research Site
Izmir, Turkey, 35040
Research Site
Samsun, Turkey, 55139
United Kingdom
Research Site
Leeds, United Kingdom, LS9 7TF
Research Site
London, United Kingdom, NW1 2PG
Research Site
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03158688     History of Changes
Other Study ID Numbers: 20160275
2016-003554-33 ( EudraCT Number )
First Posted: May 18, 2017    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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
Daratumumab
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents