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

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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


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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