NCT02597062

High-Dose Weekly Carfilzomib Plus Cyclophosphamide and Dexamethasone in the Treatment of Relapsed Multiple Myeloma

Completed Phase 2 Results posted Last updated 28 August 2023

What this trial tests

Phase 2 trial testing Carfilzomib in Multiple Myeloma in 76 participants. Completed in 1 February 2022.

Timeline

5 July 2016

Primary endpoint
19 June 2019

1 February 2022

Quick facts

Lead sponsor	Canadian Cancer Trials Group
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	76
Start date	5 July 2016
Primary completion	19 June 2019
Estimated completion	1 February 2022
Sites	9 locations across Canada

Drugs / interventions tested

• Carfilzomib (carfilzomib) — full drug profile →
• Cyclophosphamide (cyclophosphamide) — full drug profile →
• Dexamethasone (dexamethasone) — full drug profile →

Conditions studied

• Multiple Myeloma — all drugs for Multiple Myeloma →

Sponsor

Canadian Cancer Trials Group — full company profile →

Who can join

18 and older, any sex, with Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate After 4 Cycles Primary · 4 months

Response rate to protocol treatment after 4 cycles is define by stringent complete response, complete response, partial response, very good partial response, minimal response. Complete response: Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow biopsy Stringent complete response: Complete response plus Absence of clonal cells in bone marrow d by immunohistochemistry or immunofluorescence Very good partial response: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% redu

Group	Value	95% CI
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone	4
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone	3
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone	32
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone	21

Progression-free Survival Secondary · 3 years

Median time to progression or death assessed by biochemistry, radiology and immunology tests will be reported. Progression is evaluated in this study using the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) with any one or more of the following: 1. Increase of ≥ 25% from lowest response value in: Serum M-component and/or Urine M-component and/or Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels or Bone marrow plasma cell percentages. 2. Definite development of new bone lesions or soft tissu

Group	Value	95% CI
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone	17.15	13.57 – 21.49

Overall Survival Secondary · 3 years

Median time to death in months will be reported

Group	Value	95% CI
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone	27.43	22.05 – 33.8

Adverse events — posted to ClinicalTrials.gov

Time frame: 3 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Carfilzomib Plus Cyclophosphamide Plus Dexamethasone

Serious: 39/75 (52%)

Deaths: 31/75

Serious adverse events (34 terms)

Reaction	System	Carfilzomib Plus Cyclophos…
Lung infection	Infections and infestations	—
Fever	General disorders	—
Sepsis	Infections and infestations	—
Febrile neutropenia	Blood and lymphatic system disorders	—
Upper respiratory infection	Infections and infestations	—
Alanine aminotransferase increased	Investigations	—
Aspartate aminotransferase increased	Investigations	—
Thrombotic thrombocytopenic purpura	Blood and lymphatic system disorders	—
Heart failure	Cardiac disorders	—
Non-cardiac chest pain	General disorders	—
Thromboembolic event	Vascular disorders	—
Other blood and lymphatic system disorders	Blood and lymphatic system disorders	—
Mitral valve disease	Cardiac disorders	—
Right ventricular dysfunction	Cardiac disorders	—
Death NOS	General disorders	—
Fatigue	General disorders	—
Malaise	General disorders	—
Abdominal infection	Infections and infestations	—
Device related infection	Infections and infestations	—
Other infections and infestations	Infections and infestations	—
Ankle fracture	Injury, poisoning and procedural complications	—
Fracture	Injury, poisoning and procedural complications	—
Blood bilirubin increased	Investigations	—
Dehydration	Metabolism and nutrition disorders	—
Bone pain	Musculoskeletal and connective tissue disorders	—

Other adverse events (5 terms — click to expand)

Reaction	System	Carfilzomib Plus Cyclophos…
Lung infection	Infections and infestations	—
Fatigue	General disorders	—
Hypertension	Vascular disorders	—
Sepsis	Infections and infestations	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—

Most-reported serious reactions: Lung infection, Fever, Sepsis, Febrile neutropenia, Upper respiratory infection, Alanine aminotransferase increased, Aspartate aminotransferase increased, Thrombotic thrombocytopenic purpura.

Data from ClinicalTrials.gov NCT02597062 adverse events section.

Sponsor's own description

The purpose of this study is to find out what effects carfilzomib has on relapsed multiple myeloma when administered in combination with cyclophosphamide and dexamethasone.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Drug-induced Thrombotic Microangiopathy with Concurrent Proteasome Inhibitor Use in the Treatment of Multiple Myeloma: A Case Series and Review of the Literature.
   Monteith BE, Venner CP, Reece DE, Kew AK, et al · · 2020 · cited 8× · PMID 32807717 · DOI 10.1016/j.clml.2020.04.014