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

NCT02597062 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MYX1MCRN003
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate After 4 Cycles

  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% reduction in serum M-protein with urine M-protein level \<100 mg/24 hours. Partial response: ≥50% reduction in serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 hours Minimal response: 25-49% reduction in serum M-protein, and 50-89% reduction in 24-hour urinary M-protein, if ≥ 200 mg/24 hours at baseline

  4 months

Secondary Outcomes (2)

• Progression-free Survival

  3 years

• Overall Survival

  3 years

Study Arms (1)

Carfilzomib plus cyclophosphamide plus dexamethasone

EXPERIMENTAL

20 mg/m2 day 1 of first cycle then escalated to 70 mg/m2 for all subsequent doses) given on days 1, 8, and 15 of a 28 day cycle plus weekly oral dexamethasone (\< 70 years, 40 mg; ≥ 70 years 20mg) and cyclophosphamide 300 mg/m2 capped at 500 mg

Drug: Carfilzomib; Drug: Cyclophosphamide; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Carfilzomib plus cyclophosphamide plus dexamethasone

Cyclophosphamide DRUG

Carfilzomib plus cyclophosphamide plus dexamethasone

Dexamethasone DRUG

Carfilzomib plus cyclophosphamide plus dexamethasone

Eligibility Criteria

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

You may qualify if:

• Relapsed symptomatic multiple myeloma as per the International Myeloma Working group criteria \[Palumbo 2009\].
• Measurable disease, as defined by one or more of the following (assessed within 21 days prior to registration):
• Serum M-protein ≥ 5 g/L (0.5g/dL)
• Urine Bence-Jones protein ≥ 200 mg/24 hours
• Involved serum free light chain (FLC) measurement ≥ 100 mg/L (10 mg/dL), provided serum FLC ratio is abnormal (abnormal if FLC ratio is \<0.26 or \>1.65)
• Biopsy proven plasmacytoma
• For IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) ≥ 750 mg/dL (0.75 g/dL)
• Prior treatment with at least one, but no more than three, regimens for multiple myeloma

You may not qualify if:

• Achieved a response to at least one prior regimen (defined as ≥ 25% decrease in M-protein)
• Age ≥ 18 years.
• Life expectancy ≥ 3 months.
• ECOG performance status 0-2.
• Laboratory Requirements (must be done within 21 days of registration):
• Hematology:
• Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L
• Hemoglobin ≥ 8 g/dL (80 g/L) (subjects may be receiving red blood cell (RBC) transfusions in accordance with institutional guidelines)
• Platelet count ≥ 50 × 10\^9/L, independent of platelet transfusions for 7 days. (≥ 30 × 10\^9/L if myeloma involvement in the bone marrow is ≥ 50%)
• Biochemistry:
• ALT ≤ 3.5 x UNL
• Serum direct bilirubin ≤ 2 mg/dL (34 μmol/L) (only required if total bilirubin ≥ 2mg/dL (34μmol/L)
• Creatinine clearance (CrCl) ≥ 30 mL/minute (Crockcroft and Gault formula) and not on dialysis.
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
• Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Amgen: collaborator
• Canadian Myeloma Research Group: collaborator

Study Sites (9)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Regional Health Authority B, Zone 2

Saint John, New Brunswick, E2L 4L2, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

CIUSSS de l'Est-de-I'lle-de-Montreal

Montreal, Quebec, H1T 2M4, Canada

Location

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

Related Publications (2)

• Venner CP, LeBlanc R, Sandhu I, White D, Belch AR, Reece DE, Chen C, Dolan S, Lalancette M, Louzada M, Kew A, McCurdy A, Monteith B, Reiman T, McDonald G, Sherry M, Gul E, Chen BE, Hay AE. Weekly carfilzomib plus cyclophosphamide and dexamethasone in the treatment of relapsed/refractory multiple myeloma: Final results from the MCRN-003/MYX.1 single arm phase II trial. Am J Hematol. 2021 May 1;96(5):552-560. doi: 10.1002/ajh.26147.

  PMID: 33650179 RESULT

• Monteith BE, Venner CP, Reece DE, Kew AK, Lalancette M, Garland JS, Shepherd LE, Pater JL, Hay AE. Drug-induced Thrombotic Microangiopathy with Concurrent Proteasome Inhibitor Use in the Treatment of Multiple Myeloma: A Case Series and Review of the Literature. Clin Lymphoma Myeloma Leuk. 2020 Nov;20(11):e791-e800. doi: 10.1016/j.clml.2020.04.014. Epub 2020 Apr 30.

  PMID: 32807717 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Cyclophosphamide; 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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Bingshu Chen
• Organization: Canadian Cancer Trials Group

bechen@ctg.queensu.ca

613-533-6000

Study Officials

• Christopher Venner

  Cross Cancer Institute, Edmonton Alberta Canada

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 4, 2015
• Study Start: July 5, 2016
• Primary Completion: June 19, 2019
• Study Completion: February 1, 2022
• Last Updated: August 28, 2023
• Results First Posted: March 3, 2020

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (9)