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Multiple MyelomaPhase 2NCT03336073

Carfilzomib, Cyclophosphamide, Dexamethasone in Multiple Myeloma

A Phase 2 study testing Carfilzomib, Dexamethasone and cyclophosphamide in people with Multiple Myeloma, run by PETHEMA Foundation at 24 sites in Spain.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a multicenter, open label, phase II randomized controlled study that will evaluate the efficacy of carfilzomib and dexamethasone in combination with cyclophosphamide in R/R MM patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Carfilzomib, Dexamethasone and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
199 participants
Where
24 sitesSpain
Study dates
18 Dec 2017to Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years.
  • Performance status (ECOG) <2.
  • Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
  • Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
  • Patients previously diagnosed with MM according to the IMWG criteria (Lancet Oncology 2014) that after previous treatment with 1-3 regimens require therapy due to a relapse/progression of the disease.
  • Patients must have measurable disease, defined as follows:
Show all 9Show fewer
  • Serum monoclonal protein ≥ 0.5 g/L, or
  • Urine light-chain excretion of ≥ 0.2g /24 hours, or
  • Abnormal ratio of serum free light chains (FLCs) plus involved FLC level ≥100 mg/L.

Who cannot join

  • Primary refractory patients defined as not having achieved at least a PR with a prior therapy.
  • Refractoriness to prior proteasome inhibitor therapies, defined as not having achieved at least MR or having progressed under treatment or in the first 60 days after the last dose of the proteasome inhibitor.
  • Biochemical and haematological abnormalities as specified below:
  • Hemoglobin < 8.0 g/dL.
  • Platelet count <75x109/L without previous platelet transfusions in the last 7 days. If bone marrow infiltration is greater than 50%, a platelet count of ≥50x109/L is required.
  • Absolute neutrophil count (ANC) < 0.75 x109/L without G-CSF support in the last 7 days.
Show all 23Show fewer
  • Aspartate transaminase (AST): > 2.5 times the upper limit of normal.
  • Alanine transaminase (ALT): > 2.5 times the upper limit of normal.
  • Calculated or measured creatinine clearance: <30 mL/min (calculated from the Cockcroft and Gault formula, specified in Appendix C).
  • Left ventricle ejection fraction < 50%.
  • Absence of recovery from any significant non-haematological toxicity derived from previous treatments. The presence of alopecia and NCI-CTC grade < 2 symptomatic peripheral neuropathy is allowed.
  • Pregnant or breastfeeding women; men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, and oral contraception).
  • Previous history of any other neoplastic disease in the last five years (except basal cell carcinoma, skin epithelioma or carcinoma in situ of any site).
  • Other relevant diseases or adverse clinical conditions:
  • Congestive heart failure or angina pectoris, myocardial infarction within 12 months before inclusion in the study.
  • Uncontrolled arterial hypertension or cardiac arrhythmias (i.e. requiring a change in medication within the last 3 months or a hospital admission within the past 6 months).
  • History of significant neurological or psychiatric disorders.
  • Active infection
  • Significant non-neoplastic liver disease (e.g. cirrhosis, active chronic hepatitis).
  • Patient is known to be human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive or to suffer active hepatitis C infection
  • The patient has received concomitant anti-myeloma therapy within 14 days prior to Day 1 of Cycle 1.
  • Limit to the patient's ability to comply with the treatment or follow-up protocol.
  • Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

Spain24 sites

  • H.Universitari Germans Trias I Pujol de Badalona

    Barcelona

  • Hospital Clínic i Provincial de Barcelona

    Barcelona

  • Hospital de la Santa Creu i Sant Pau

    Barcelona

  • Ico L'Hospitalet

    Barcelona

  • Complejo Hospitalario de Cáceres

    Cáceres

  • Hospital de Cabueñes

    Gijón

  • Centro Hospitalario Universitario de Granada

    Granada

  • Hospital de León

    León

  • H. 12 de Octubre

    Madrid

  • H. Ramón y Cajal

    Madrid

  • Hospital Sanchinarro

    Madrid

  • Hospital Costa del Sol

    Málaga

  • Hospital Universitario Morales Meseguer

    Murcia

  • Hospital Virgn de la Arrixaca

    Murcia

  • Hospital Central de Asturias

    Oviedo

  • Hospital de Son Llàtzer

    Palma de Mallorca

  • Clinica Universitaria de Navarra

    Pamplona

  • Hospital Clínico Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitario de Canarias

    Santa Cruz de Tenerife, Canary Islands

  • Hospital Universitario de Santiago

    Santiago de Compostela

  • Hospital de Segovia

    Segovia

  • Complejo Hospitalario Regional Virgen Del Rocío

    Seville

  • Hospital de Toledo

    Toledo

  • Hospital Lozano Blesa

    Zaragoza

Other trials in Spain

About this study

Official title: Carfilzomib and Dexamethasone in Combination With Cyclophosphamide vs. Carfilzomib and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma: a Phase II Randomized Controlled Trial

This is a multicenter, open label, phase II randomized controlled study that will evaluate the efficacy of carfilzomib and dexamethasone in combination with cyclophosphamide in R/R MM patients.

For this purpose, R/R MM patients that have received 1-3 prior lines of therapy, and who are not primary refractory or refractory to proteasome inhibitors will be randomized to receive:

Read more
  • Experimental arm: carfilzomib at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) intravenously (iv) on days 1, 8, and 15, dexamethasone by mouth (po) at a dose of 20 mg (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16 and cyclophosphamide at a dose of 300 mg/m2 iv on days 1, 8 and 15, in 28 days cycles; or
  • Control arm: the same treatment but without cyclophosphamide.

Once the first 12 cycles are administered, treatment will be administered on days 1 and 15 of each cycle and the visit and doses on day 8 will be omitted in both study arms.

Patients older than 75 years will receive in both arms carfilzomib at a dose of 56 mg/m2 (20 mg/m2 only in the first infusion) during the cycles 1 and 2. If tolerability is acceptable, the dose could be increased up to 70 mg/m2 since the cycle 3.

Treatment will be continued until progression, unacceptable toxicity or investigator or patient decision.

Read the detailed description

Treatment will consist of 28-days cycles with:

  • Arm 1 (experimental arm):
  • Carfilzomib administered iv at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) iv on days 1, 8 and 15.
  • Dexamethasone at a dose of 20 mg po (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16.
  • Cyclophosphamide at a dose of 300 mg/m2 iv on days 1, 8 and 15
  • Arm 2 (control arm):
  • Carfilzomib administered iv at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) iv on days 1, 8, and 15.
  • Dexamethasone at a dose of 20 mg po (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16.

Once the first 12 cycles are administered, treatment will be administered on days 1 and 15 of each cycle and the visit and doses on day 8 will be omitted in both study arms.

Patients older than 75 years will receive in both arms carfilzomib at a dose of 56 mg/m2 (20 mg/m2 only in the first infusion) during the cycles 1 and 2. If tolerability is acceptable, the dose could be increased up to 70 mg/m2 since the cycle 3.

Treatments will be administered until progressive disease (PD) or unacceptable toxicity. Carfilzomib and cyclophosphamide will be provided by the sponsor. Dexamethasone may be utilized per a site's standard practice and will not be provided by the sponsor.

Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarfilzomibDrug

    carfilzomib at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) intravenously (iv) on days 1, 8, and 15

  • DexamethasoneDrug

    dexamethasone oral at a dose of 20 mg (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16

  • cyclophosphamideDrug

    cyclophosphamide at a dose of 300 mg/m2 iv on days 1, 8 and 15

Study groups in NCT03336073
Study groupRoleWhat they receive
carfilzomib, dexamethasone and cyclophosphamideExperimentalcarfilzomib at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) intravenously (iv) on days 1, 8, and 15, dexamethasone by mouth (po) at a dose of 20 mg (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16 and cyclophosphamide at a dose of 300 mg/m2 iv on days 1, 8 and 15, in 28 days cycles
Receives: Drug: Carfilzomib; Drug: Dexamethasone; Drug: cyclophosphamide
carfilzomib and dexamethasoneActive comparatorcarfilzomib at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) intravenously (iv) on days 1, 8, and 15, dexamethasone by mouth (po) at a dose of 20 mg (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16 , in 28 days cycles
Receives: Drug: Carfilzomib; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival (PFS)

    PFS is defined as the number of months from randomization to the disease progression or death due to any cause, whichever occurs first. The disease outcome determined will be the primary data source for the final PFS analysis.

    Measured: 36 months

Secondary outcomes (5)

  1. Safety of carfilzomib, dexamethasone and cyclophosphamide in number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    the safety as determined by the incidence of clinical and laboratory toxicities

    Measured: 2 years

  2. Efficacy of carfilzomib, dexamethasone and cyclophosphamide in number and rate of responses obtained

    Evaluate the efficacy of carfilzomib and dexamethasone in combination with cyclophosphamide in terms of rate of response in multiple myeloma (MM) patients.

    Measured: 2 years

  3. Time-to progression (TTP)

    Duration from randomization to disease progression, with deaths due to causes other than progression censored.

    Measured: 36 months

  4. Overall Survival (OS)

    Duration from the date of randomization until the date of death. The patients lost to follow-up will be censored at the date of the last visit.

    Measured: 36 months

  5. Efficacy of carfilzomib, dexamethasone and cyclophosphamide in rate of achievement of immunophenotypic CR

    Evaluate the efficacy of carfilzomib and dexamethasone in combination with cyclophosphamide in terms of achievement of immunophenotypic CR in multiple myeloma (MM) patients.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2017
  2. Study start18 Dec 2017
  3. Primary completionDec 2024 (estimated)
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
199 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03336073
Sponsor's protocol ID
GEM-KyCyDex
Status last verified
Sep 2022
First submitted
25 Oct 2017
Last updated
7 Sep 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • American Cancer Society. Cancer facts and figures 2005. Atlanta, GA: American Cancer Society 2005.

  • Arastu-Kapur S, Shenk K, Kirk CJ, et al. Nonproteasomal targets of proteasome inhibitors bortezomib and carfilzomib. Haematologica. 2009:94(s2). 14th Congress of the European Hematology Association 2009. Abstract 0939.

  • Berenson JR, Cartmell A, Bessudo A, Lyons RM, Harb W, Tzachanis D, Agajanian R, Boccia R, Coleman M, Moss RA, Rifkin RM, Patel P, Dixon S, Ou Y, Anderl J, Aggarwal S, Berdeja JG. CHAMPION-1: a phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma. Blood. 2016 Jun 30;127(26):3360-8. doi: 10.1182/blood-2015-11-683854. Epub 2016 May 12.

    PubMed 27207788

  • Boyle P, Ferlay J. Cancer incidence and mortality in Europe, 2004. Ann Oncol. 2005 Mar;16(3):481-8. doi: 10.1093/annonc/mdi098. Epub 2005 Feb 17.

    PubMed 15718248

  • Bringhen S, Petrucci MT, Larocca A, Conticello C, Rossi D, Magarotto V, Musto P, Boccadifuoco L, Offidani M, Omede P, Gentilini F, Ciccone G, Benevolo G, Genuardi M, Montefusco V, Oliva S, Caravita T, Tacchetti P, Boccadoro M, Sonneveld P, Palumbo A. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood. 2014 Jul 3;124(1):63-9. doi: 10.1182/blood-2014-03-563759. Epub 2014 May 22.

    PubMed 24855212

  • Demo SD, Kirk CJ, Aujay MA, Buchholz TJ, Dajee M, Ho MN, Jiang J, Laidig GJ, Lewis ER, Parlati F, Shenk KD, Smyth MS, Sun CM, Vallone MK, Woo TM, Molineaux CJ, Bennett MK. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007 Jul 1;67(13):6383-91. doi: 10.1158/0008-5472.CAN-06-4086.

    PubMed 17616698

  • de Waal EG, de Munck L, Hoogendoorn M, Woolthuis G, van der Velden A, Tromp Y, Vellenga E, Hovenga S. Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients. Br J Haematol. 2015 Dec;171(5):720-5. doi: 10.1111/bjh.13653. Epub 2015 Sep 11.

    PubMed 26358087

  • Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hajek R, Facon T, Ludwig H, Oriol A, Goldschmidt H, Rosinol L, Straub J, Suvorov A, Araujo C, Rimashevskaya E, Pika T, Gaidano G, Weisel K, Goranova-Marinova V, Schwarer A, Minuk L, Masszi T, Karamanesht I, Offidani M, Hungria V, Spencer A, Orlowski RZ, Gillenwater HH, Mohamed N, Feng S, Chng WJ; ENDEAVOR Investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016 Jan;17(1):27-38. doi: 10.1016/S1470-2045(15)00464-7. Epub 2015 Dec 5.

    PubMed 26671818

  • Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006 Sep;20(9):1467-73. doi: 10.1038/sj.leu.2404284. Epub 2006 Jul 20.

    PubMed 16855634

  • Fu W, Delasalle K, Wang J, Song S, Hou J, Alexanian R, Wang M. Bortezomib-cyclophosphamide-dexamethasone for relapsing multiple myeloma. Am J Clin Oncol. 2012 Dec;35(6):562-5. doi: 10.1097/COC.0b013e31822043f6.

    PubMed 21694573

  • Garcia-Sanz R, Gonzalez-Porras JR, Hernandez JM, Polo-Zarzuela M, Sureda A, Barrenetxea C, Palomera L, Lopez R, Grande-Garcia C, Alegre A, Vargas-Pabon M, Gutierrez ON, Rodriguez JA, San Miguel JF. The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma. Leukemia. 2004 Apr;18(4):856-63. doi: 10.1038/sj.leu.2403322.

    PubMed 14973508

  • Jawed I, Lee CM, Tward JD, et al. Survival outcomes for multiple myeloma over three decades: A Surveillance, Epidemiology, and End Results (SEER) analysis. J Clin Oncol. 2007;25(18_suppl). ASCO Annual Meeting 2007. Abstract 8019.

  • Kim YK, Sohn SK, Lee JH, Yang DH, Moon JH, Ahn JS, Kim HJ, Lee JJ; Korean Multiple Myeloma Working Party (KMMWP). Clinical efficacy of a bortezomib, cyclophosphamide, thalidomide, and dexamethasone (Vel-CTD) regimen in patients with relapsed or refractory multiple myeloma: a phase II study. Ann Hematol. 2010 May;89(5):475-82. doi: 10.1007/s00277-009-0856-x. Epub 2009 Nov 18.

    PubMed 19921192

  • Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90. doi: 10.1182/blood-2007-01-065888. Epub 2007 Jun 25.

    PubMed 17591945

  • Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. doi: 10.1182/blood-2011-11-395749. Epub 2012 Mar 15.

    PubMed 22422823

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carfilzomib, Dexamethasone and cyclophosphamide in people with Multiple Myeloma, run by PETHEMA Foundation at 24 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 7 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS) (time frame: 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03336073, which also lists 29 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2022.

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