NCT02572492

Brief Summary

This study evaluates induction therapy with carfilzomib-cyclophosphamide-dexamethasone before salvage high-dose melphalan with autologous stem cell support (HDT) in multiple myeloma patients with relapse after HDT done at diagnosis. In addition, the study evaluates the effect of maintenance therapy after salvage HDT in multiple myeloma. After salvage HDT half of the patients receive maintenance therapy with carfilzomib/dexamethasone while the other half are observed without maintenance therapy.

Trial Health

50
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
200

participants targeted

Target at P75+ for phase_2 multiple-myeloma

Timeline
Completed

Started Jan 2015

Geographic Reach
5 countries

5 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2015

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

October 6, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 9, 2015

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 23, 2018

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2019

Completed
Last Updated

August 17, 2018

Status Verified

August 1, 2018

Enrollment Period

3.3 years

First QC Date

October 6, 2015

Last Update Submit

August 16, 2018

Conditions

Multiple Myeloma

Keywords

Multiple MyelomaRecurrenceCarfilzomibSalvage TherapyTransplantation, Autologous

Outcome Measures

Primary Outcomes (2)

  • Comparison of time to progression after high-dose melphalan with stem cell support (HDT) performed at diagnosis and time to progression after a salvage HDT combined with carfilzomib-cyclophosphamide-dexamethasone

    3 years

  • Comparison of time to progression between carfilzomib-dexamethasone maintenance and observation in patients treated with salvage HDT.

    3 years

Secondary Outcomes (6)

  • Adverse events assessed by CTCAE v4.0 in carfilzomib-cyclophosphamide-dexamethasone induction regime and carfilzomib as part of the high-dose melphalan conditioning

    5 months

  • Response rates of carfilzomib-cyclophosphamide-dexamethasone induction therapy and HDT

    5 months

  • Time to marrow regeneration (neutrophil- and platelet recovery) after the HDT

    3 weeks

  • Adverse events assessed by CTCAE v4.0 in maintenance treatment with carfilzomib-dexamethasone

    3 years

  • Comparison of overall survival between carfilzomib-dexamethasone maintenance and observation in patients treated with a salvage HDT

    3 years

  • +1 more secondary outcomes

Study Arms (2)

Carfilzomib/dexamethasone maintenance

EXPERIMENTAL

Carfilzomib/dexamethasone maintenance after salvage HDT

Drug: Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalanDrug: Carfilzomib/dexamethasone maintenance

Observation without maintenance

SHAM COMPARATOR

Observation without maintenance after salvage HDT

Drug: Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalanDrug: Observation without carfilzomib/dexamethasone maintenance

Interventions

Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalanDRUG

All patients entering the study receive four series of CAR-CY-DEX (Cycle 1 with iv carfilzomib 20 mg/sqm on days 1 and 2, and iv carfilzomib 36 mg/sqm on days 8, 9, 15 and 16. Cycle 2 - 4 with iv carfilzomib 36 mg/sqm on days 1, 2, 8, 9, 15 and 16. P.o. cyclophosphamide 300 mg/sqm on days 1, 8 and 15 and p.o. dexamethasone 20 mg on days 1, 2, 8, 9, 15 and 16 in each 28-days series) Subsequently all patients receive the conditioning regimen: Iv carfilzomib 27 mg/sqm on day -2 and -1 Iv melphalan 200 mg/sqm on day -2 \> 2.0 m CD34+ stem cells/kg body weight on day 0

Also known as: Kyprolis
Carfilzomib/dexamethasone maintenanceObservation without maintenance
Carfilzomib/dexamethasone maintenanceDRUG

Maintenance therapy two months after salvage HDT with iv carfilzomib 27 mg/sqm every second week and p.o. dexamethasone 20 mg every second week. The maintenance dose of carfilzomib will be escalated to 56 mg/sqm after 4 weeks provided acceptable side effects.

Also known as: Kyprolis
Carfilzomib/dexamethasone maintenance
Observation without carfilzomib/dexamethasone maintenanceDRUG

Observation without carfilzomib/dexamethasone maintenance

Observation without maintenance

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Myeloma diagnosis according to IMWG criteria
  • First treatment demanding relapse after HDT according to IMWG criteria
  • More than 2.0 x 10m CD34+ stem cells / kg body weight in the freezer for stem cell support
  • Signed informed consent given prior to any study related activities have been performed
  • Age \> 18 years

You may not qualify if:

  • Demographic
  • Allogeneic transplantation scheduled as a part of the treatment
  • Treatment demanding relapse less than one year after HDT
  • Myeloma treatment after the first HDT, except radiotherapy, bisphosphonates, denosumab and corticosteroids less than 6 days for symptom control
  • Patients not having received HDT as first line treatment
  • Previous treatment with carfilzomib
  • Expected survival of less than six months
  • Performance status (WHO) ≥ 3
  • Laboratory
  • Serum M-component \< 5 g/l and urine M-component \< 200 mg/l
  • Any of the following laboratory abnormalities:
  • Absolute neutrophil count (ANC) \< 1.0 × 109/L
  • Hemoglobin \< 5 mmol/L (\<80 g/L) (prior RBC transfusion or recombinant human erythropoietin use is permitted)
  • Platelet count \< 50 × 109/L (\< 30 × 109/L if myeloma involvement in the bone marrow is \> 50%)
  • Serum ALT or AST \> 3.5 times the upper limit of normal and serum direct bilirubin \> 34 µmol/L (2 mg/dL)
  • +17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Turku University Hospital

Turku, 20520, Finland

Location

Vilnius University hospital "Santariskiu Clinics"

Vilnius, Lithuania

Location

Oslo University Hospital

Oslo, 4950, Norway

Location

Skåne University Hospital

Lund, SE-221 85, Sweden

Location

MeSH Terms

Conditions

Multiple MyelomaRecurrence

Interventions

Neoadjuvant TherapycarfilzomibObservation

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Combined Modality TherapyTherapeuticsMethodsInvestigative Techniques

Study Officials

  • Henrik Gregersen, MD

    Aalborg University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Consultant

Study Record Dates

First Submitted

October 6, 2015

First Posted

October 9, 2015

Study Start

January 1, 2015

Primary Completion

April 23, 2018

Study Completion

April 1, 2019

Last Updated

August 17, 2018

Record last verified: 2018-08

Locations

NO(1)FI(1)SE(1)DK(1)LI(1)