Condition category
Cancer
Date applied
02/12/2010
Date assigned
12/05/2011
Last edited
26/11/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Faith Davies

ORCID ID

Contact details

Haemato-Oncolocy Unit
Royal Marsden NHS Foundation Trust
Downs Road
Sutton
SM2 5PT
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HM10 9644

Study information

Scientific title

An open label, multicentre, phase I/II dose escalation trial of carfilzomib in combination with doxorubicin and dexamethasone (CAD) therapy in transplant eligible relapsed myeloma patients

Acronym

MUK 02

Study hypothesis

During the dose finding phase, the primary objective of this trial is to determine the maximum tolerated dose (MTD) of carfilzomib in combination with doxorubicin and dexamethasone (CAD). In the dose expansion phase the primary objective will be to estimate the response rate to four cycles of CAD therapy at MTD identified in the dose finding stage in transplant eligible relapsed myeloma patients.

Within the extension phase there are also the following secondary objectives:
1. Assess the safety and toxicity of CAD therapy
2. Assess the feasibility to mobilise stem cells following CAD therapy
3. Estimate maximum response to therapy
4. Estimate time to maximum response to therapy
5. Estimate progression free survival following CAD therapy
6. Assess the feasibility of delivering CD maintenance

Ethics approval

Not provided at time of registration

Study design

Open label multicentre phase I/II dose escalation trial

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Multiple myeloma

Intervention

Dose escalation:

Dose level 1
Carfilzomib 20mg/m2 on days 1 and 2 of cycle 1 only, 27mg/m2 on days 8-9 and 15-16 of cycle 1 and all subsequent doses. Adriamycin® (doxorubicin) 9.0 mg/m2 days 1, 2, 15 and 16. dexamethasone 40mg days 1, 2, 8, 9, 15 and 16

Dose level 2
Carfilzomib 20mg/m2 on days 1 and 2 of cycle 1 only, 36mg/m2 on days 8-9 and 15-16 of cycle and all subsequent doses. Adriamycin® (doxorubicin) 9.0 mg/m2 days 1, 2, 15 and 16. dexamethasone 40mg days 1, 2, 8, 9, 15 and 16

Dose level 3
Carfilzomib 20mg/m2 on days 1 and 2 of cycle 1 only, 45mg/m2 on days 8-9 and 15-16 of cycle 1 and all subsequent doses. Adriamycin® (doxorubicin) 9.0 mg/m2 days 1, 2, 15 and 16. dexamethasone 40mg days 1, 2, 8, 9, 15 and 16

Patients will receive four cycles of CAD and will be given the option of a further four cycles of consolidation therapy. Patients will then receive carfilzomib and dexamethasone maintenance therapy until disease progression and will be followed up every 2 months.

26/11/2012: Please note that this trial was never started.

Intervention type

Drug

Phase

Phase I/II

Drug names

Carfilzomib, doxorubicin, dexamethasone

Primary outcome measures

The primary endpoints for the dose escalation phase is dose limiting toxicities within the first cycle of treatment (28 days). In the dose expansion phase, the primary endpoint will be the proportion of patients achieving at least a partial response after four cycles of CAD.

Secondary outcome measures

1. The proportion of patients for whom stem cell cell mobilisation is possible following CAD therapy
2. Safety and toxicity
3. Maximum response rate within four cycles of CAD
4. Maximum response rate within four cycles of CAD, consolidation therapy and maintenance therapy (i.e. maximum response to therapy)
5. Time to maximum response to therapy (i.e. within four cycles of CAD, consolidation therapy and maintenance therapy)
6. Progression-free survival
7. Feasibility of CD-maintenance therapy

Overall trial start date

01/04/2011

Overall trial end date

01/04/2016

Reason abandoned

Lack of funding/sponsorship

Eligibility

Participant inclusion criteria

1. Able to give informed consent and willing to follow study protocol
2. Aged over 18 years, either sex
3. Patients with relapsed myeloma requiring therapy
4. Transplant eligible
5. Adequate renal function (creatinine clearance greater than or equal to 30 ml/min) within 14 days prior to study entry
6. Adequate liver function (alanine aminotransferase [ALT]/aspartate aminotransferase [AST] less than 3 x upper limit of normal [ULN]) within 14 days prior to study entry
7. Adequate bone marrow reserve (haemoglobin [Hb] greater than 8.0 g/dL, absolute neutrophil count [ANC] greater than 1.0 x 10^9/L, platelets [Plts] greater than 75 x 10^9/L) within 14 days prior to study entry
8. Female subjects of child-bearing potential must have a negative pregnancy test within 24 hours prior to starting therapy and agree to use dual methods of contraception for the duration of the study. Male subjects must agree to use a barrier method of contraception for the duration of the study if sexually active with a female of child-bearing potential.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

48

Participant exclusion criteria

1. Unable to tolerate an aggressive fluid hydration regimen (e.g. due to pre-existing pulmonary, cardiac or renal impairment)
2. Received an investigational medicinal product at any dose within 28 days of study entry (registration)
3. Concurrent or previous malignancies (less than 12 months post end of treatment) at other sites, with the exception of appropriately treated localised epithelial skin or cervical cancer. Patients with histories (greater than or equal to 12 months) of other tumours may be entered.
4. Seropositive for human immunodeficiency [HIV], or active hepatitis A, B or C infection
5. Any history of hypersensitivity to any of the study medications or excipients
6. Patients with active uncontrolled infections
7. Patients with peripheral neuropathy Common Toxicity Criteria (CTC) grade 3 or higher within 14 days prior to study entry
8. Poorly controlled or serious medical or psychiatric illness that, in the Investigator's opinion, is likely to interfere with participation and/or compliance in this clinical study
9. Pregnant or breast feeding

Recruitment start date

01/04/2011

Recruitment end date

01/04/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Haemato-Oncolocy Unit
Sutton
SM2 5PT
United Kingdom

Sponsor information

Organisation

University of Leeds (UK)

Sponsor details

Clarendon Way
Leeds
LS2 9JT
United Kingdom

Sponsor type

University/education

Website

http://www.leeds.ac.uk/

Funders

Funder type

Charity

Funder name

Myeloma UK (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes