Condition category
Cancer
Date applied
29/07/2011
Date assigned
21/09/2011
Last edited
21/09/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Peter Hillmen

ORCID ID

Contact details

Department of Haematology
Bexley Wing
St. James’'s University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
+44 (0)113 206 8513
peter.hillmen@nhs.net

Additional identifiers

EudraCT number

2011-000796-14

ClinicalTrials.gov number

Protocol/serial number

HM10/9652

Study information

Scientific title

Combination fludarabine and cyclophosphamide (FC) plus Ofatumumab at Standard or Mega dose In Chronic lymphoid leukemia (CLL): a phase II, multi-centre, randomised, open, parallel group trial

Acronym

COSMIC

Study hypothesis

This trial will assess the efficacy of standard dose and high (mega) dose of ofatumumab in combination with chemotherapy (fludarabine and cyclophosphamide) in relapsed B-CLL patients.

Ethics approval

Submitted to NRES Committee Yorkshire and The Humber –Leeds East - approval pending

Study design

Phase II multi-centre randomised open parallel group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Chronic Lymphocytic Leukaemia (CLL)

Intervention

1. Fludarabine, cyclophosphamide and standard dose ffatumumab (Standard Of-FC):
1.1. Fludarabine (oral*) - 24mg/m2/day - Day 1 to 5 (Cycle 1 to 6)
1.2. Cyclophosphamide (oral*) - 150mg/m2/day - Day 1 to 5 (Cycle 1 to 6)
1.3. Ofatumumab [intravenous (IV)] - 300mg - Day 1 and 1000mg Day 8 (Cycle 1 only)
1.4. Ofatumumab (IV) - 1000mg - Day 1 (Cycle 2 to 6)

2. Fludarabine, cyclophosphamide and high dose ofatumumab (Mega-Of-FC):
2.1. Fludarabine (oral*) - 24mg/m2/day - Day 1 to 5 (Cycle 1 to 6)
2.2. Cyclophosphamide (oral*) - 150mg/m2/day - Day 1 to 5 (Cycle 1 to 6)
2.3. Ofatumumab (IV) - 300mg - Day 1 (Cycle 1) followed by 2000mg weekly for 8 doses, followed by 2000mg monthly for 3 doses

Intervention type

Drug

Phase

Phase II

Drug names

Fludarabine, cyclophosphamide, ofatumumab

Primary outcome measures

Proportion of patients achieving a Complete Response (CR or CR(i)), as defined by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria. Measured 3 months after the therapy.

Secondary outcome measures

1. Proportion of patients with undetectable minimal residual disease (MRD)
2. Overall response rate defined as complete or partial remission by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
3. Progression-free survival at 2 years
4. Overall survival at 2 years
5. Time to MRD relapse in MRD negative patients
6. Safety and toxicity

Overall trial start date

01/01/2012

Overall trial end date

01/07/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. At least 18 years old
2. Chronic lymphocytic leukaemia requiring therapy
3. Previous treatment with at least one chemotherapeutic regime
4. Be capable of giving written informed consent
5. World Health Organisation (WHO) performance status (PS) of 0, 1, or 2
6. Life expectancy of at least 12 weeks
7. Considered fit enough to receive fludarabine-based combinations

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

82

Participant exclusion criteria

1. Fludarabine refractory: defined as no response to or relapse within 6 months of fludarabine alone or in combination with cyclophosphamide (FC)
2. Relapse within 12 months of FC with rituximab (FCR)
3. Deletion of chromosome 17p on fluorescent in-situ hybridisation (FISH) [will be performed in Haematological Malignancy Diagnostic Service (HMDS) at screening]
4. Previous treatment with ofatumumab either alone or in combination with chemotherapy
5. Toxicity attributable to purine analogues such as autoimmune haemolytic anaemia,
neurological toxicity or allergy
6. Active infection
7. Other severe, concurrent (particularly cardiac or pulmonary) diseases or mental disorders that could interfere with their ability to participate in the study
8. Patients with a creatinine clearance of less than 30ml/min (either measured or derived by the Cockcroft-Gault formula)
9. Pregnant, lactating or women of child bearing potential unwilling to use medically approved contraception whilst receiving treatment and for 12 months after treatment has finished
10. Men whose partners are capable of having children but who are not willing to use
appropriate medically approved contraception whilst receiving treatment and for 12 months after treatment has finished, unless they are surgically sterile
11. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per Investigator assessment)
12. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrolment, whichever is longer, or currently participating in any other interventional clinical study
13. Other past or current malignancy. Subjects who have been free of malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.
14. Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy
15. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C
16. History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
17. Known human immunodeficiency (HIV) positive
18. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomisation, congestive heart failure New York Heart Association (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
19. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the Investigator may represent a risk for the patient.
20. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded
21. Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result
screening laboratory values:
21.1. Platelets <50 x 109/L (unless due to involvement by CLL)
21.2. Neutrophils <1.0 x 109/L (unless due to involvement by CLL)
21.3. Creatinine clearance below 30ml/min (between 30 and 60ml/min the fludarabine dose will be reduced)
21.4. Total bilirubin >1.5 times upper normal limit (unless due to CLL involvement of liver or a known history of Gilbert’s disease)
21.5. Alanine aminotransferase (ALT) >2.5 times upper normal limit (unless due to CLL involvement of liver)
21.6. Alkaline phosphatase >2.5 times upper normal limit (unless due to disease involvement of the liver or bone marrow by CLL)

Recruitment start date

01/01/2012

Recruitment end date

01/07/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

St. James’'s University Hospital
Leeds
LS9 7TF
United Kingdom

Sponsor information

Organisation

Leeds Teaching Hospitals NHS Trust (UK)

Sponsor details

Research and Development
34 Hyde Terrace
Leeds
LS9 6LN
United Kingdom
+44 (0)113 392 2878
derek.norfolk@leedsth.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

GlaxoSmithKline

Alternative name(s)

GlaxoSmithKline Plc., GSK

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

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

2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/27645620

Publication citations

Additional files

Editorial Notes

21/09/2016: Publication reference added.