Condition category
Cancer
Date applied
14/05/2015
Date assigned
14/05/2015
Last edited
16/08/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Mrs Helen Flight

ORCID ID

Contact details

University of Oxford
Department of Oncology
Oncology Clinical Trials Office (OCTO)
Old Road Campus Research Building
Roosevelt Drive
Oxford
OX3 7DQ
United Kingdom

Additional identifiers

EudraCT number

2015-000720-29

ClinicalTrials.gov number

Protocol/serial number

18953

Study information

Scientific title

A Phase I dose escalation trial of the humanized anti-CD47 monoclonal antibody Hu5F9-G4 in acute myeloid leukaemia

Acronym

CAMELLIA

Study hypothesis

The aim of this study is to determine whether a new drug, called Hu5F9-G4, is a safe and well tolerated treatment for patients with Acute Myeloid Leukaemia (AML), whose disease has either not responded to standard treatments or has relapsed following an initial response. There is an urgent need for new treatments for these patients, who currently only receive supportive care and have a median survival of only 2 months.

08/09/2015: Updated overall trial start date, and recruitment start date from 01/07/2015 to 15/10/2015. Changed recruitment end date to 15/04/2017 to 31/12/2017. Five additional funders added.

Ethics approval

South Central- Oxford C’, 14/05/2015, ref: 15/SC/0215

Study design

Non-randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Other

Trial type

Treatment

Patient information sheet

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

Condition

Topic: Cancer; Subtopic: Haematological Oncology; Disease: Leukaemia (acute myeloid)

Intervention

All patients will receive the trial drug Hu5F9-G4, there is no control arm. Hu5F9-G4 is given as an intravenous infusion once or twice a week. The trial is of a dose escalation design. Patients who respond to the first 4 weeks of treatment will have the option of continuing treatment for a further 8 weeks i.e. up to 12 weeks in total.

There is also allowance for patients to continue on treatment for a further 40 weeks (i.e. up to 1 year in total). (added 16/08/2016)

Intervention type

Biological/Vaccine

Phase

Drug names

Primary outcome measures

Maximum tolerated dosing regimen of Hu5F9-G4; Timepoint(s): Over 4 weeks of treatment

Secondary outcome measures

As of 16/08/2016:
1. CD47 receptor occupancy; Timepoint(s): Days 1, 8, 15, 22, 36, 53, 64, 81 and weeks 16, 28, 40, 52 and disease progression
2. Immunogenicity of Hu5F9-G4; Timepoint(s): Days 1, 29, 53 and 81, and weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
3. Impact of blood transfusion on Hu5F9-G4 pharmacokinetics; Timepoint(s): Days 1,4, 8, 15, 22, 25, 36, 50, 64, 78, and Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48 & 52
4. Pharmacokinetic profile of Hu5F9-G4; Timepoint(s): Days 1,4, 8, 15, 22, 25, 36, 50, 64, 78, and Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48 & 52
5. Preliminary evidence of anti-leukaemic activity of Hu5F9-G4; Timepoint(s): Days 25, 53, 81, and weeks 16, 28, 40 and 52
6. Safety of extending treatment duration to 1 year; Timepoint(s): Weeks 5- 52 of treatment

Initial:
1. CD47 receptor occupancy; Timepoint(s): Days 1, 8, 15, 22, 36, 53, 64, 81 and at disease progression
2. Immunogenicity of Hu5F9-G4; Timepoint(s): Days 1, 29, 53 & 81 (if positive repeat assay every 4 weeks until no longer positive)
3. Impact of blood transfusion on Hu5F9-G4 pharmacokinetics; Timepoint(s): Days 1, 4, 8, 15, 22, 25, 36, 50, 64 & 78
4. Pharmacokinetic profile of Hu5F9-G4; Timepoint(s): Days 1,4, 8, 15, 22, 25, 36, 50, 64 & 78
5. Preliminary evidence of anti-leukaemic activity of Hu5F9-G4; Timepoint(s): Days 25, 53 & 81 (per International Working Group AML response criteria (2003))
6. Safety of extending treatment duration to 12 weeks; Timepoint(s): Weeks 5-12 of treatment

Overall trial start date

15/10/2015

Overall trial end date

31/12/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Pathologically confirmed relapsed or refractory (primary refractory and relapsed refractory) AML (defined by WHO criteria) for which no further conventional therapy is suitable for the patient within 3 weeks of registration
2. Peripheral white blood cell (WBC) count =10x10*9/L within 1 week of registration (Day 7 to Day 1). Patients with WBC >10x10*9/L can be treated with hydroxycarbamide (up to 4 g/day) throughout the trial to reduce the WBC to =10x10*9/L prior to each dose of IMP. The white count must also be measured on the day of the first dose and be =10x10*9/L prior to each dose of IMP. The white count must also be measured on the day of the first dose and be =10x10*9/L
3. Male or female, Age >= 18 years
4. ECOG performance score of 01
5. Willing and able to comply with the protocol for the duration of the study, and scheduled followup visits and examinations
6. Willing to undergo blood transfusions as deemed clinically necessary
7. Pretreatment blood cross match completed
8. Written (signed and dated) informed consent and be capable of cooperating with protocol
9. Haematological and biochemical indices within the ranges shown below:
9.1. AST/SGOT or ALT/SGPT = 3 x ULN
9.2. Alkaline phosphatase = 2 x ULN
9.3. Bilirubin = 2x ULN (except for patients with a known or suspected history of Gilbert’s Syndrome)
9.4. eGFR >35 mls/min (Cockcroft and Galton method)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 30; UK Sample Size: 30

Participant exclusion criteria

1. Females: Pregnant or breastfeeding women, or women of childbearing potential unless effective method of contraception is used during and for 3 months after the trial. Males: unless an effective method of contraception is used during and for 3 months after the trial
2. Any prior exposure to Hu5F9G4 or other CD47 targeting agent
3. Treatment with any other investigational agent within 28 days prior to enrolment
4. Prior cytotoxic chemotherapy (with the exception of hydroxycarbamide), immunotherapy, or radiotherapy within 4 weeks prior to Day 1
5. Acute Promyelocytic Leukaemia
6. Patients with known inherited or acquired bleeding disorders
7. Previous allogeneic stem cell transplant
8. Evidence for active CNS involvement by leukaemia
9. Clinical evidence or known history of cardiopulmonary disease defined as follows:
9.1. Acute myocardial infarction within the last 12 months
9.2. Requirement for treatment of angina or existence of unstable angina
9.3. Congestive heart failure NYHA Class II–IV
9.4. Uncontrolled hypertension despite adequate treatment (sustained systolic BP > 150 or diastolic BP > 100)
10. Symptomatic intrinsic lung disease (chronic obstructive pulmonary disease, pulmonary fibrosis)
11. Other psychological, social or medical condition (e.g. active severe sepsis) physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results
12. Any other malignancy within the previous 24 months, with the exception of adequately treated cone biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin
13. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV

Recruitment start date

15/10/2015

Recruitment end date

15/04/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Churchill Hospital (lead site)
Oxford
OX3 7LJ
United Kingdom

Trial participating centre

St Bartholomew’s Hospital
London
E1 1BB
United Kingdom

Trial participating centre

Christie Hospital
Manchester
M20 4BX
United Kingdom

Trial participating centre

City Hospital
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Royal Liverpool Hospital
Liverpool
L7 8XP
United Kingdom

Trial participating centre

St James Hospital
Leeds
LS9 7TF
United Kingdom

Trial participating centre

University Hospital of Wales
Cardiff
CF14 4XW
United Kingdom

Sponsor information

Organisation

Forty Seven, Inc.

Sponsor details

1490 O’Brien Drive
Suite A
Menlo Park
CA
94304
United Kingdom

Sponsor type

Industry

Website

http://www.fortyseveninc.com/

Funders

Funder type

Charity

Funder name

Bloodwise

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

NIHR Oxford Biomedical Research Centre (BRC)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

CRUK Cancer Centre

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Virginia and D.K. Ludwig Fund for Cancer Research

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

California Institute for Regenerative Medicine

Alternative name(s)

CIRM

Funding Body Type

government organisation

Funding Body Subtype

federal/national government

Location

United States of America

Results and Publications

Publication and dissemination plan

Results of this trial will be submitted for publication in a peer‐reviewed journal. All presentations and publications will be pre‐agreed by the Combined Anti‐CD47 Clinical Trial Steering Committee (CTSC).

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

16/08/2016: Slight amendment made to intervention (date stamped in field), added amended secondary outcome measures. Changed sponsor contact details. Removed following exclusion criteria: Prior splenectomy. Removed Queen Elizabeth Hospital (London) from list of trial participating centres 23/06/2016: Changed sponsor from Stanford University to Forty seven Inc. Updated funder name from Leukaemia and Lymphoma Research to Bloodwise 29/02/2016: Cancer Help UK lay summary link added.