CAMELLIA: A Phase I dose escalation trial of the Humanized Anti-CD47 Monoclonal Antibody Hu5F9-G4 in Haematological Malignancies
Chief Investigator: Professor Paresh Vyas
Trial Sponsor: Forty Seven Inc.
Sponsor’s Representative in the EU: University of Oxford
EudraCT number: 2015-000720-29
Design: A multi-centre, non-randomized, Phase I, escalating dose titration cohort study of the CD47 blocking antibody Hu5F9-G4 in patients with relapsed or refractory acute myeloid leukaemia or Myelodysplastic Syndrome (MDS). The study has 2 parts: A dose titration schedule escalation phase (Part A) and a Maintenance phase (Part B).
Treatment: Hu5F9-G4; an anti-human CD47 monoclonal antibody will be administered intravenously 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 48 weeks in the first instance and may then be able to continue on treatment for longer (up to 52 weeks after the last patient is recruited), if treatment benefit is still being seen.
- Open to recruitment
- Recruitment start date: 16Nov2015
- Planned recruitment end date: Jan2018
- Recruiting sites:
- Churchill Hospital, Oxford
- The Christie, Manchester
- University Hospital Wales, Cardiff
- St James University Hospital, Leeds
- Royal Liverpool University Hospital
Main inclusion Criteria:
- 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; or confirmed myelodysplastic syndrome defined according to WHO classification, with an International Prognostic Scoring System (IPSS) risk category of intermediate-2 or high risk, that is relapsed, refractory or intolerant to conventional therapy within 3 weeks of registration.
- Peripheral white blood cell (WBC) count ≤20x109/L within 1 week of registration (Day -7 to Day 1). Patients with WBC >20x109/L can be treated with hydroxyurea (up to 4 g/day) throughout the trial to reduce the WBC to ≤20x109/L prior to each dose of IMP. The white count must also be measured on the day of the first dose and be ≤20x109/L. Oral etoposide (up to 200mg PO/ day) may be given as an alternative to hydroxyurea for patients who are intolerant to hydroxyurea or cannot achieve sufficient white count lowering on hydroxyurea.
- Male or female, Age >= 18 years
- ECOG performance score of 0-1
- Willing and able to comply with the protocol for the duration of the study, and scheduled follow-up visits and examinations
- Willing to undergo blood transfusions as deemed clinically necessary
- Pre-treatment blood cross match completed
- Written (signed and dated) informed consent and be capable of cooperating with protocol
- Biochemical indices within the ranges shown below:
- 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)
- eGFR >35 mls/min (Cockcroft and Galton method)
Main Exclusion Criteria:
- 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.
- Any prior exposure to Hu5F9-G4 or other CD47 targeting agents.
- Treatment with any other investigational agent within 28 days prior to enrolment.
- Prior cytotoxic chemotherapy (with the exception of hydroxycarbamide), immunotherapy, or radiotherapy within 4 weeks prior to Day 1.
- Acute Promyelocytic Leukaemia.
- Patients with known inherited or acquired bleeding disorders.
- Previous allogeneic haematopoietic stem cell transplant within 6 months prior to enrolment, active graft versus host disease (GVHD), or requiring transplant-related immunosuppression.
- Evidence for active CNS involvement by leukaemia.
- Clinical evidence or known history of cardiopulmonary disease defined as follows:
- Acute myocardial infarction within the last 12 months
- Requirement for treatment of angina or existence of unstable angina.
- Congestive heart failure NYHA Class II–IV
- Uncontrolled hypertension despite adequate treatment
- Symptomatic intrinsic lung disease (chronic obstructive pulmonary disease, pulmonary fibrosis).
- 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.
- Any other malignancy within the previous 24 months, with the exception of adequately treated conebiopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.
- Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
Primary outcome measure:
- Maximum tolerated dosing regimen of Hu5F9-G4;
Secondary outcome measures:
- CD47 receptor occupancy;
- Immunogenicity of Hu5F9-G4;
- Impact of blood transfusion on Hu5F9-G4 pharmacokinetics;
- Pharmacokinetic profile of Hu5F9-G4;
- Preliminary evidence of anti-leukaemic/myelodysplastic activity of Hu5F9-G4;
- Safety of extending treatment duration up to and beyond 1 year;
CAMELLIA Trial Office (OCTO):
UK Tel: 01865 227 198 or 01865 227 171