Topic: Cancer
Conditions
Interventions
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 r
Sponsors
Forty Seven, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 26/10/2017: 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; 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. 2. 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. 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. 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) Current inclusion criteria as of 02/08/2017: 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; 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. 2. 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. 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 meth
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 26/10/2017: 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 haematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease (GVHD), or requiring transplant-related immunosuppression 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 treatmen 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 Current exclusion criteria as of 02/08/2017: 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 haematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease (GVHD), or requiring transplant-related immunosuppression 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 Invest
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dosing regimen of Hu5F9-G4; Timepoint(s): Over 4 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Current as of 26/10/2017: 1. CD47 receptor occupancy; Timepoint(s): Days 1, 8, 11, 15, 18, 25, 36, 53, 64, 81 and weeks 16, 28, 40, 52 and every 12 weeks beyond week 52, 30-35 days post end of treatment, 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 every 4 weeks beyond week 52 and at 30-35 days post end of treatment. 3. Impact of blood transfusion on Hu5F9-G4 pharmacokinetics; Timepoint(s): Timings as per PK sampling. 4. Pharmacokinetic profile of Hu5F9-G4; Timepoint(s): Days 1,4, 8, 11, 15, 22, 25, 36, 50, 64, 78, and Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48 & 52 and every 4 weeks beyond week 52. 5. Preliminary evidence of anti-leukaemic/myelodysplastic activity of Hu5F9-G4; Timepoint(s): Days 25, 53, 81, and weeks 16, 28, 40 and 52 and every 12 weeks beyond week 52. 6. Safety of extending treatment duration: From week 5 until 30-35 day post end of treatment. As of 02/08/2017: 1. CD47 receptor occupancy; Timepoint(s): Days 1, 8, 11, 15, 18, 25, 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, 11, 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, 11, 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/myelodysplastic 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 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, 2 | — |
Countries
England, United Kingdom, Wales
Contacts
Public ContactTom Holmes
Outcome results
None listed