A phase I study investigating the mean circulation time, biodistribution and safety of an infusion of cultured red cells (CRC) in patients with myelodysplastic syndrome (MDS) or patients in remission from haematologic malignancy
A phase I study investigating the mean circulation time, biodistribution and safety of an infusion of chromium isotope 51 labelled cultured red cells (CRC) in patients with MDS or patients in remission from haematologic malignancy.
Cell Therapies Pty Ltd
10 participants
May 3, 2018
Interventional
Conditions
Summary
This is a phase I study investigating the mean circulation time, biodistribution and safety of an infusion of cultured red cells (CRC) in patients with MDS or patients in remission from haematologic malignancies CRCs are enucleated red cells (reticulocytes) that are grown in culture from donor human haematopoietic stem cells. The collection, manufacturing and administration process used for CRC reduces the risks of infection and immune mediated transfusion reactions associated with traditional blood product administration. This trial will be conducted in patients with very low and low-risk MDS or previous haematologic malignancy in remission and not on active treatment and who are able to undergo infusion of CRC and who fulfil all of the other protocol-defined eligibility criteria. This is a single centre, Peter MacCallum Cancer Centre (PMCC) Study outline: The study will recruit four patients in the initial treatment phase. These patients will have a single infusion labelled cultured red cells at a dose of 0.7-1.5 x10^10 cells. They will be labelled with chromium and a cell surface marker called biotin. Following infusion the patients will undergo blood sampling, surface scanning, clinical review and physical examination at predefined intervals to determine mean circulation time of the red cells and evidence of distribution throughout the body. The Data Safety Monitoring Board will review the safety data, circulation times and biodistribution after the fourth patient’s day 27 post infusion assessment has been completed and make a recommendation on safety to proceed to expansion phase. The Principal Investigator and the Clinical Study Oversight Group will determine need to pursue the expansion phase in which up to six additional patients may be recruited. Patients in the expansion phase will be treated and evaluated in the same way as those in the initial phase. Up to 10 patients in total may be treated on this protocol. Mean CRC circulation time (mCCT) and biodistribution will be determined from data collected in the first 27 days post infusion using the 51Cr label. Patients will be monitored until 120 post infusion to monitor for mCCT, alloantibody development and delayed transfusion associated reactions. This Phase 1 study aims to determine the mean circulation time, biodistribution, safety and tolerability of CRCs in these patient groups. It is anticipated that the technology in this study will be used in the development of Red-Cell Therapeutics that will act as a protein/drug delivery mechanism in the treatment of a wide range of diseases.
Eligibility
Inclusion Criteria20
- Patients has either:
- o very-low or low-risk MDS as defined by the IPSS-R (Score 0-3); or
- o previous haematologic malignancy in remission.
- Patient has required at least one unit of packed red cells since the time of MDS or haematologic malignancy diagnosis.
- Patient is greater than or equal to 18 years of age
- Patient has provided written confirmation of informed consent on participant information and consent form
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Estimated life expectancy greater than or equal to 1 year.
- Adequate organ function as defined below:
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 1.5 x upper limit of normal (ULN); if liver function abnormalities are due to the underlying malignancy, then AST and ALT must be less than or equal to 2.5 x ULN;
- Total serum bilirubin less than or equal to ULN unless due to Gilbert’s Syndrome;
- Serum creatinine less than or equal to 1.25 x ULN; or if serum creatinine > 1.25 x ULN, then calculated (Cockcroft-Gault formula) glomerular filtration rate (GFR) greater than or equal to 60 mL/min;
- Haemoglobin (Hb) greater than or equal to 9.0 g/dL
- Absolute neutrophil count greater than or equal to 1,000/mm3 (not supported by growth factors in the preceding 1 month);
- Platelet count greater than or equal to 80,000/mm3 (without platelet transfusion or growth factor support in the preceding 1 month);
- Activated partial thromboplastin time (aPTT) less than or equal to 1.25 x ULN and international normalized ratio (INR) less than or equal to 1.3 (unless the subject is receiving therapeutic anticoagulants);
- Folate and Vitamin B12 levels WNL within 90 days prior to registration;
- Adequate iron status defined as serum ferritin greater than 20 ng/ml and transferrin saturation of greater than 30% within 90 days prior to registration;
- Haemolysis panel (serum bilirubin WNL; serum LDH less than or equal to the ULN; serum haptoglobin WNL; urine haemosiderin undetectable).
- Antibody screen negative on extended blood-typing panel.
Exclusion Criteria19
- Patients with intermediate to very-high risk MDS (IPSS-R score >3)
- Patients with active haematologic malignancy (excluding very-low or low risk MDS)
- Patients with symptomatic anaemia who require red blood cell transfusions of one or more units of packed cells more frequently than every two months.
- Patients who have received treatment with anti-cancer therapy (including but not be limited to chemotherapy, immunotherapy, biological therapy, targeted therapy or hormonal therapy within) within 3 months of registration.
- Concurrently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo.
- Concurrent medical conditions that in the judgment of the investigator will interfere with the objectives of the study or safety, including:
- History of haemolytic anaemia or autoimmune disorders that can affect red blood cell circulation times in the opinion of the investigator;
- Splenomegaly detectable by physical examination or radiographic assessment;
- Hepatomegaly detectable by physical examination or radiographic assessment;
- Clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease,
- Acute myocardial infarction, deep venous thrombosis or pulmonary embolism within 6 months of registration;
- Prior bone marrow or stem cell transplant;
- Previously known infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV).
- Any active infection requiring the use of parenteral anti-microbial agents or that is > Grade 2.
- Patient has not recovered from the adverse effects of previous treatments to pre-treatment baseline or Grade 1 by registration.
- Patients with known hypersensitivity to any component/excipient used in this study.
- Patients with previous transfusion reactions greater than Grade 1 reactions.
- Women of childbearing potential
- Patients whose primary language is other than English will be excluded from this study given 1) there is no clinical benefit for patients on this study and 2) the complexity of the information to be absorbed.
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Interventions
Patients will have a single infusion of Chromium isotope 51 (51Cr) labelled, biotinylated Cultured Red Cells at a dose of 0.7-1.5 x10^10 cells. The infusion will be administered over 15 minutes by nuclear medicine technicians. As this is a single infusion performed under observation to monitoring of adherence is required. The initial phase will include 4 patients. If there are no safety concerns then the sponsor may elect to proceed to the expansion phase with the inclusion of 6 additional patients. The dose of cells is the same in the initial and the expansion phase.
Locations(2)
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ACTRN12618000661279