Study on the Safety and Efficacy of Cryopreserved Platelets in Hypoproliferative Thrombocytopenic Patients

NCT05067608 | Completed Phase 1 DMC

• 2 other identifiers: CPPL-DSO-20182018/2883
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to study the safety and efficacy of pooled buffy-coat derived platelets which had been frozen with dimethyl sulphoxide (DMSO), in the prevention of bleeding for patients with hypoproliferaitve thrombocytopenia. These platelets are hereafter referred to as cryopreserved platelets. Patients who have severely low platelet count due to impaired bone marrow function from chemotherapy or certain haematological conditions may need platelet transfusion to prevent spontaneous bleeding. Currently, platelets are stored in liquid form, and must be used within five to seven days of collection. In this study, DMSO is used to preserve platelets during freezing so that they can be stored for longer than five to seven days. Investigators hope to learn if thawed cryopreserved platelets are functional and safe for transfusion in humans.

Conditions

Hypoproliferative Thrombocytopenia

Keywords

Hypoproliferative thrombocytopenia; Cryopreserved; Transfusion; Platelets; Safety; Efficacy

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events related to platelet transfusion.

  There would be a close visual observation of the patient throughout the transfusion for the earliest signs of a transfusion reaction. Because patients can experience transfusion reactions several hours after the transfusion is completed, inpatients should be observed for late reactions during the subsequent 24 hour. Outpatient patients and their carer would be counselled about the possibility of the late adverse reactions and given access to immediate clinical help if they develop any symptoms of a transfusion reaction within 24 hour post-transfusion. Patients receiving cryopreserved platelets will be monitored and assessed for the side-effects of DMSO within 24 hour. These side effects include: headache, nausea, sedation, dizziness, abdominal or chest \& abdominal discomfort during and after transfusion. It also includes assessment for renal impairment related to DMSO by performing serum renal panel 18 to 30 hours post-transfusion of study platelets.

  Monitoring will be for 24 hours (serum test 18-30 hours) post-transfusion.

• Non-cutaneous Grade 2 or higher bleeding (as defined on the WHO bleeding scale)

  Patients will be monitored daily for bleeding during each thrombocytopenic period if they are inpatients. If they are outpatients, they will be reviewed for bleeding at each clinic visit, and they will be asked to keep a record of any bleeding symptoms which will also be reviewed at each clinical visit during each of the thrombocytopenic periods.

  Each thrombocytopenic period is up to 28 days from the first prophylactic platelet transfusion (shorter if platelet count recovers above target level before 28 days)

Secondary Outcomes (5)

• Platelet count increase (absolute increase and corrected count increment) post-platelet trantrsfusion

  Within approximately 24 hours prior, 1-4 hour and 18-30 hour post-transfusion.

• Changes in platelet activity (measured by viscoelastic hemostatic assay) post-platelet transfusion

  Within approximately 24 hours prior, 1-4 hour and 18-30 hour post-transfusion.

• Changes in procoagulant activity post-platelet transfusion

  Within approximately 24 hours prior and 1-4 hour post-transfusion.

• Incidence of all grades of bleeding (as defined on WHO bleeding scale)

  Each thrombocytopenic period is up to 28 days from the first prophylactic platelet transfusion of each arm (shorter if platelet count recovers above target level before 28 days)

• Total number and type of blood products transfused

  Each thrombocytopenic period is up to 28 days from the first prophylactic platelet transfusion of each arm (shorter if platelet count recovers above target level before 28 days)

Study Arms (2)

Control arm

ACTIVE COMPARATOR

Subjects in the "control" arm will receive normal pooled platelets for all of their transfusion within a single thrombocytopenic period. If subjects participate in the study for more than one thrombocytopenic period, they will automatically be enrolled in the opposing arm for their second thrombocytopenic period.

Biological: Control arm receiving normal (never before frozen) platelets as per current clinical practice

Treatment arm

EXPERIMENTAL

Subjects in the "treatment" arm will receive thawed cryopreserved pooled platelets for all of their transfusions (except for unplanned or urgent platelet transfusions outside stipulated periods when thawed cryopreserved platelets are unavailable) within a single thrombocytopenic period. If subjects participate in the study for more than one thrombocytopenic period, they will automatically be enrolled in the opposing arm for their second thrombocytopenic period.

Biological: Treatment arm receiving cryopreserved platelets

Interventions

Control arm receiving normal (never before frozen) platelets as per current clinical practice BIOLOGICAL

Liquid platelets arm (control) and may receive multiple platelet transfusions per thrombocytopenic cycle.

Control arm

Treatment arm receiving cryopreserved platelets BIOLOGICAL

Cryopreserved platelets arm (treatment) and may receive multiple platelet transfusions per thrombocytopenic cycle.

Treatment arm

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 21 years of age
• Be able to provide written informed consent
• Current or potential hypoproliferative thrombocytopenia with expected platelet count of \<20 X 109/L for a minimum of 5 days in a 28-day period
• If pre-menopausal female of child bearing potential, then the subject must have a negative serum pregnancy test prior to study commencement, and must be using an acceptable method of contraception during the study.
• Calculated creatinine clearance of \>30 ml/min (as calculated based on the Cockcroft-Gault equation; National Kidney Foundation 2017) at the point of recruitment, and within one week before transfusion

You may not qualify if:

• Pregnant
• Breastfeeding
• Current platelet refractoriness
• History of allergy or adverse reaction to DMSO
• History of veno-occlusive disease
• History of acute venous or arterial thromboembolism within the last 3 months.
• History of unprovoked venous thromboembolism
• On antiplatelets, NSAIDs or anticoagulants within 1 week, and TCM (traditional Chinese medicine) which are known to decrease platelet count or platelet function or increase bleeding tendency within 2 weeks of study enrolment.
• Received or will be receiving L-asparaginase chemotherapy within 7 days of platelet transfusion
• Renal impairment with calculated creatinine clearance of \<30ml/min.
• Non-cutaneous Grade 2 and above bleeding at the time of study assessment
• Presently with or a history of acute promyelocytic leukemia (APML), immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), haemolytic-uremic syndrome (HUS), or any thrombotic microangiopathy (TMA)
• Presently with or a history of heparin-induced thrombocytopenia
• Presently with disseminated intravascular coagulation (DIC) or other risk factor(s) for bleeding other than thrombocytopenia (including platelet dysfunction, PT ≥ 1.3 X upper limit of normal for the laboratory, PTT ≥ 1.3 X upper limit of normal for the laboratory, or fibrinogen ≤ 1 g/L)
• History of anaphylaxis from blood transfusion

Sponsors & Collaborators

• Singapore General Hospital: lead
• DSO National Laboratories: collaborator
• Health Sciences Authority, Singapore: collaborator

Study Sites (1)

Singapore General Hospital

Singapore, 169608, Singapore

Location

Related Publications (5)

• ClinicalTrials.gov: NCT02078284. Phase 1 safety study of dimethyl sulphoxide cryopreserved platelets.

  BACKGROUND

• Dumont LJ, Dumont DF, Unger ZM, Siegel A, Szczepiorkowski ZM, Corson JS, Jones MK, Christoffel T, Pellham E, Bailey SL, Slichter SJ; BEST Collaborative. A randomized controlled trial comparing autologous radiolabeled in vivo platelet (PLT) recoveries and survivals of 7-day-stored PLT-rich plasma and buffy coat PLTs from the same subjects. Transfusion. 2011 Jun;51(6):1241-8. doi: 10.1111/j.1537-2995.2010.03007.x. Epub 2011 Jan 7.

  PMID: 21214584 BACKGROUND

• Dumont LJ, Cancelas JA, Graminske S, Friedman KD, Vassallo RR, Whitley PH, Rugg N, Dumont DF, Herschel L, Siegal AH, Szczepiorkowski ZM, Fender L, Razatos A. In vitro and in vivo quality of leukoreduced apheresis platelets stored in a new platelet additive solution. Transfusion. 2013 May;53(5):972-80. doi: 10.1111/j.1537-2995.2012.03841.x. Epub 2012 Aug 6.

  PMID: 22882530 BACKGROUND

• Noorman F, van Dongen TT, Plat MJ, Badloe JF, Hess JR, Hoencamp R. Transfusion: -80 degrees C Frozen Blood Products Are Safe and Effective in Military Casualty Care. PLoS One. 2016 Dec 13;11(12):e0168401. doi: 10.1371/journal.pone.0168401. eCollection 2016.

  PMID: 27959967 BACKGROUND

• Slichter SJ, Jones M, Ransom J, Gettinger I, Jones MK, Christoffel T, Pellham E, Bailey SL, Corson J, Bolgiano D. Review of in vivo studies of dimethyl sulfoxide cryopreserved platelets. Transfus Med Rev. 2014 Oct;28(4):212-25. doi: 10.1016/j.tmrv.2014.09.001. Epub 2014 Sep 21.

  PMID: 25439164 BACKGROUND

MeSH Terms

Interventions

Platelet Count

Intervention Hierarchy (Ancestors)

Blood Cell Count; Cell Count; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Platelet Function Tests; Investigative Techniques; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Ang Ai Leen

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase 1b/2a single centre clinical trial. Eligible hypoproliferative thrombocytopenic adult patients enrolled in the study will be randomised into two arms. One arm is the "treatment" arm using cryopreserved platelets and the second is the "control" arm using liquid platelets. A recruitment period of two years is expected for 17 subjects in each arm. Subjects will automatically be crossed over to the other treatment arm once they have completed the first treatment arm and there is at least a 5-days interval without platelet transfusion. Subjects can be both inpatient and outpatient. During the thrombocytopenic period of 28 days, subjects may be required to have multiple platelet transfusions during this period.

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: October 5, 2021
• Study Start: October 25, 2019
• Primary Completion: March 24, 2021
• Study Completion: March 24, 2021
• Last Updated: October 5, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)