Tranexamic Acid for Blood Cancer Patients Undergoing Stem Cell Transplant
(PATH Trial)
Recruiting in Palo Alto (17 mi)
+10 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Ottawa Hospital Research Institute
Must not be taking: Anticoagulants, Antiplatelets
Disqualifiers: Thrombotic events, Angina, Renal impairment, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 5 Jurisdictions
Trial Summary
What is the purpose of this trial?It is hypothesized that a strategy using prophylactic oral and intravenous Tranexamic Acid (TXA) with therapeutic platelet transfusions (if required) is safe and more effective than prophylactic platelet transfusions in patients undergoing an autologous hematopoietic stem cell transplantation (ASCT).
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot participate if you require anticoagulant or anti-platelet drugs during the stem cell transplant.
What data supports the effectiveness of the drug Tranexamic Acid for blood cancer patients undergoing stem cell transplant?
Tranexamic Acid (TXA) is known to reduce blood loss and the need for blood transfusions in various surgeries, including hip, knee, and shoulder replacements, as well as in cancer patients undergoing bone tumor surgeries. This suggests it may help manage bleeding in blood cancer patients undergoing stem cell transplants.
12345Is Tranexamic Acid (TXA) safe for use in humans?
Tranexamic Acid (TXA) has been used safely in humans for various conditions, including reducing bleeding during surgeries. It is generally well-tolerated, but like any medication, it can have side effects, which are usually mild and may include nausea or diarrhea.
678910How is the drug Tranexamic Acid unique for blood cancer patients undergoing stem cell transplant?
Tranexamic Acid (TXA) is unique because it helps reduce blood loss by preventing the breakdown of blood clots, which is particularly beneficial for patients undergoing procedures like stem cell transplants where blood conservation is crucial. Unlike other treatments, TXA is an antifibrinolytic (prevents clot breakdown) and is used in various bleeding conditions, making it a versatile option for managing blood loss.
13111213Eligibility Criteria
This trial is for adults over 18 with blood cancers undergoing autologous stem cell transplantation. They must consent to the treatment plan and not need anticoagulant drugs during the procedure. People with color vision disturbances, recent thrombosis, urinary bleeding, allergies to Tranexamic Acid, active angina, platelet transfusion issues due to HLA antibodies, significant past bleeding events or renal impairment can't participate.Inclusion Criteria
Patients providing written informed consent prior to starting transplantation
I am 18 or older and having a stem cell transplant for blood cancer.
Exclusion Criteria
I had a serious bleeding event in the last year.
My kidney function is significantly impaired.
I have a genetic blood clotting or bleeding disorder.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either prophylactic Tranexamic Acid or prophylactic platelet transfusions during the post-transplant period
4 weeks
Daily monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment, including quality of life and adverse reactions
6 months
Weekly assessments up to 30 days, then periodic assessments up to 180 days
Long-term Follow-up
Economic analyses and long-term outcomes are assessed
5 years
Participant Groups
The PATH III Trial is testing if using prophylactic oral and intravenous Tranexamic Acid (TXA) combined with therapeutic platelet transfusions when needed is safer and more effective than just regular preventive platelet transfusions in patients having a stem cell transplant for treating blood cancers.
2Treatment groups
Experimental Treatment
Active Control
Group I: Prophylactic Tranexamic AcidExperimental Treatment1 Intervention
Patients allocated to the prophylactic Tranexamic Acid group will receive a standardized routine oral or intravenous dose of Tranexamic Acid 1 gram three times daily.
Group II: Prophylactic Platelet TransfusionActive Control1 Intervention
Patients allocated to the prophylactic platelet transfusion group will receive a platelet transfusion when the measured platelet count is less than 10 x 109/L.
Tranexamic Acid is already approved in United States, European Union, Canada, Japan, Australia for the following indications:
🇺🇸 Approved in United States as Tranexamic Acid for:
- Heavy menstrual bleeding
- Prevention of excessive bleeding during surgeries
🇪🇺 Approved in European Union as Tranexamic Acid for:
- Heavy menstrual bleeding
- Prevention of excessive bleeding during surgeries
- Hereditary angioedema
🇨🇦 Approved in Canada as Tranexamic Acid for:
- Heavy menstrual bleeding
- Prevention of excessive bleeding during surgeries
🇯🇵 Approved in Japan as Tranexamic Acid for:
- Heavy menstrual bleeding
- Prevention of excessive bleeding during surgeries
🇦🇺 Approved in Australia as Tranexamic Acid for:
- Heavy menstrual bleeding
- Prevention of excessive bleeding during surgeries
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial UniversitySt. John's, Canada
University of ManitobaWinnipeg, Canada
Tom Baker Cancer CentreCalgary, Canada
Cross Cancer InstituteEdmonton, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Ottawa Hospital Research InstituteLead Sponsor
Alberta Cancer FoundationCollaborator
References
Tranexamic acid in patients with current or former cancer undergoing hip and knee arthroplasty. [2021]While tranexamic acid (TXA) is an excellent mechanism to reduce blood loss in arthroplasty, its safety in cancer patients-who could potentially benefit the most from blood conservation-is unknown.
Tranexamic acid reduces blood loss after primary shoulder arthroplasty: a double-blind, placebo-controlled, prospective, randomized controlled trial. [2022]Tranexamic acid (TXA) is an antifibrinolytic that has been shown to decrease blood loss and transfusion rates after hip and knee arthroplasty, with only limited evidence to support its use in shoulder arthroplasty. This study was conducted to determine whether intravenous (IV) TXA is more effective than placebo in reducing blood loss after primary total shoulder arthroplasty (TSA).
[Tranexamic acid reduces haematomas but not pain after total knee arthroplasty]. [2013]Tranexamic acid (TxA) reduces total blood losses (TBL) and allogenic transfusion (TH) after total knee arthroplasty (TKA). TBL can be external (surgical field, drains), or hidden (haematomas). Haematomas induce pain and limit postoperative rehabilitation. The aim of the study was to evaluate if TxA reduces haematomas and pain after TKA.
Platelet transfusion and tranexamic acid to prevent bleeding in outpatients with a hematological disease: A Dutch nationwide survey. [2021]There is scarce evidence about the effectiveness of anti-bleeding measures in hematological outpatients experiencing persistent severe thrombocytopenia. We aim to describe clinical practice and clinicians' considerations on the administration of prophylactic platelet transfusions and tranexamic acid (TXA) to outpatients with acute leukemia, myelodysplastic syndrome (MDS), or aplastic anemia (AA) in the Netherlands.
Tranexamic acid improves early postoperative mobilization in cancer patients undergoing endoprosthetic reconstruction. [2022]Tranexamic acid (TXA) has been shown to decrease perioperative blood loss, transfusions, and cost in patients undergoing resection of aggressive bone tumors and endoprosthetic reconstruction. This study explored the effect of TXA administration on postoperative mobilization in these patients.
Optimal conditioning regimen for haplo-identical stem cell transplantation in adult patients with acquired severe aplastic anemia: Prospective de-escalation study of TBI and ATG dose. [2019]This prospective study explored an optimal conditioning regimen to ensure engraftment with minimal toxicity in adult patients with severe aplastic anemia (SAA) who received haplo-identical stem cell transplantation from a related mismatched donor (Haplo-SCT). We explored a safe and sufficient dose of rabbit ATG (Thymoglobulin) in combination with 800 cGy total body irradiation (TBI) and fludarabine (Flu, 30 mg/m2 /day) for 5 days using step-by-step dose de-escalation. The dose of ATG was de-escalated from 10 mg/kg (group 1), to 7.5 mg/kg (group 2), to 5 mg/kg (group 3), and the TBI dose was reduced to 600 cGy (group 4) beginning in October 2014. If one patient developed transplant-related mortality (TRM) with engraftment in a group, we moved to the next lower dose group. Thirty-four patients were enrolled in groups 1-3 (n = 10) and 4 (n = 24). All patients achieved primary engraftment. The incidence of acute GVHD (grade ≥ 2) and chronic GVHD (≥ moderate) was 29.4% and 14.7%, respectively. With a median follow-up of 56.6 and 21.8 months in groups 1-3 and group 4, respectively, the 2-year probability of overall survival (91.7% in group 4 vs 70% in groups 1-3, P = 0.155) and GVHD-free survival (78.4% in group 4 vs 50% in groups 1-3, P = 0.115) was shown tended to be better in group 4. This study explored an optimal conditioning with step-by-step de-escalation dosage of ATG and TBI to reduce TRM with sustained graft function. TBI-600 cGy/Flu/intermediate-dose ATG resulted in feasible outcomes of Haplo-SCT for adult patients with SAA.
Phase I study of high-dose thiotepa with busulfan, etoposide, and autologous stem cell support in children with disseminated solid tumors. [2019]The aim of this phase I study was to define the maximum tolerated dose (MTD) of thiotepa (TT), administered with busulfan (BU) 480 mg/m(2) and etoposide 2,400 mg/m(2), followed by autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (APBSCT) support in children with solid tumors either disseminated at diagnosis or after relapse.
Phase I and pharmacokinetic evaluation of thiotepa in the cerebrospinal fluid and plasma of pediatric patients: evidence for dose-dependent plasma clearance of thiotepa. [2023]A Phase I trial of thiotepa (TT) administered as an i.v. bolus was performed in 19 children with refractory malignancies. The starting dose was 25 mg/m2 with escalations to 50, 65, and 75 mg/m2. Seven additional patients were treated with 8-h infusions at 50 or 65 mg/m2. The maximum tolerated bolus dose was 65 mg/m2. Reversible myelosuppression was the dose-limiting toxicity. The plasma and cerebrospinal fluid (CSF) pharmacokinetic parameters of TT and its major active metabolite tepa (TP) were also evaluated. When the bolus or infusion methods of TT administration were compared, there was little difference observed in any pharmacokinetic parameter for either TT or TP. The plasma disappearance of TT was rapid and biphasic with half-lives of 0.14 to 0.32 and 1.34 to 2.0 h. Dose-dependent pharmacokinetics was demonstrated by steadily declining plasma clearance with increasing TT dose. Clearance values declined from 28.6 liters/m2/h at the 25-mg/m2 dose to 11.9 liters/m2/h at the 75-mg/m2 dose. The half-life of TP was longer than that of TT and ranged between 4.3 and 5.6 h. There was evidence of the saturation of TP production. TT and TP both exhibited excellent penetration into the CSF, producing lumbar and ventricular concentrations which were nearly identical to simultaneous plasma concentrations. In one patient with a Rickham reservoir, the CSF:plasma area under the (concentration x time) curve ratios for TT and TP were 1.01 and 0.95, respectively. The above data indicate that TT can be safely administered to pediatric patients at doses higher than conventionally used. The favorable CSF penetration of TT and TP suggests that Phase II studies of TT be considered in patients with central nervous system tumors.
Early outcomes after allogeneic hematopoietic SCT in pediatric patients with hematologic malignancies following single fraction TBI. [2021]Fractionated TBI (FTBI) followed by allogeneic hematopoietic SCT results in donor engraftment and improves survival in children with high-risk hematologic malignancies. However, acute toxicities (skin, lung and mucosa) are common after FTBI. Late complications include cataracts, endocrine dysfunction, sterility and impaired neurodevelopment. Instead of FTBI, we used low-dose single fraction TBI (550 cGy) with CY as transplant conditioning for pediatric hematologic malignancies. GVHD prophylaxis included CYA and short-course MTX; methylprednisolone was added for unrelated donor transplants. A total of 55 children in first (40%) or second remission and beyond (60%) underwent transplantation from BM (65%) or peripheral blood; 62% from unrelated donors; 22% were mismatched. Median follow-up was 18.5 months (1-68). Overall survival and disease-free survival at 1 year were 60 and 47%, respectively. Acute toxicities included grade 3-4 mucositis (18%), invasive infections (11%), multiorgan failure/shock (11%), hemolytic anemia (7%), veno-occlusive disease (4%) and renal failure (4%). TRM was 11% at 100 days. Non-relapse mortality was 6% thereafter. Graft rejection occurred in 2%. Three patients (5%) died of GVHD. The regimen was well tolerated even in heavily pretreated children and supported donor cell engraftment; long-term follow up is in progress.
[Efficacy and safety of weekly taxol (TXL) for advanced recurrent breast cancer evaluated in a multi-center cooperative clinical trial]. [2015]A multi-center cooperative clinical trial was undertaken to evaluate the safety and efficacy of weekly taxol (TXL) therapy combined with short-premedication as a pretreatment in an effort to determine if TXL can be used in ambulatory treatment. TXL was administered at 60 mg/m2 to patients with advanced recurrent breast cancer once a week without a rest or with a rest for 1 week after treatment for 3 weeks. A total of 36 patients were finally enrolled. The site of recurrence was the local region in 8 patients, lung/pleura in 24, liver in 9, bone in 16, lymph nodes in 15, epicardium in 2, and brain metastasis in 2. The response was CR in 2, PR in 12, NC in 9, PD in 8, and NE in 5, with a response rate of 45.2%. Grade 4 anorexia was reported as non-hematotoxicity. All other adverse reactions, such as myalgia/arthralgia and peripheral neuropathy, were mild (grade 1 or 2). Hematotoxic effects observed in this study included only grade 3 leukopenia in 5 patients, neutropenia in 4, and decreases in hemoglobin in 1.
The impact of prehospital TXA on mortality among bleeding trauma patients: A systematic review and meta-analysis. [2023]Tranexamic acid (TXA) is an antifibrinolytic drug associated with improved survival among trauma patients with hemorrhage. Tranexamic acid is considered a primary hemostatic intervention in prehospital for treatment of bleeding alongside blood product transfusion.
Topical Tranexamic Acid for Hemostasis of an Oral Bleed in a Patient on a Direct Oral Anticoagulant. [2022]Tranexamic acid (TXA) is an antifibrinolytic agent currently approved and utilized in the treatment of dysfunctional uterine bleeding, traumatic extracranial hemorrhage, anterior epistaxis, and dental procedures on patients with hemophilia. There is a paucity of literature evaluating the use of TXA for hemostasis in patients on direct oral anticoagulants (DOACs).
Intravenous tranexamic acid decreases intraoperative transfusion requirements and does not increase incidence of symptomatic venous thromboembolic events in musculoskeletal sarcoma surgery. [2023]Tranexamic acid (TXA) is poorly studied in patients with bone and musculoskeletal sarcoma due to perceived increased risk of venous thromboembolism (VTE). This study aims to assess the safety and efficacy of intravenous (IV) TXA for patients undergoing surgical resection of primary bone or soft-tissue sarcoma.