Tranexamic Acid for Blood Cancer Patients Undergoing Stem Cell Transplant

(PATH Trial)

Recruiting at 10 trial locations

Overseen By Alan Tinmouth, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ottawa Hospital Research Institute

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Thrombotic events, Angina, Renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 4 weeks

662 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{6 7 8 9 10}

How 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. ^{1 3 11 12 13}

Eligibility 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.

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

Treatment Details

Interventions

• Tranexamic Acid

Trial Overview 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.

Participant Groups

Group I: Prophylactic Tranexamic Acid Experimental Treatment 1 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 Transfusion Active Control 1 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 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

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Alberta Cancer Foundation

Collaborator

Trials

18

Recruited

5,600+

Findings from Research

In a study of 282 cancer patients undergoing hip or knee arthroplasty, the use of tranexamic acid (TXA) did not increase the risk of complications such as venous thromboembolism within 90 days or 1 year, suggesting it is safe for this population.

TXA was associated with a trend towards lower risk of complications, indicating that it may be beneficial for reducing blood loss in cancer patients undergoing surgery without compromising their safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid in patients with current or former cancer undergoing hip and knee arthroplasty. Varady, NH., Chen, AF., Drayer, NJ., et al.[2021]

In a study of 108 patients undergoing total shoulder arthroplasty, intravenous tranexamic acid (TXA) significantly reduced postoperative blood loss compared to a placebo, with an average loss of 1100.9 mL in the TXA group versus 1274.5 mL in the placebo group.

TXA also resulted in lower hemoglobin loss without any patients requiring a blood transfusion, indicating its efficacy and safety in managing blood loss during shoulder surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid reduces blood loss after primary shoulder arthroplasty: a double-blind, placebo-controlled, prospective, randomized controlled trial. Cvetanovich, GL., Fillingham, YA., O'Brien, M., et al.[2022]

Tranexamic acid (TxA) significantly reduces the volume of hematomas after total knee arthroplasty (TKA), with a decrease from 526 mL in the control group to 337 mL in the TxA group, indicating its efficacy in minimizing blood loss.

Despite the reduction in hematoma volume, TxA did not lead to a significant decrease in morphine consumption for pain management or improve rehabilitation outcomes within the first six months post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tranexamic acid reduces haematomas but not pain after total knee arthroplasty]. Chevet, I., Remérand, F., Couvret, C., et al.[2013]

A survey of 73 hematology clinicians in the Netherlands revealed that prophylactic platelet transfusions are commonly used in outpatients with acute leukemia and myelodysplastic syndrome, with 87%-98% of respondents supporting their use.

Tranexamic acid (TXA) is mainly prescribed when there is a tendency to bleed, with 71%-88% of clinicians indicating its use, highlighting a need for more evidence-based guidelines on anti-bleeding measures in patients with severe thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet transfusion and tranexamic acid to prevent bleeding in outpatients with a hematological disease: A Dutch nationwide survey. Cornelissen, LL., Caram-Deelder, C., Meier, RT., et al.[2021]

In a study of 126 patients undergoing surgery for aggressive bone tumors, those who received tranexamic acid (TXA) ambulated significantly further and participated longer in physical therapy sessions compared to those who did not receive TXA, especially on postoperative Days 1 and 2.

The increased ambulation associated with TXA administration correlated with a shorter hospital stay and a higher likelihood of being discharged home, highlighting its potential benefits in postoperative recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid improves early postoperative mobilization in cancer patients undergoing endoprosthetic reconstruction. Haase, DR., Mersereau, EJ., Kimbrel, B., et al.[2022]

In a study involving 34 adult patients with severe aplastic anemia undergoing haplo-identical stem cell transplantation, a conditioning regimen using 600 cGy total body irradiation, fludarabine, and intermediate-dose rabbit ATG resulted in successful primary engraftment for all patients.

The group receiving the lower dose of total body irradiation (600 cGy) showed a trend towards better overall survival (91.7%) and graft-versus-host disease (GVHD)-free survival (78.4%) compared to those receiving higher doses, indicating a potentially safer and more effective approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Lee, SE., Park, SS., Jeon, YW., et al.[2019]

The maximum tolerated dose (MTD) of thiotepa (TT) in combination with busulfan and etoposide for children with solid tumors was determined to be 750 mg/m², with manageable toxicity observed in the study.

All 19 patients showed hematological recovery after treatment, with no treatment-related deaths, indicating that this high-dose chemotherapy regimen is feasible and tolerable for further investigation in children with poor-prognosis solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of high-dose thiotepa with busulfan, etoposide, and autologous stem cell support in children with disseminated solid tumors. Pession, A., Prete, A., Locatelli, F., et al.[2019]

In a Phase I trial involving 19 children with refractory malignancies, thiotepa (TT) was found to be safely administered at a maximum tolerated bolus dose of 65 mg/m2, with reversible myelosuppression identified as the main dose-limiting toxicity.

Thiotepa and its active metabolite, tepa (TP), demonstrated excellent penetration into the cerebrospinal fluid (CSF), suggesting potential efficacy for treating central nervous system tumors, warranting further Phase II studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic evaluation of thiotepa in the cerebrospinal fluid and plasma of pediatric patients: evidence for dose-dependent plasma clearance of thiotepa. Heideman, RL., Cole, DE., Balis, F., et al.[2023]

Using low-dose single fraction total body irradiation (TBI) (550 cGy) with cyclophosphamide (CY) as a conditioning treatment for pediatric hematologic malignancies resulted in a 1-year overall survival rate of 60% and a disease-free survival rate of 47% among 55 children, indicating its efficacy in this high-risk population.

The treatment was generally well tolerated, with manageable acute toxicities, including 18% experiencing severe mucositis and an 11% rate of invasive infections, suggesting that this approach may reduce the severe complications commonly associated with fractionated TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early outcomes after allogeneic hematopoietic SCT in pediatric patients with hematologic malignancies following single fraction TBI. Druley, TE., Hayashi, R., Mansur, DB., et al.[2021]

In a clinical trial involving 36 patients with advanced recurrent breast cancer, weekly Taxol (TXL) therapy showed a response rate of 45.2%, indicating its efficacy as a treatment option.

The treatment was generally safe, with most adverse reactions being mild, and only a few patients experiencing significant hematotoxicity, suggesting that TXL can be administered in an outpatient setting with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of weekly taxol (TXL) for advanced recurrent breast cancer evaluated in a multi-center cooperative clinical trial]. Nishi, T., Yamanaka, E., Yamasaki, M., et al.[2015]

A systematic review and meta-analysis of four studies involving 2,347 trauma patients showed that prehospital administration of tranexamic acid (TXA) significantly reduces early mortality (within 24 hours) compared to no TXA, with an odds ratio of 0.60.

The use of TXA did not increase the risk of venous thromboembolism, indicating it is a safe intervention for managing bleeding in trauma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of prehospital TXA on mortality among bleeding trauma patients: A systematic review and meta-analysis. Almuwallad, A., Cole, E., Ross, J., et al.[2023]

Tranexamic acid (TXA) was successfully used to achieve hemostasis in a 72-year-old male patient on rivaroxaban, who experienced persistent bleeding after a biopsy, demonstrating its potential effectiveness in patients on direct oral anticoagulants (DOACs).

The intervention was simple, cost-effective, and required minimal resources, providing a novel approach to manage uncontrollable bleeding in anticoagulated patients when traditional methods were ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Tranexamic Acid for Hemostasis of an Oral Bleed in a Patient on a Direct Oral Anticoagulant. Boccio, E., Hultz, K., Wong, AH.[2022]

In a study of 98 patients undergoing surgical resection for bone or soft-tissue sarcoma, intravenous tranexamic acid (TXA) was found to significantly reduce the need for intraoperative blood transfusions and the amount of blood transfused, indicating its efficacy in managing bleeding during surgery.

Importantly, no patients receiving TXA experienced venous thromboembolism (VTE), suggesting that TXA can be safely used in this patient population without increasing the risk of serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous tranexamic acid decreases intraoperative transfusion requirements and does not increase incidence of symptomatic venous thromboembolic events in musculoskeletal sarcoma surgery. Hess, MC., Andrews, NA., Crowley, B., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tranexamic acid in patients with current or former cancer undergoing hip and knee arthroplasty. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Tranexamic acid reduces blood loss after primary shoulder arthroplasty: a double-blind, placebo-controlled, prospective, randomized controlled trial. [2022]

3. France pubmed.ncbi.nlm.nih.gov

[Tranexamic acid reduces haematomas but not pain after total knee arthroplasty]. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Platelet transfusion and tranexamic acid to prevent bleeding in outpatients with a hematological disease: A Dutch nationwide survey. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Tranexamic acid improves early postoperative mobilization in cancer patients undergoing endoprosthetic reconstruction. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

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]

7. United States pubmed.ncbi.nlm.nih.gov

Phase I study of high-dose thiotepa with busulfan, etoposide, and autologous stem cell support in children with disseminated solid tumors. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

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]

9. England pubmed.ncbi.nlm.nih.gov

Early outcomes after allogeneic hematopoietic SCT in pediatric patients with hematologic malignancies following single fraction TBI. [2021]

10. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of weekly taxol (TXL) for advanced recurrent breast cancer evaluated in a multi-center cooperative clinical trial]. [2015]

11. United States pubmed.ncbi.nlm.nih.gov

The impact of prehospital TXA on mortality among bleeding trauma patients: A systematic review and meta-analysis. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Topical Tranexamic Acid for Hemostasis of an Oral Bleed in a Patient on a Direct Oral Anticoagulant. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Intravenous tranexamic acid decreases intraoperative transfusion requirements and does not increase incidence of symptomatic venous thromboembolic events in musculoskeletal sarcoma surgery. [2023]