Cyclophosphamide ToxicityNCT05886335
Influence of Timing PTCy in AlloSCT
An observational study of Cyclophosphamide Toxicity and Allogenic Haematopoetic Transplantation, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
Trial summary
Cyclophosphamide, administered after the infusion of haematopoietic progenitor cells, is used to prevent graft-versus-recipient disease (GVHD) in patients undergoing allogeneic haematopoietic stem cell transplantation (allogeneic HSCT) and has been shown to reduce the incidence of GVHD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cyclophosphamide Toxicity, Allogenic Haematopoetic Transplantation
- What is being tested?
- Cyclophosphamide
- How many people
- 180 participants
- Where
- 1 siteSpain
- Study dates
- 26 Jun 2023to 31 Jan 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients who received cyclophosphamide after haematopoietic progenitor transplantation, consecutively, at the HSCSP, between January 2014 and December 2022.
Who may be able to join
- Adult recipients (>18 years old) of Allo-SCT
- Allo SCT between January 1, 2014 and December 31, 2022
- PTCy dose 50 mg/kg x 2 days
Who cannot join
- Patients with no record of time of administration of PTCy
- PTCy dose of 30 mg/kg x 2 days
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of the Influence of Timing of Post-transplant Cyclophosphamide in Allogeneic Haematopoietic Stem Cell Transplant Patients.
Cyclophosphamide, administered after the infusion of haematopoietic progenitor cells, is used to prevent graft-versus-recipient disease (GVHD) in patients undergoing allogeneic haematopoietic stem cell transplantation (allogeneic HSCT) and has been shown to reduce the incidence of GVHD.
Cyclophosphamide can cause haemorrhagic cystitis as a result of the direct toxicity of its metabolite acrolein to the bladder mucosa or urothelium upon accumulation in the urine. Hyperhydration and the administration of mesna, which forms a non-urotoxic compound with acrolein, are among the most commonly used strategies to prevent this. The administration of cyclophosphamide in the morning is also recommended.
The protocol for post-transplant cyclophosphamide states that it should be started at least 72 hours (days +3 and +4) after haematopoietic progenitor infusion, but this interval can be extended to 84 hours (day +3.5). After reviewing the recommendations to reduce the risk of haemorrhagic cystitis, it was recommended to delay the infusion of cyclophosphamide to the early morning of days +4 and +5, although in reality, taking into account the hours since the infusion of haematopoietic progenitors, it would be days +3.5 and +4.5 instead of days +3 and +4 in the afternoon/evening. This change will mean a delay of 12 hours in the start of cyclophosphamide, so the investigators will refer to day +3.5 from the infusion of the haematopoietic precursors.
Read the detailed description
Cyclophosphamide administered after haematopoietic stem cell infusion is used for the prevention of graft-versus-recipient disease (GVHD) in patients undergoing allogeneic haematopoietic stem cell transplantation (allo-SCT) and has been shown to reduce the incidence of GVHD.
However, cyclophosphamide can cause haemorrhagic cystitis (HC) as one of the best known adverse effects. This is due to the direct toxicity of the cyclophosphamide metabolite, acrolein, to the bladder mucosa or urothelium as it accumulates in the urine. The incidence of HC can vary from 10 to 70% of patients and increases the number of days spent in hospital as well as morbidity and mortality after transplantation. Among the most common risk factors and causative agents, in addition to cyclophosphamide, are BK polyomavirus infections, with cyclophosphamide-induced HC often occurring within 72 hours of the administration of cyclophosphamide.
There are several strategies to prevent cyclophosphamide-induced HC, such as hyperhydration with saline and forcing diuresis with furosemide, alkalinisation of diuresis or administration of mesna, which forms a non-urotoxic complex with acrolein in the urinary tract and prevents tissue damage. However, further studies are needed to understand the best strategy to prevent HC, especially in the setting of allo-SCT.
In order to ensure proper hydration, to promote diuresis during the day and to reduce the time that acrolein is in contact with the mucosa, the administration of cyclophosphamide in the morning is recommended.
There are several strategies to prevent cyclophosphamide-induced HC, such as hyperhydration with saline and forcing diuresis with furosemide, alkalinisation of diuresis or administration of mesna, which forms a non-urotoxic complex with acrolein in the urinary tract and prevents tissue damage. However, further studies are needed to understand the best strategy to prevent HC, especially in the setting of allo-SCT.
In order to ensure proper hydration, to promote diuresis during the day and to reduce the time that acrolein is in contact with the mucosa, the administration of cyclophosphamide in the morning is recommended.
The usual protocol for the administration of cyclophosphamide (PTCy) after transplantation states that it should be started at least 72 hours (days +3 and +4) after the infusion of haematopoietic progenitors, but this interval can be extended to 84 hours (days +3.5) and the days of administration have been changed to days +3 and +5 with optimal results. In some patients, the infusion of haematopoietic precursors is carried out in the afternoon because of the need for nursing care. This meant that cyclophosphamide had to be administered in the evening, 72 hours after the infusion of the precursors. After review of the recommendations to reduce the risk of haemorrhagic cystitis, it was recommended that cyclophosphamide infusion be delayed in the morning on days +4 and +5, although in reality, taking into account the hours since haematopoietic progenitor infusion, these would be days +3.5 and +4.5 instead of days +3 and +4 in the afternoon/evening. This change means a 12-hour delay in the start of cyclophosphamide. Therefore, the investigators refer to day +3.5 from the infusion of haematopoietic progenitors.
- Being tested
- Cyclophosphamide
- Keywords
- haemorrhagic cystitis, cyclophosphamide, allogenic haematopoetic transplantation
- Medical subject headings
- Cystitis, Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Time of administration
| Study group | Role | What they receive |
|---|---|---|
| Cystitis hemorrhagic | Cystitis hemorrhagic grade II-III Receives: Drug: Cyclophosphamide | |
| Non Cystitis hemorrhagic | Non cystitis hemorrhagic or grade I Receives: Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence haemorrhagic cystitis Grade II-IV
To compare the incidence of grade II to IV haemorrhagic cystitis, according to the CTCAE classification, depending on the schedule of post-transplant cyclophosphamide administration in consecutive patients.
Measured: 6 months
Secondary outcomes (2)
GVHD acute and chronic
To compare the incidence of acute and chronic graft-versus-host disease.
Measured: 6 months
Mortality and relapsed
To compare the incidence of transplant-related mortality and recurrence.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2023
- Study start26 Jun 2023
- Primary completion30 Nov 2024
- Study completion31 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cyclophosphamide ToxicityStudies of the same condition, open and under way.
- More trials run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05886335
- Sponsor's protocol ID
- IIBSP-CFM-2023-45
- Status last verified
- Mar 2025
- First submitted
- 23 May 2023
- Last updated
- 24 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Influence of Timing of Post-transplant Cyclophosphamide in Allogeneic Haematopoietic Stem Cell Transplant Patients.
- ClinicalTrials.gov ID
- NCT05886335
- Acronym / sponsor ID
- IIBSP-CFM-2023-45
- Keywords
- haemorrhagic cystitis, cyclophosphamide, allogenic haematopoetic transplantation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Study start
- 26 Jun 2023 (actual)
- Primary completion
- 30 Nov 2024 (actual)
- Study completion
- 31 Jan 2025 (actual)
- First posted
- 2 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cyclophosphamide, administered after the infusion of haematopoietic progenitor cells, is used to prevent graft-versus-recipient disease (GVHD) in patients undergoing allogeneic haematopoietic stem cell transplantation (allogeneic HSCT) and has been shown to reduce the incidence of GVHD.
Cyclophosphamide can cause haemorrhagic cystitis as a result of the direct toxicity of its metabolite acrolein to the bladder mucosa or urothelium upon accumulation in the urine. Hyperhydration and the administration of mesna, which forms a non-urotoxic compound with acrolein, are among the most commonly used strategies to prevent this. The administration of cyclophosphamide in the morning is also recommended.
The protocol for post-transplant cyclophosphamide states that it should be started at least 72 hours (days +3 and +4) after haematopoietic progenitor infusion, but this interval can be extended to 84 hours (day +3.5). After reviewing the recommendations to reduce the risk of haemorrhagic cystitis, it was recommended to delay the infusion of cyclophosphamide to the early morning of days +4 and +5, although in reality, taking into account the hours since the infusion of haematopoietic progenitors, it would be days +3.5 and +4.5 instead of days +3 and +4 in the afternoon/evening. This change will mean a delay of 12 hours in the start of cyclophosphamide, so the investigators will refer to day +3.5 from the infusion of the haematopoietic precursors.
Detailed description
Cyclophosphamide administered after haematopoietic stem cell infusion is used for the prevention of graft-versus-recipient disease (GVHD) in patients undergoing allogeneic haematopoietic stem cell transplantation (allo-SCT) and has been shown to reduce the incidence of GVHD.
However, cyclophosphamide can cause haemorrhagic cystitis (HC) as one of the best known adverse effects. This is due to the direct toxicity of the cyclophosphamide metabolite, acrolein, to the bladder mucosa or urothelium as it accumulates in the urine. The incidence of HC can vary from 10 to 70% of patients and increases the number of days spent in hospital as well as morbidity and mortality after transplantation. Among the most common risk factors and causative agents, in addition to cyclophosphamide, are BK polyomavirus infections, with cyclophosphamide-induced HC often occurring within 72 hours of the administration of cyclophosphamide.
There are several strategies to prevent cyclophosphamide-induced HC, such as hyperhydration with saline and forcing diuresis with furosemide, alkalinisation of diuresis or administration of mesna, which forms a non-urotoxic complex with acrolein in the urinary tract and prevents tissue damage. However, further studies are needed to understand the best strategy to prevent HC, especially in the setting of allo-SCT.
In order to ensure proper hydration, to promote diuresis during the day and to reduce the time that acrolein is in contact with the mucosa, the administration of cyclophosphamide in the morning is recommended.
There are several strategies to prevent cyclophosphamide-induced HC, such as hyperhydration with saline and forcing diuresis with furosemide, alkalinisation of diuresis or administration of mesna, which forms a non-urotoxic complex with acrolein in the urinary tract and prevents tissue damage. However, further studies are needed to understand the best strategy to prevent HC, especially in the setting of allo-SCT.
In order to ensure proper hydration, to promote diuresis during the day and to reduce the time that acrolein is in contact with the mucosa, the administration of cyclophosphamide in the morning is recommended.
The usual protocol for the administration of cyclophosphamide (PTCy) after transplantation states that it should be started at least 72 hours (days +3 and +4) after the infusion of haematopoietic progenitors, but this interval can be extended to 84 hours (days +3.5) and the days of administration have been changed to days +3 and +5 with optimal results. In some patients, the infusion of haematopoietic precursors is carried out in the afternoon because of the need for nursing care. This meant that cyclophosphamide had to be administered in the evening, 72 hours after the infusion of the precursors. After review of the recommendations to reduce the risk of haemorrhagic cystitis, it was recommended that cyclophosphamide infusion be delayed in the morning on days +4 and +5, although in reality, taking into account the hours since haematopoietic progenitor infusion, these would be days +3.5 and +4.5 instead of days +3 and +4 in the afternoon/evening. This change means a 12-hour delay in the start of cyclophosphamide. Therefore, the investigators refer to day +3.5 from the infusion of haematopoietic progenitors.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cystitis hemorrhagic | – | Drug: CyclophosphamideCystitis hemorrhagic grade II-III |
| Non Cystitis hemorrhagic | – | Drug: CyclophosphamideNon cystitis hemorrhagic or grade I |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who received cyclophosphamide after haematopoietic progenitor transplantation, consecutively, at the HSCSP, between January 2014 and December 2022.
Key inclusion criteria (3 listed)
- Adult recipients (>18 years old) of Allo-SCT
- Allo SCT between January 1, 2014 and December 31, 2022
- PTCy dose 50 mg/kg x 2 days
Key exclusion criteria (2 listed)
- Patients with no record of time of administration of PTCy
- PTCy dose of 30 mg/kg x 2 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CyclophosphamideTime of administration | Drug | Cystitis hemorrhagic, Non Cystitis hemorrhagic |
Primary outcome
incidence haemorrhagic cystitis Grade II-IV
Time frame: 6 months
To compare the incidence of grade II to IV haemorrhagic cystitis, according to the CTCAE classification, depending on the schedule of post-transplant cyclophosphamide administration in consecutive patients.
2 secondary outcomes
GVHD acute and chronic
Time frame: 6 months
Mortality and relapsed
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
- Individual participant dataSharing planned: Undecided
Related trials for Cyclophosphamide Toxicity
RecruitingObservational study
Factors Affecting Post-transplant Cyclophosphamide (PTCy) Efficacy
Leukemia, Not Otherwise Specified, Leukemia, Other
Not yet recruitingPhase 3
Reduced Post-transplant Cyclophosphamide Dose in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation for Hematological Malignancies
GVHD - Graft-Versus-Host Disease, HSCT
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cyclophosphamide Toxicity and Allogenic Haematopoetic Transplantation, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
incidence haemorrhagic cystitis Grade II-IV (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2025.