Transplant-Associated Thrombotic MicroangiopathyPhase 2NCT06182410
Defibrotide Prophylaxis of Transplant Associated-Thrombotic Microangiopathy for Neuroblastoma
A Phase 2 study testing Defibrotide in people with Transplant-Associated Thrombotic Microangiopathy and Neuroblastoma, run by University of California, San Francisco.
Trial summary
This phase II trial tests how well defibrotide works in preventing transplant-associated thrombotic microangiopathy (TA-TMA) in patients with high-risk neuroblastoma undergoing tandem transplants (hematopoietic stem cell transplant [HSCT]). TMA is a potential life-threatening complication of stem cell transplant. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Transplant-Associated Thrombotic Microangiopathy, Neuroblastoma, High-risk Neuroblastoma
- What is being tested?
- Defibrotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2024to 31 May 2027
- Phase
- Phase 2
- 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 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: 1 - < 18 years old.
- Participants must have high-risk neuroblastoma according to Children's Oncology Group (COG) risk classification at the time of initial diagnosis. Participants who were initially considered low or intermediate risk, but then reclassified as high risk are also eligible.
- Participants may have had salvage therapies (i.e., meta-iodobenzylguanidine (MIBG), dinutuximab) after induction but cannot have progressive disease at start of 4.
- Planned tandem transplants with conditioning with cyclophosphamide-thiotepa and carboplatin-etoposide-melphalan on, or as per, NCT03126916 (ANBL1531) or other tandem-containing COG high-risk neuroblastoma trials.
- Participants may be enrolled in upfront neuroblastoma protocol, but this is not required.
- Upfront MIBG or other therapies is not a contraindication.
- Organ function per institutional standard of care (SOC) guiding clearance for autologous HSCT.
- Written informed consent (and assent when applicable) obtained from participant or participant's legal representative and ability for subject to comply with the requirements of the study.
Who cannot join
- Life expectancy < 6 months.
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
- Known bleeding diathesis or bleeding risk deemed by the treating physician to be a contraindication to administration of defibrotide or on concomitant therapeutic anticoagulation. Administration of heparin and/or alteplase for central line maintenance is allowed.
About this study
Official title: Defibrotide Prophylaxis of Transplant Associated-Thrombotic Microangiopathy in Patients With High-Risk Neuroblastoma Receiving Tandem Transplants
This phase II trial tests how well defibrotide works in preventing transplant-associated thrombotic microangiopathy (TA-TMA) in patients with high-risk neuroblastoma undergoing tandem transplants (hematopoietic stem cell transplant [HSCT]). TMA is a potential life-threatening complication of stem cell transplant. TMA is a possible side effect of the chemotherapy (conditioning regimen) patients receive to help treat high-risk neuroblastoma, because these medicines can sometimes damage the blood vessel walls in the body. This damage leads to formation of tiny blood clots in organs, especially the kidney. This then causes organ damage and leads to problems with how they function. This study may help researchers learn how defibrotide may help prevent TMA before it starts, or help treat it once it starts among patients with high-risk neuroblastoma undergoing tandem transplants.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine if administration of prophylactic defibrotide sodium (defibrotide) will prevent the development of TA-TMA in participants with high-risk neuroblastoma receiving tandem transplants compared to historic controls.
SECONDARY OBJECTIVES:
- To evaluate the efficacy of defibrotide in the prevention of severe TA-TMA, as defined by any TA-TMA with one or more of the following complications:
Ia. Renal failure requiring dialysis; Ib. Pleural or pericardial effusion requiring any surgical intervention; Ic. Central nervous system dysfunction, including seizure, posterior reversible encephalopathy syndrome (PRES); Id. Pulmonary hypertension; Ie. Biopsy-proven gastrointestinal involvement with bleeding; If. Death not related to relapse of underlying neuroblastoma; II. To determine the incidence of grade ≥ 3 hemorrhage (per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) in participants on prophylactic defibrotide (grade 3 hemorrhage = transfusion indicated; invasive intervention indicated; hospitalization).
EXPLORATORY OBJECTIVES:
- To evaluate the incidence of hepatic sinusoidal obstructive syndrome (SOS) grade >= 2 (per Cairo criteria) with first and second HSCT.
II. To evaluate the percentage of patients who go on to second transplant compared to historic controls.
III. To evaluate median time in days to start of subsequent therapy (radiation and immunotherapy) and percent of patients who have delays compared to historic controls.
OUTLINE:
Participants receive defibrotide intravenously (IV) over 2 hours every 6 hours (Q6H) on days -8 to +21 during their first and second HSCT in the absence of unacceptable toxicity. After completion of study treatment, participants are followed until day +42 after second transplant and then every 2 weeks until 6 months after first HSCT.
- Conditions
- Transplant-Associated Thrombotic Microangiopathy, Neuroblastoma, High-risk Neuroblastoma, Thrombotic Microangiopathies
- Being tested
- Defibrotide
- Medical subject headings
- Neuroblastoma, Thrombotic Microangiopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DefibrotideDrug
Also called Noravid
Given intravenously (IV)
| Study group | Role | What they receive |
|---|---|---|
| Supportive Care (defibrotide) | Experimental | Participants receive defibrotide IV over 2 hours every six hours on days -8 to +21 during the first and second rounds of Hematopoietic stem-cell transplantation (HSCT). Receives: Drug: Defibrotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of transplant-associated thrombotic microangiopathy (TA-TMA)
The cumulative incidence of TA-TMA in participants will be compared to historical controls. The historic controls will be participants with high-risk neuroblastoma who underwent planned tandem transplant at University of California San Francisco (UCSF) between 2017 and 2023.
Measured: Up to1 year
Secondary outcomes (1)
Cumulative incidence of severe TA-TMA
The cumulative incidence of severe TA-TMA in the patients enrolled on study compared to historical controls.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2023
- Study start1 Aug 2024 (estimated)
- Primary completion31 May 2027 (estimated)
- Study completion31 May 2027 (estimated)
Why it stopped: Industry sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transplant-Associated Thrombotic MicroangiopathyStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Christine Higham, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06182410
- Sponsor's protocol ID
- 230822
- Other IDs
- NCI-2023-10277
- Status last verified
- Aug 2024
- First submitted
- 13 Dec 2023
- Last updated
- 7 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defibrotide Prophylaxis of Transplant Associated-Thrombotic Microangiopathy in Patients With High-Risk Neuroblastoma Receiving Tandem Transplants
- ClinicalTrials.gov ID
- NCT06182410
- Acronym / sponsor ID
- 230822
- Conditions
- Transplant-Associated Thrombotic Microangiopathy, Neuroblastoma, High-risk Neuroblastoma, Thrombotic Microangiopathies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Industry sponsor decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Study start
- 1 Aug 2024 (estimated)
- Primary completion
- 31 May 2027 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 26 Dec 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.
This phase II trial tests how well defibrotide works in preventing transplant-associated thrombotic microangiopathy (TA-TMA) in patients with high-risk neuroblastoma undergoing tandem transplants (hematopoietic stem cell transplant [HSCT]). TMA is a potential life-threatening complication of stem cell transplant. TMA is a possible side effect of the chemotherapy (conditioning regimen) patients receive to help treat high-risk neuroblastoma, because these medicines can sometimes damage the blood vessel walls in the body. This damage leads to formation of tiny blood clots in organs, especially the kidney. This then causes organ damage and leads to problems with how they function. This study may help researchers learn how defibrotide may help prevent TMA before it starts, or help treat it once it starts among patients with high-risk neuroblastoma undergoing tandem transplants.
Detailed description
PRIMARY OBJECTIVE:
- To determine if administration of prophylactic defibrotide sodium (defibrotide) will prevent the development of TA-TMA in participants with high-risk neuroblastoma receiving tandem transplants compared to historic controls.
SECONDARY OBJECTIVES:
- To evaluate the efficacy of defibrotide in the prevention of severe TA-TMA, as defined by any TA-TMA with one or more of the following complications:
Ia. Renal failure requiring dialysis; Ib. Pleural or pericardial effusion requiring any surgical intervention; Ic. Central nervous system dysfunction, including seizure, posterior reversible encephalopathy syndrome (PRES); Id. Pulmonary hypertension; Ie. Biopsy-proven gastrointestinal involvement with bleeding; If. Death not related to relapse of underlying neuroblastoma; II. To determine the incidence of grade ≥ 3 hemorrhage (per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) in participants on prophylactic defibrotide (grade 3 hemorrhage = transfusion indicated; invasive intervention indicated; hospitalization).
EXPLORATORY OBJECTIVES:
- To evaluate the incidence of hepatic sinusoidal obstructive syndrome (SOS) grade >= 2 (per Cairo criteria) with first and second HSCT.
II. To evaluate the percentage of patients who go on to second transplant compared to historic controls.
III. To evaluate median time in days to start of subsequent therapy (radiation and immunotherapy) and percent of patients who have delays compared to historic controls.
OUTLINE:
Participants receive defibrotide intravenously (IV) over 2 hours every 6 hours (Q6H) on days -8 to +21 during their first and second HSCT in the absence of unacceptable toxicity. After completion of study treatment, participants are followed until day +42 after second transplant and then every 2 weeks until 6 months after first HSCT.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Supportive Care (defibrotide) | Experimental | Drug: DefibrotideParticipants receive defibrotide IV over 2 hours every six hours on days -8 to +21 during the first and second rounds of Hematopoietic stem-cell transplantation (HSCT). |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Age: 1 - < 18 years old.
- Participants must have high-risk neuroblastoma according to Children's Oncology Group (COG) risk classification at the time of initial diagnosis. Participants who were initially considered low or intermediate risk, but then reclassified as high risk are also eligible.
- Participants may have had salvage therapies (i.e., meta-iodobenzylguanidine (MIBG), dinutuximab) after induction but cannot have progressive disease at start of 4.
- Planned tandem transplants with conditioning with cyclophosphamide-thiotepa and carboplatin-etoposide-melphalan on, or as per, NCT03126916 (ANBL1531) or other tandem-containing COG high-risk neuroblastoma trials.
- Participants may be enrolled in upfront neuroblastoma protocol, but this is not required.
Key exclusion criteria (4 listed)
- Life expectancy < 6 months.
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
- Known bleeding diathesis or bleeding risk deemed by the treating physician to be a contraindication to administration of defibrotide or on concomitant therapeutic anticoagulation. Administration of heparin and/or alteplase for central line maintenance is allowed.
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 |
|---|---|---|
| DefibrotideAlso: NoravidGiven intravenously (IV) | Drug | Supportive Care (defibrotide) |
Primary outcome
Cumulative incidence of transplant-associated thrombotic microangiopathy (TA-TMA)
Time frame: Up to1 year
The cumulative incidence of TA-TMA in participants will be compared to historical controls. The historic controls will be participants with high-risk neuroblastoma who underwent planned tandem transplant at University of California San Francisco (UCSF) between 2017 and 2023.
1 secondary outcome
Cumulative incidence of severe TA-TMA
Time frame: Up to 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2024.
- Individual participant dataSharing planned: No
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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.
Christine Higham, MD principal investigator
University of California, San Francisco
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Defibrotide in people with Transplant-Associated Thrombotic Microangiopathy and Neuroblastoma, run by University of California, San Francisco.
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 8 inclusion and 4 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: withdrawn, as of the sponsor's last update on 7 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Cumulative incidence of transplant-associated thrombotic microangiopathy (TA-TMA) (time frame: Up to1 year). 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 7 Aug 2024.