Poor Graft FunctionPhase 1/2RESELECT2NCT06607367
REscuing Bone Marrow Function in Patients with AplaStic AnaEmia and Bone Marrow FaiLure Post AllogEneiC Transplantation 2
A Phase 1/2 study testing Ruxolitinib (JAKAVI®) and Eltrombopag (Revolade®) in people with Poor Graft Function and Aplastic Anemia Idiopathic, run by Melbourne Health at 1 site in Australia.
Trial summary
Allogeneic stem cell transplantation involves the transplanting of donor blood stem cells into a recipient, this is performed mainly for the treatment of blood cancers. The bone marrow is the organ that produces all blood cells and allogeneic stem cell transplantation results in the replacement of abnormal recipient… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Poor Graft Function, Aplastic Anemia Idiopathic
- What is being tested?
- Ruxolitinib (JAKAVI®) and Eltrombopag (Revolade®)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteAustralia
- Study dates
- 30 Oct 2024to 30 Oct 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- Patient must meet ALL of the following:
- Poor Graft function OR Relapsed/refractory AA
- Poor Graft Function defined as follows:≥95% donor chimerism at last reading OR ≥95% CD3 negative chimerism; ≥2 Lineage cytopenias defined as:
- Thrombocytopenia:
- 30x109 /L from D40-D60 OR
- 50 x10 9/L from D60 onwards; Neutropenia requiring filgrastim support at any time post D40; Hb less than 80g/L;
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- Relapsed /Refractory AA defined as: Relapse after stem cell transplant OR relapsed post/refractory to 1st line immunosuppression without an unrelated donor identified.
- Age ≥18
- ECOG performance status 0-1
- Life expectancy greater than 6 months
- Patient's written informed consent
Who cannot join
- Active Grade 3-4 acute GVHD
- Relapsed or progressive disease on screening bone marrow biopsy or most recent PET imaging.
- Active second malignancy currently requiring treatment
- Human Immuno-deficiency Virus (HIV) infection.
- Any coexisting medical or psychological condition that would preclude participation in the required study procedures.
- Female patients who are both lactating and breast-feeding or have a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1 before first dose of study drug
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Ashvind Prabahran contact
Australia1 site
The Royal Melbourne Hospital
Parkville, Victoria, 3050
David Ritchie, +6193427000, david.ritchie@mh.org.au
About this study
Allogeneic stem cell transplantation involves the transplanting of donor blood stem cells into a recipient, this is performed mainly for the treatment of blood cancers. The bone marrow is the organ that produces all blood cells and allogeneic stem cell transplantation results in the replacement of abnormal recipient bone marrow with donor blood cells as well as the production of donor immune cells from the donor bone marrow. The production of donor immune cells will hopefully lead to an immune response directed at any persisting cancerous cells leading to their eradication. As such, one of the key measures of success of a transplant is establishment of donor engraftment.
Engraftment is considered successful when the patient has normal blood cell counts on routine laboratory testing as well as confirmation that the blood cells are being produced by donor bone marrow cells. Confirming donor blood cell production is done by a process called chimerism. Poor graft function (PGF) is a complication of allogeneic stem cell transplantation related to engraftment, manifested by low blood counts despite complete donor chimerism. This has significant consequences for the patient leaving them susceptible to infection because of low white blood cells and bleeding because of low platelets (the cell components that are important for blood clotting). There is currently no established treatment for this condition and patients with this condition who do not recover have a poor survival.
Read more
Aplastic anaemia (AA) is a rare autoimmune condition that results in a patient's own immune system attacking important components of their bone marrow resulting in low blood counts. The current treatments for AA include suppressing the immune system or a bone marrow transplant, however long term survival for patients who do not respond to these treatments or relapse is poor and more effective treatments are required.
There is emerging evidence that demonstrates that the components of the immune system are dysfunctional and result in excessive immune activation resulting in suppression of the bone marrow characteristic of PGF. Similar features of immune dysfunction has been demonstrated in AA. Ruxolitinib is a drug that may be able to reduce this excessive immune activation. Eltrombopag is a drug that has been shown to stimulate the production of blood cells. The aim of this study is to evaluate whether the combination of ruxolitinib and eltrombopag is safe and effective in the treatment of PGF and AA.
Read the detailed description
Study Overview:
This is a, multi-centre, single active arm with historic control arm, phase I/II study that will assess the safety and efficacy of ruxolitinib and eltrombopag in patients with relapse/refractory AA and PGF post alloSCT.
Efficacy will be evaluated using the study endpoints. The study will consist of screening and enrolment (up to 28 days), treatment (12 weeks) and follow up (up to 9 months post enrolment). Therefore, the maximum time on study for a single patient will be a maximum of 12 months.
There will be an initial safety lead in phase of 10 participants. Adverse events will be evaluated by the SMC who will then decide whether the study will proceed to the complete enrolment of 20 participants based on the safety analysis
Treatment:
Upon enrolment, patients in the intervention arm will commence the following treatment: Ruxolitinib at a dose of 10mg BD and Eltrombopag at a dose of 50mg.
Dose adjustments may be required based on lack of efficacy, or thrombocytopenia.
- Conditions
- Poor Graft Function, Aplastic Anemia Idiopathic
- Being tested
- Ruxolitinib (JAKAVI®), Eltrombopag (Revolade®)
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ruxolitinib (JAKAVI®)Drug
Initial starting dose will be 10mg BD
Eltrombopag (Revolade®)Drug
Initial starting dose will be 50mg daily
| Study group | Role | What they receive |
|---|---|---|
| Ruxolitinib and Eltrombopag | Experimental | Ruxolitinib at a dose of 10mg BD and Eltrombopag at a dose of 50mg Dose adjustments may be required based on lack of efficacy, or thrombocytopenia may occur as per the study protocol . Receives: Drug: Ruxolitinib (JAKAVI®); Drug: Eltrombopag (Revolade®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response at 12 weeks
Number of patients with Complete Response (CR) at 12 weeks defined as:
- Neutrophils greater than or equal to 1.5x10^9/L
- Platelets greater than or equal to 100x10^9/L without use of transfusions or cytokine support
Measured: 12 weeks
Grade 2 or Higher Non-Haematologic Toxicity
Rates of grade 2 or higher non haematologic toxicity as graded by the national cancer institute toxicity criteria version 5
Measured: From study enrolment to study completion (maximum of 1 year per subject)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2024
- Study start30 Oct 2024 (estimated)
- Primary completion30 Oct 2025 (estimated)
- Study completion30 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Poor Graft FunctionStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single group study with historic control
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Melbourne Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06607367
- Sponsor's protocol ID
- 2024.231
- Acronym
- RESELECT2
- Status last verified
- Sep 2024
- First submitted
- 15 Sep 2024
- Last updated
- 23 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual patient data will not be shared. Aggregate patient data and final results will be presented in the final report
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REscuing Bone Marrow Function in Patients with AplaStic AnaEmia and Bone Marrow FaiLure Post AllogEneiC Transplantation 2
- ClinicalTrials.gov ID
- NCT06607367
- Acronym / sponsor ID
- RESELECT2 / 2024.231
- Conditions
- Poor Graft Function, Aplastic Anemia Idiopathic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Melbourne HealthUniversity, hospital or other
- Study start
- 30 Oct 2024 (estimated)
- Primary completion
- 30 Oct 2025 (estimated)
- Study completion
- 30 Oct 2026 (estimated)
- First posted
- 23 Sep 2024 (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.
Allogeneic stem cell transplantation involves the transplanting of donor blood stem cells into a recipient, this is performed mainly for the treatment of blood cancers. The bone marrow is the organ that produces all blood cells and allogeneic stem cell transplantation results in the replacement of abnormal recipient bone marrow with donor blood cells as well as the production of donor immune cells from the donor bone marrow. The production of donor immune cells will hopefully lead to an immune response directed at any persisting cancerous cells leading to their eradication. As such, one of the key measures of success of a transplant is establishment of donor engraftment.
Engraftment is considered successful when the patient has normal blood cell counts on routine laboratory testing as well as confirmation that the blood cells are being produced by donor bone marrow cells. Confirming donor blood cell production is done by a process called chimerism. Poor graft function (PGF) is a complication of allogeneic stem cell transplantation related to engraftment, manifested by low blood counts despite complete donor chimerism. This has significant consequences for the patient leaving them susceptible to infection because of low white blood cells and bleeding because of low platelets (the cell components that are important for blood clotting). There is currently no established treatment for this condition and patients with this condition who do not recover have a poor survival.
Aplastic anaemia (AA) is a rare autoimmune condition that results in a patient's own immune system attacking important components of their bone marrow resulting in low blood counts. The current treatments for AA include suppressing the immune system or a bone marrow transplant, however long term survival for patients who do not respond to these treatments or relapse is poor and more effective treatments are required.
There is emerging evidence that demonstrates that the components of the immune system are dysfunctional and result in excessive immune activation resulting in suppression of the bone marrow characteristic of PGF. Similar features of immune dysfunction has been demonstrated in AA. Ruxolitinib is a drug that may be able to reduce this excessive immune activation. Eltrombopag is a drug that has been shown to stimulate the production of blood cells. The aim of this study is to evaluate whether the combination of ruxolitinib and eltrombopag is safe and effective in the treatment of PGF and AA.
Detailed description
Study Overview:
This is a, multi-centre, single active arm with historic control arm, phase I/II study that will assess the safety and efficacy of ruxolitinib and eltrombopag in patients with relapse/refractory AA and PGF post alloSCT.
Efficacy will be evaluated using the study endpoints. The study will consist of screening and enrolment (up to 28 days), treatment (12 weeks) and follow up (up to 9 months post enrolment). Therefore, the maximum time on study for a single patient will be a maximum of 12 months.
There will be an initial safety lead in phase of 10 participants. Adverse events will be evaluated by the SMC who will then decide whether the study will proceed to the complete enrolment of 20 participants based on the safety analysis
Treatment:
Upon enrolment, patients in the intervention arm will commence the following treatment: Ruxolitinib at a dose of 10mg BD and Eltrombopag at a dose of 50mg.
Dose adjustments may be required based on lack of efficacy, or thrombocytopenia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single group study with historic control
| Arm | Type | Receives |
|---|---|---|
| Ruxolitinib and Eltrombopag | Experimental | Drug: Ruxolitinib (JAKAVI®), Drug: Eltrombopag (Revolade®)Ruxolitinib at a dose of 10mg BD and Eltrombopag at a dose of 50mg Dose adjustments may be required based on lack of efficacy, or thrombocytopenia may occur as per the study protocol . |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Poor Graft function OR Relapsed/refractory AA
- Age ≥18
- ECOG performance status 0-1
- Life expectancy greater than 6 months
- Patient's written informed consent
Key exclusion criteria (6 listed)
- Active Grade 3-4 acute GVHD
- Relapsed or progressive disease on screening bone marrow biopsy or most recent PET imaging.
- Active second malignancy currently requiring treatment
- Human Immuno-deficiency Virus (HIV) infection.
- Any coexisting medical or psychological condition that would preclude participation in the required study procedures.
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 |
|---|---|---|
| Ruxolitinib (JAKAVI®)Initial starting dose will be 10mg BD | Drug | Ruxolitinib and Eltrombopag |
| Eltrombopag (Revolade®)Initial starting dose will be 50mg daily | Drug | Ruxolitinib and Eltrombopag |
Primary outcome
Complete Response at 12 weeks
Time frame: 12 weeks
Number of patients with Complete Response (CR) at 12 weeks defined as: 1. Neutrophils greater than or equal to 1.5x10^9/L 2. Platelets greater than or equal to 100x10^9/L without use of transfusions or cytokine support
Grade 2 or Higher Non-Haematologic Toxicity
Time frame: From study enrolment to study completion (maximum of 1 year per subject)
Rates of grade 2 or higher non haematologic toxicity as graded by the national cancer institute toxicity criteria version 5
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
- Individual participant dataSharing planned: No. Individual patient data will not be shared. Aggregate patient data and final results will be presented in the final report
Related trials for Poor Graft Function
Not yet recruitingPhase 1/2
Anakinra for Prevention of Poor Graft Function in MDS Allo-HSCT
Poor Graft Function, Myelodysplastic Syndromes
Recruiting
CD34+ Selected Stem Cell for Poor Graft Function or Graft Failure
Graft Failure, Poor Graft Function
Recruiting
Compassionate Access of the Miltenyi Device for CD34+ Cell Selection
Blood And Marrow Transplantation
RecruitingPhase 1
The Safety and Efficacy of Umbilical Cord Blood Mononuclear Cells in Patients With Secondary Poor Graft Function After Hematopoietic Stem Cell Transplantation
Poor Graft Function
Not yet recruitingPhase 4
Mesenchymal Stem Cells for Treatment of Poor Graft Function After Allogeneic Hematopoietic Stem Cell Transplantation
MSC
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.
Ashvind Prabahran contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ruxolitinib (JAKAVI®) and Eltrombopag (Revolade®) in people with Poor Graft Function and Aplastic Anemia Idiopathic, run by Melbourne Health at 1 site in Australia.
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 11 inclusion and 6 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: opening soon, as of the sponsor's last update on 23 Sep 2024. 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 Australia. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Ritchie (+61393427000, david.ritchie@mh.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Response at 12 weeks (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 23 Sep 2024.