REscuing Bone Marrow Function in Patients with AplaStic AnaEmia and Bone Marrow FaiLure Post AllogEneiC Transplantation 2
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.
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- 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;
- 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
Exclusion criteria
- 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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1PHASE2
Study ID
NCT06607367
Intervention or treatment
DRUG: Ruxolitinib (JAKAVI®)
DRUG: Eltrombopag (Revolade®)
Conditions
- Poor Graft Function
- Aplastic Anemia Idiopathic
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Research sites nearby
Closest Location:
The Royal Melbourne Hospital
Select from list below to view details:
The Royal Melbourne Hospital
Parkville, Victoria, Australia
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Who is running the clinical trial?
Melbourne Health
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Ruxolitinib and Eltrombopag
| Drug: Ruxolitinib (JAKAVI®), Drug: Eltrombopag (Revolade®) |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Complete Response at 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 | 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 | From study enrolment to study completion (maximum of 1 year per subject) |
Secondary Outcome
References
Clinical Trials Gov: REscuing Bone Marrow Function in Patients with AplaStic AnaEmia and Bone Marrow FaiLure Post AllogEneiC Transplantation 2Other trials to consider
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