Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT06607367

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.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Poor Graft Function Anemia Anemia, Aplastic Aplastic Anemia Idiopathic Bone Marrow Diseases Bone Marrow Failure Disorders Hematologic Diseases Hemic and Lymphatic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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;
  • 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

Treatment and study plan

Ruxolitinib (JAKAVI®)

Drug

Initial starting dose will be 10mg BD

Eltrombopag (Revolade®)

Drug

Initial starting dose will be 50mg daily

Primary outcomes

  1. Complete Response at 12 weeks

    Time frame: 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

  2. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Ashvind Prabahran

CONTACT

[email protected]

David Ritchie

CONTACT

[email protected]

+61393427000

Sponsors and collaborators

Lead sponsor

Melbourne Health

Other

Registry information

Acronym: RESELECT2

Important dates

Study start
2024
Primary completion
2025
Study completion
2026
First posted
Sep 23, 2024
Registry last updated
Sep 23, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.