Ruxolitinib + Stem Cell Transplant for Acute Myeloid Leukemia

Recruiting at 5 trial locations

Overseen By Gabriella Hobbs, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Antibiotics, Antifungals, Antivirals

Disqualifiers: Prior HSCT, Organ dysfunction, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

64 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are receiving MDS-directed therapy, you must stop it at least 2 weeks before starting the trial's conditioning treatment.

What data supports the effectiveness of the drug Ruxolitinib in combination with stem cell transplant for treating Acute Myeloid Leukemia?

Ruxolitinib has shown effectiveness in reducing symptoms and improving outcomes in conditions like myelofibrosis and graft versus host disease, which involve similar biological pathways. This suggests it might also help improve outcomes when used with stem cell transplants in other blood-related conditions. ^{1 2 3 4 5}

Is ruxolitinib generally safe for humans?

Ruxolitinib has been used in patients with graft-versus-host disease (GVHD) and myelofibrosis, showing some serious side effects like infections, sepsis (a severe infection), and respiratory failure, but it is generally considered tolerable in these conditions. ^{1 2 6 7 8}

How does the drug Ruxolitinib differ from other treatments for acute myeloid leukemia?

Ruxolitinib is unique because it is a JAK1/2 inhibitor that has shown effectiveness in reducing complications like graft-versus-host disease (GVHD) when used with stem cell transplants, which is not a standard approach for acute myeloid leukemia. This combination aims to improve transplant outcomes by reducing immune-related complications. ^{1 2 8 9 10}

What is the purpose of this trial?

This research study is studying a drug that may help decrease the chances of relapse after Allogeneic Stem Cell transplantation for Acute Myeloid Leukemia. The name of the study drug involved in this study is: • Ruxolitinib

Research Team

Gabriell Hobbs, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults aged 60-80 with Acute Myeloid Leukemia (AML) in remission, or Myelodysplastic Syndromes (MDS), who are about to receive a stem cell transplant from a fully matched donor. Participants must be healthy enough for the procedure and not have other cancers (except certain skin cancers or cervical cancer in situ), severe infections, significant heart disease, HIV, or previous allogeneic HSCT.

Inclusion Criteria

My AML is in the first complete remission.

Must be able to understand and sign an informed consent document

I am between 60 and 80 years old.

Exclusion Criteria

My organ functions are within normal ranges.

I have a history of heart failure or known heart problems.

I am on medication for a long-term or active infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ruxolitinib following allogeneic stem cell transplantation. Ruxolitinib is administered orally 2 times per day at a fixed dose. Each study treatment cycle lasts 28 days, up to 24 cycles.

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival.

5 years

Treatment Details

Interventions

• Ruxolitinib

Trial Overview The study tests Ruxolitinib's effectiveness in reducing relapse risk after Allogeneic Stem Cell transplantation for AML. Patients will undergo reduced intensity conditioning therapy before receiving stem cells from an HLA-matched donor and will take Ruxolitinib alongside standard graft-versus-host disease prevention.

Participant Groups

Group I: Ruxolitinib Experimental Treatment 1 Intervention

Following a standard of care allogeneic stem cell transplantation, participants will be started on Ruxolitinib. Ruxolitinib is administered orally 2 times per day at a fixed dose. Each study treatment cycle lasts 28 days. Up to 24 cycles.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Vanderbilt University

Collaborator

Trials

714

Recruited

6,143,000+

Ohio State University

Collaborator

Trials

891

Recruited

2,659,000+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

Findings from Research

Ruxolitinib, an oral JAK1/2 inhibitor, is effective in reducing spleen size and symptom burden in patients with intermediate and high-risk myelofibrosis, making it a valuable treatment option before hematopoietic stem cell transplantation (HSCT).

The impact of ruxolitinib on HSCT outcomes is not well understood, and there is significant variability in how it is used in patients transitioning to HSCT, highlighting the need for more research to guide treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peritransplantation Use of Ruxolitinib in Myelofibrosis. Ibrahim, U., Petrone, GEM., Mascarenhas, J., et al.[2021]

In a study of 8 patients with acute or chronic graft versus host disease (GVHD) who were unresponsive to standard treatments, ruxolitinib demonstrated a high overall response rate of 85%, with 50% achieving complete response.

Ruxolitinib was well-tolerated, indicating it could be a promising rescue therapy for patients suffering from refractory GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis. Sarmiento Maldonado, M., Ramírez Villanueva, P., Bertín Cortes-Monroy, P., et al.[2022]

Ruxolitinib, a JAK 1/2 inhibitor, has shown benefits in treating myelofibrosis by reducing spleen size and improving symptoms, but its use around the time of hematopoietic stem cell transplantation (HCT) poses challenges such as unpredictable responses and potential cytokine storms upon discontinuation.

There is a need for more research to establish the best timing and protocols for using JAK inhibitors like ruxolitinib in HCT settings to improve patient outcomes, including engraftment and survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How we manage JAK inhibition in allogeneic transplantation for myelofibrosis. Ballinger, TJ., Savani, BN., Gupta, V., et al.[2015]

In a study of 14 patients with myelofibrosis who received allogeneic hematopoietic cell transplantation after treatment with ruxolitinib, 71.4% experienced relief from myelofibrosis-related symptoms, and 64% had a significant reduction in spleen size.

Ruxolitinib treatment prior to transplantation was associated with a high engraftment rate of 93% and may improve outcomes by reducing inflammatory cytokines, potentially lowering the risk of graft failure and acute graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib. Jaekel, N., Behre, G., Behning, A., et al.[2021]

Ruxolitinib, a JAK inhibitor, showed potential efficacy in treating a patient with refractory T-cell acute lymphoblastic leukemia (T-ALL) that had a JAK3 mutation, indicating a promising new treatment avenue for this aggressive cancer.

This case highlights the importance of using molecular markers, like JAK3 mutations, to guide treatment decisions in T-ALL, as traditional chemotherapy alone has a low cure rate of only 25-45%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib is effective in the treatment of a patient with refractory T-ALL. Jaramillo, S., Hennemann, H., Horak, P., et al.[2022]

In an expanded access program involving 609 patients (60 with acute GVHD and 549 with chronic GVHD), ruxolitinib demonstrated a tolerable safety profile, with serious adverse events (SAEs) reported in 68.3% of acute and 33.9% of chronic GVHD patients.

The most common SAEs included infections, with sepsis and respiratory failure being prevalent in acute GVHD, indicating that while ruxolitinib is generally well-tolerated, careful monitoring for infections is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety analysis of patients who received ruxolitinib for steroid-refractory acute or chronic graft-versus-host disease in an expanded access program. Schroeder, MA., Hari, PN., Blithe, A., et al.[2022]

Ruxolitinib, an oral JAK1/JAK2 inhibitor, was approved by the FDA for treating steroid-refractory acute graft-versus-host disease (GVHD) based on promising results from the Phase II REACH1 trial.

The drug shows potential not only for treating SR acute GVHD but also for preventing GVHD and possibly serving as a first-line therapy, highlighting its versatility in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of graft-versus-host disease. Ali, H., Salhotra, A., Modi, B., et al.[2021]

In a study of 159 myelofibrosis patients undergoing allogeneic stem cell transplantation, ruxolitinib pretreatment did not negatively impact key outcomes such as graft failure, engraftment, or non-relapse mortality, indicating its safety in this context.

There was a trend suggesting that patients who received ruxolitinib had a lower risk of relapse compared to those who did not, although this was not statistically significant, and overall survival rates remained similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of ruxolitinib pretreatment on outcomes after allogeneic stem cell transplantation in patients with myelofibrosis. Shahnaz Syed Abd Kadir, S., Christopeit, M., Wulf, G., et al.[2021]

In a study of 12 patients with myelofibrosis undergoing allogeneic stem cell transplantation, ruxolitinib was safely continued until stable engraftment, with no graft failures and a median leukocyte engraftment time of 12 days.

Ruxolitinib treatment led to a low incidence of acute graft-versus-host disease (GVHD) and complete chimerism in 11 patients, while also reducing inflammatory cytokine levels, indicating its potential efficacy in managing post-transplant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peritransplantation Ruxolitinib Prevents Acute Graft-versus-Host Disease in Patients with Myelofibrosis Undergoing Allogenic Stem Cell Transplantation. Kröger, N., Shahnaz Syed Abd Kadir, S., Zabelina, T., et al.[2021]

Ruxolitinib is a well-absorbed tyrosine kinase inhibitor with 95% bioavailability, primarily metabolized in the liver, and its pharmacokinetics can vary based on factors like gender and body weight.

The drug's effectiveness can be influenced by liver and renal function, necessitating dose adjustments, and while model-informed precision dosing could enhance treatment personalization, more research is needed before it can be routinely implemented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics of Ruxolitinib: A Review. Appeldoorn, TYJ., Munnink, THO., Morsink, LM., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Peritransplantation Use of Ruxolitinib in Myelofibrosis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

How we manage JAK inhibition in allogeneic transplantation for myelofibrosis. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Ruxolitinib is effective in the treatment of a patient with refractory T-ALL. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety analysis of patients who received ruxolitinib for steroid-refractory acute or chronic graft-versus-host disease in an expanded access program. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of graft-versus-host disease. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Impact of ruxolitinib pretreatment on outcomes after allogeneic stem cell transplantation in patients with myelofibrosis. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Peritransplantation Ruxolitinib Prevents Acute Graft-versus-Host Disease in Patients with Myelofibrosis Undergoing Allogenic Stem Cell Transplantation. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics of Ruxolitinib: A Review. [2023]