Ruxolitinib + Stem Cell Transplant for Acute Myeloid Leukemia
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Massachusetts General Hospital
Must not be taking: Antibiotics, Antifungals, Antivirals
Disqualifiers: Prior HSCT, Organ dysfunction, Heart failure, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
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
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.
12345Is 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.
12678How 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.
128910Eligibility 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.
+4 more
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.
+8 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: RuxolitinibExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The Ohio State UniversityColumbus, OH
Massachusetts General HospitalBoston, MA
Washington UniversitySaint Louis, MO
Medical College of WisconsinWauwatosa, WI
More Trial Locations
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
Washington University School of MedicineCollaborator
Vanderbilt UniversityCollaborator
Ohio State UniversityCollaborator
Medical College of WisconsinCollaborator
References
Peritransplantation Use of Ruxolitinib in Myelofibrosis. [2021]Ruxolitinib is an oral JAK1/2 inhibitor that is approved for use in patients with intermediate and high-risk myelofibrosis (MF) based on its proven spleen and symptom burden reduction. Its impact on hematopoietic stem cell transplantation (HSCT) outcomes is largely unknown, however. A significant number of patients proceeding to HSCT have been treated with ruxolitinib, and the specifics of its peritransplantation use vary widely in the published literature. Here we review the currently published data and experience to guide management of patients with MF on ruxolitinib proceeding to HSCT.
Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis. [2022]Ruxolitinib is a potent inhibitor of JAK1/2 with proven efficacy in myelofibrosis. In recent years, research in graft versus host disease (GVHD) has revealed the role of activation of JAK pathways in alloreactive lymphocytes. Some reports have shown significant responses in refractory GVHD patients.
How we manage JAK inhibition in allogeneic transplantation for myelofibrosis. [2015]Hematopoietic stem cell transplantation (HCT) is currently the only curative treatment for myelofibrosis (MF), but this option is complicated by high incidences of associated morbidity and mortality. Ruxolitinib, a janus-activated kinase (JAK) 1/2 inhibitor, has proven to be beneficial in reduction of splenomegaly, improvement of constitutional symptoms, and possibly in overall survival. However, use of JAK inhibitors in the peritransplant period has been complicated by unpredictable response, return of MF symptoms or cytokine storm reaction upon discontinuation, and lack of long-term response data. This review considers the current limited available data on JAK inhibitor use prior to HCT, including common side effects and possible impact of severe adverse events on discontinuation of the drug. We provide our experience and recommendations regarding use of JAK inhibition in patients undergoing HCT. Additional studies are needed to determine the optimal schedule of JAK inhibitors in the transplant protocols and their impact on engraftment, graft-versus-host disease, and survival.
Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib. [2021]The Janus-activated kinase 1 (JAK1) and JAK2 inhibitor ruxolitinib is effective in decreasing symptomatic splenomegaly and myelofibrosis (MF)-related symptoms. However, allogeneic hematopoietic cell transplantation (HCT) remains the only curative option. We evaluated the impact of ruxolitinib on the outcome after HCT. A cohort of 14 patients (median age 58 years) received a subsequent graft from related (n=3) and unrelated (n=11) donors after a median exposure of 6.5 months to ruxolitinib. At HCT, MF risk for survival according to the International Prognostic Scoring System was intermediate-2 or high risk in 86% of patients. Under ruxolitinib, MF-related symptoms were ameliorated in 10 (71.4%) patients and the palpable spleen reduced by a median of 41% in 7 (64%) of 11 patients with splenomegaly. Engraftment occurred in 13 (93%) patients. Acute GvHD grade-III occurred in 2 (14%) patients. Median follow-up was 9 months. Survival, EFS and treatment-related mortality were 78.6, 64 and 7%, respectively. Through the anti-JAK-mediated reduction in both cytokines and splenomegaly as well as improvement in performance status, ruxolitinib might improve outcome after allogeneic HCT in patients with MF. The downregulation of inflammatory cytokines might have a beneficial impact on graft failure and acute GvHD.
Ruxolitinib is effective in the treatment of a patient with refractory T-ALL. [2022]T-cell acute lymphoblastic leukemia (T-ALL) is a rare, aggressive T-cell malignancy. Chemotherapy alone cures only 25-45% of the cases, thus, novel treatment agents and strategies are urgently needed. We assessed the efficacy of ruxolitinib in a patient with a cutaneous relapse after allogeneic blood cell transplantation of a refractory T-ALL with a Janus kinase 3 (JAK3) mutation. In this case report, we were able to show the potential benefit of the JAK inhibitor ruxolitinib in JAK3-mutated refractory T-ALL and emphasize the importance of integrating molecular markers in current treatment decision making for patients with T-ALL.
Safety analysis of patients who received ruxolitinib for steroid-refractory acute or chronic graft-versus-host disease in an expanded access program. [2022]Outside of clinical trials and before commercial availability for acute and chronic graft-versus-host disease (GVHD), the Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was available to US patients with steroid-refractory GVHD through an open-label, multicenter expanded access program (EAP) sponsored by Incyte Corporation. To assess the safety of ruxolitinib, data on serious adverse events (SAEs) reported among patients in the EAP were collected. Patients ≥12 years old who received allogeneic hematopoietic cell transplantation for a hematologic malignancy and developed any-grade acute or chronic steroid-refractory GVHD received ruxolitinib at a starting dose of 5 mg twice daily (BID; acute GVHD) or 10 mg BID (chronic GVHD). At data extraction (May 8, 2020), 60 patients with acute GVHD and 549 with chronic GVHD were enrolled. In the acute and chronic GVHD cohorts, 41 (68.3%) and 186 (33.9%) patients, respectively, had ≥1 SAE. Sepsis (8.3%) and respiratory failure (6.7%) were the most common SAEs in the acute GVHD cohort, and pneumonia (4.9%), sepsis (3.8%), and lung infection (3.5%) in chronic GVHD. Infection SAEs were reported in 23.3% and 20.0% of patients with acute and chronic GVHD, respectively. Overall, these safety findings demonstrate the tolerability of ruxolitinib in steroid-refractory GVHD.
Ruxolitinib for the treatment of graft-versus-host disease. [2021]Introduction: Ruxolitinib is an oral selective JAK1/JAK2 inhibitor, initially approved by the FDA for the treatment of intermediate-2 or high-risk myelofibrosis and patients with polycythemia vera who have had an inadequate response or are intolerant to hydroxyurea.Areas covered: Accumulating evidence supports the role of JAK1/JAK2 pathways in the pathogenesis of graft-versus-host disease (GVHD), and preclinical studies have demonstrated promising efficacy of ruxolitinib in treatment/prevention of GVHD. Early clinical observations that ruxolitinib was effective in treatment of steroid-refractory (SR) acute and chronic GVHD led to the development of prospective clinical trials; Phase II REACH1 (NCT02953678), Phase III REACH2 (NCT02913261), and REACH3 (NCT03112603). Based on the data from the REACH1 trial, ruxolitinib was approved by the FDA in May 2019 for SR acute GVHD in adult and pediatric patients 12 years and older.Expert opinion: Ruxolitinib and other JAK1/JAK2 inhibitors hold promise in other treatment settings such as GVHD prevention and/or first-line therapy.
Impact of ruxolitinib pretreatment on outcomes after allogeneic stem cell transplantation in patients with myelofibrosis. [2021]Ruxolitinib is the first approved drug for treatment of myelofibrosis, but its impact of outcome after allogeneic stem cell transplantation (ASCT) is unknown.
Peritransplantation Ruxolitinib Prevents Acute Graft-versus-Host Disease in Patients with Myelofibrosis Undergoing Allogenic Stem Cell Transplantation. [2021]JAK inhibition by ruxolitinib is approved for treating myelofibrosis and also has shown efficacy in treating steroid-resistant acute and chronic graft-versus-host disease (GVHD). In 12 patients with myelofibrosis (median age, 63 years; range, 43 to 71 years) who were treated with ruxolitinib and underwent allogeneic stem cell transplantation (ASCT), ruxolitinib was continued (2 × 5 mg daily) until stable engraftment. No graft failure was observed, and leukocyte engraftment was achieved after a median of 12 days (range, 11 to 18 days). One patient developed fever of unknown origin after discontinuation of ruxolitinib; otherwise, no withdrawal syndrome was observed. Overall, only 1 patient each experienced acute GVHD grade I or II, resulting in an 8% incidence of acute GVHD grade II-IV at day +100, with no nonrelapse mortality. Complete chimerism was achieved in 11 patients after a median of 40 days, and molecular clearance of the underlying driver mutation was noted in 10 patients after a median of 32 days. Cytomegalovirus (CMV) reactivation occurred in 5 patients (41%), 1 of whom had CMV colitis as well, but all resolved after ganciclovir treatment. In 2 patients, ruxolitinib had to be discontinued on day 17 and day 18 after ASCT due to cytopenia after engraftment. Levels of inflammatory cytokines IL-8, IL-10, IL-6, TNFR2, INF-α, and INF-β were reduced after ruxolitinib treatment. After day +100, 4 patients developed acute GVHD (1 with grade I, 2 with grade II, and 1 with grade III) after tapering of cyclosporine, and all patients were alive at a median follow-up of 17 months (range, 12 to 18 months).
Pharmacokinetics and Pharmacodynamics of Ruxolitinib: A Review. [2023]Ruxolitinib is a tyrosine kinase inhibitor targeting the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways. Ruxolitinib is used to treat myelofibrosis, polycythemia vera and steroid-refractory graft-versus-host disease in the setting of allogeneic stem-cell transplantation. This review describes the pharmacokinetics and pharmacodynamics of ruxolitinib.