Peritransplant Ruxolitinib for Myelofibrosis
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Fred Hutchinson Cancer Research Center
Must be taking: JAK inhibitors
Disqualifiers: Renal impairment, Hepatic impairment, HIV, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This phase II trial studies how well administering ruxolitinib before, during, and after allogeneic hematopoietic stem cell transplantation works in preventing graft versus host disease and improving transplant outcomes in patients with primary and secondary myelofibrosis. Donor hematopoietic stem cell transplantation (HSCT) is currently the only treatment with proven curative potential for myelofibrosis, however, myelofibrosis patients have a high risk for developing graft versus host disease post-transplant. Graft versus host disease is a condition where the transplanted cells from a donor can attack the body's normal cells. Ruxolitinib, a janus-associated kinase (JAK) inhibitor, is known to decrease inflammatory signals, which may reduce spleen size and decrease symptoms such as night sweats and weight loss. Administering ruxolitinib before, during, and after transplant may decrease the incidence and severity of graft versus host disease, increase survival, and improve quality of life in patients with primary and secondary myelofibrosis.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, you must be willing to start taking ruxolitinib and continue it for a specified period around the transplant.
What data supports the effectiveness of the drug Ruxolitinib for treating myelofibrosis?
Ruxolitinib has been shown to reduce spleen size and improve symptoms in patients with myelofibrosis, even in those with low platelet counts. It has also been associated with a high rate of successful transplantation when used before stem cell transplants, although its long-term effects and optimal use around the time of transplant are still being studied.
12345Is ruxolitinib generally safe for humans?
Ruxolitinib has been studied in a large number of patients with myelofibrosis, and the most common side effects are anemia (low red blood cell count) and thrombocytopenia (low platelet count), which rarely lead to stopping the treatment. Other side effects, like infections, are usually mild. Overall, the safety profile of ruxolitinib is consistent with previous studies, and no new safety concerns have been identified.
12467How is the drug Ruxolitinib unique in treating myelofibrosis?
Ruxolitinib is unique because it is an oral medication that specifically inhibits JAK1 and JAK2 enzymes, which are involved in the development of myelofibrosis. It is particularly notable for its ability to reduce spleen size and improve symptoms, and it is being explored for use around the time of stem cell transplantation, although its effects in this context are not yet fully understood.
12348Eligibility Criteria
This trial is for adults over 18 with primary or secondary myelofibrosis, classified as intermediate-1, -2, or high-risk. Participants must have used ruxolitinib for at least 8 weeks before the transplant and be able to continue post-transplant. They should not have severe kidney or liver problems, uncontrolled infections, HIV, or be pregnant. A suitable stem cell donor is required.Inclusion Criteria
I might be a candidate for a bone marrow transplant.
I have been on ruxolitinib for at least 8 weeks and can continue it for 9 months after my transplant.
My condition is classified as intermediate-1, intermediate-2, or high-risk.
+12 more
Exclusion Criteria
I have an infection that is not under control.
Known HIV positivity
I do not have any uncontrolled infections.
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Pre-Transplant Treatment
Participants receive ruxolitinib starting 8 weeks prior to HSCT and continuing until approximately 14 days prior to conditioning regimen
8 weeks
Conditioning
Participants receive either myeloablative or reduced intensity conditioning regimens before HSCT
8 days
Transplant
Participants undergo hematopoietic stem cell transplantation (HSCT) on day 0
1 day
GVHD Prophylaxis
Participants receive ruxolitinib and other medications to prevent graft versus host disease post-transplant
9-12 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
2-5 years
Participant Groups
The study tests if ruxolitinib given before, during, and after a stem cell transplant can prevent graft versus host disease and improve outcomes in myelofibrosis patients. It involves chemotherapy drugs like Melphalan and Fludarabine followed by transplantation of donor stem cells.
1Treatment groups
Experimental Treatment
Group I: Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)Experimental Treatment15 Interventions
See detailed description.
Ruxolitinib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Jakafi for:
- Intermediate or high-risk myelofibrosis
- Polycythemia vera
- Steroid-refractory acute graft-versus-host disease
- Chronic graft-versus-host disease
- Vitiligo
🇪🇺 Approved in European Union as Jakavi for:
- Intermediate or high-risk myelofibrosis
- Polycythemia vera
- Steroid-refractory acute graft-versus-host disease
- Chronic graft-versus-host disease
- Non-segmental vitiligo
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fred Hutch/University of Washington Cancer ConsortiumSeattle, WA
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Who Is Running the Clinical Trial?
Fred Hutchinson Cancer Research CenterLead Sponsor
Fred Hutchinson Cancer CenterLead Sponsor
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.
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.
A subgroup analysis of JUMP, a phase IIIb, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis in a Brazilian cohort. [2021]Ruxolitinib has been approved for the treatment of myelofibrosis (MF). In this study, we present safety and efficacy findings from an analysis of 104 patients with intermediate- and high-risk MF in a Brazilian cohort of the JUMP study who received treatment with ruxolitinib.
Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. [2021]Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor approved for the treatment of myelofibrosis (MF). Ruxolitinib was assessed in JUMP, a large (N = 2233), phase 3b, expanded-access study in MF in countries without access to ruxolitinib outside a clinical trial, which included patients with low platelet counts (<100 × 109 /l) and patients without splenomegaly - populations that have not been extensively studied. The most common adverse events (AEs) were anaemia and thrombocytopenia, but they rarely led to discontinuation (overall, 5·4%; low-platelet cohort, 12·3%). As expected, rates of worsening thrombocytopenia were higher in the low-platelet cohort (all grades, 73·2% vs. 53·5% overall); rates of anaemia were similar (all grades, 52·9% vs. 59·5%). Non-haematologic AEs, including infections, were mainly grade 1/2. Overall, ruxolitinib led to meaningful reductions in spleen length and symptoms, including in patients with low platelet counts, and symptom improvements in patients without splenomegaly. In this trial, the largest study of ruxolitinib in patients with MF to date, the safety profile was consistent with previous reports, with no new safety concerns identified. This study confirms findings from the COMFORT studies and supports the use of ruxolitinib in patients with platelet counts of 50-100 × 109 /l. (ClinicalTrials.gov identifier NCT01493414).
Ruxolitinib before allogeneic hematopoietic transplantation in patients with myelofibrosis on behalf SFGM-TC and FIM groups. [2022]This multicenter prospective phase 2 trial analyzed disease-free survival (DFS) in myelofibrosis patients receiving ruxolitinib for 6 months before transplantation. Seventy-six patients were recruited. Age-adjusted dynamic international prognostic scoring system was intermediate-1, intermediate-2, and high in 27 (36%), 31 (41%), and 18 (24%) patients. All patients received ruxolitinib from inclusion to conditioning regimen (fludarabine-melphalan) or to progression. A donor was found in 64 patients: 18 HLA-matched sibling donor (MSD), 32 HLA-matched unrelated (UD10/10), and 14 HLA mismatched unrelated donor (UD9/10. Among 64 patients with a donor, 20 (31%) achieved a partial response before transplantation and 59 (92%) could be transplanted after ruxolitinib therapy (18/18 MSD, 30/21 UD10/10, 11/34 UD9/10), of whom 19 (32%) were splenectomized. Overall survival from inclusion was 68% at 12 months. One-year DFS after transplantation was 55%: 83%, 40%, and 34% after MSD, UD10/10 or UD9/10, respectively. Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) was 66% and non-relapse-mortality was 42% at 12 months. Short course of ruxolitinib before transplantation is followed by a high rate of transplantation. With the platform used in this protocol, outcome was much better in patients transplanted with HLA-matched sibling donor as compared to unrelated donor.
Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study. [2023]Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib-intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non-100 mg bid doses (non-100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%-57.8%). There were 41.9% (13/31) of transfusion-independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment-emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.
JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. [2022]Treatment options for myelofibrosis are limited. We evaluated the efficacy and safety of ruxolitinib, a potent and selective Janus kinase (JAK) 1 and 2 inhibitor, as compared with the best available therapy, in patients with myelofibrosis.
Janus activated kinase inhibition in myelofibrosis. [2021]Janus Activated Kinase (JAK) 2 plays an important role in the pathogenesis of myelofibrosis (MF). Ruxolitinib (INCB018424, Jakafi) is a potent dual JAK1 and JAK2 inhibitor. In November 2011, it became approved by the US FDA for the treatment of intermediate or high-risk MF. This review shall outline the role of Ruxolitinib in the current management of MF and its potential future.