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Ruxolitinib Before, During and After Hematopoietic Cell Transplant in Older Patients With Myelofibrosis and Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes

ConditionsMyelodysplastic/Myeloproliferative NeoplasmPrimary MyelofibrosisSecondary Myelofibrosis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorFred Hutchinson Cancer Center

About this trial

This phase II trial tests the effect of adding ruxolitinib to standard graft versus host disease (GVHD) prevention in treating older patients with myelofibrosis (MF) or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes before, during, and after a donor (allogeneic) hematopoietic cell transplant (HCT). Allogeneic HCT is a procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical donor. Giving chemotherapy, such as cytoxan and busulfan or fludarabine and melphalan, before a donor transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. However, sometimes the transplanted cells from a donor can attack the body's normal cells (called GVHD). Giving standard prevention (prophylaxis) therapies, such as tacrolimus and methotrexate, after the transplant may stop this from happening. Methotrexate, a type of antifolate, is in a class of medications called antimetabolites. Methotrexate stops cells from using folic acid to make deoxyribonucleic acid and may kill cancer cells. Tacrolimus is used to help reduce the risk of rejection by the body of organ and bone marrow transplants. Ruxolitinib, a type of Janus-associated kinase (JAK) inhibitor, blocks a protein called JAK, which may help keep abnormal blood cells or cancer cells from growing. It may also lower the body's immune response and prevent the development of GVHD. Giving ruxolitinib before, during and after allogeneic HCT in addition to standard GVHD prophylaxis may be safe, tolerable and effective in preventing GVHD and improving outcomes in older patients with MF or MDS/MPN overlap syndrome.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

PART 1 JAK INHIBITOR ADMINISTRATION: Age 18-75 years

Patients > 75 must be considered an HCT candidate, meet all protocol criteria and have comorbidity score =< 3 and Karnofsky performance status (KPS) > or = to 90. Patients. > 75 who do not meet these criteria may be presented at PCC for consensus exception

PART 1 JAK INHIBITOR ADMINISTRATION: Disease criteria

Diagnosis of primary or secondary MF as defined by the 2022 World Health Organization classification system or the International Consensus Classification for Myeloid and Acute Leukemias

Disqualifiers

PART 1 JAK INHIBITOR ADMINISTRATION: Contraindication to receiving ruxolitinib including patients who have known hypersensitivity to JAK inhibitors and excipients

PART 1 JAK INHIBITOR ADMINISTRATION: History of prior allogeneic transplant

PART 1 JAK INHIBITOR ADMINISTRATION: Leukemic transformation (> 20% blasts)

PART 1 JAK INHIBITOR ADMINISTRATION: Uncontrolled viral, bacterial, or fungal infection despite being on therapy

Trial design

Design model

Single group

Treatments tested in this trial

  • Ruxolitinib

    Drug

    Given PO

  • Allogeneic Hematopoietic Stem Cell Transplantation

    Procedure/Surgery

    Given infusion

  • Busulfan

    Drug

    Given IV

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Cyclophosphamide

    Drug

    Given IV

  • Echocardiography Test

    Procedure/Surgery

    Undergo echocardiography

  • Fludarabine

    Drug

    Given IV

  • JAK Inhibitor

    Drug

    Given JAK inhibitor

  • Melphalan

    Drug

    Given IV

  • Methotrexate

    Drug

    Given IV

  • Tacrolimus

    Drug

    Given IV or PO

  • Biospecimen Collection

    Procedure/Surgery

    Undergo urine and blood sample collection

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow biopsy and aspiration

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy and aspiration

Treatment groups

50 Participants
are divided into 1 treatment group
Group A: Treatment (ruxolitinib)Experimental treatment 14 interventions

Trial outcomes

Primary outcomes

1

Incidence of grade II-IV graft versus host disease (GVHD) requiring systemic immune suppression

Will be estimated as a simple proportion, and the upper bound of the one-sided 95% confidence interval for the estimated proportion will be estimated using the Clopper-Pearson method. The exact binomial test will be used to compare the observed probability to the benchmark of 65%.

Time frame
Up to day-100

Secondary outcomes

1

Incidence of grade III-IV acute GVHD

Will be estimated as simple proportions and informally compared to the results from the historical cohort.

Time frame
Up to day-100
2

Incidence of any-grade chronic GVHD

Will be treated as time-to-event endpoints, with specified point estimates.

Time frame
Up to 1 and 2 years
3

Incidence of moderate-to-severe chronic GVHD

Will be treated as time-to-event endpoints, with specified point estimates.

Time frame
Up to 1 and 2 years
4

Non-relapse mortality (NRM)

Will be estimated as simple proportions and informally compared to the results from the historical cohort.

Time frame
At day-100

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fred Hutchinson Cancer Center

Lead sponsor

Incyte Corporation

Collaborator

Source ClinicalTrials.gov
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