Ruxolitinib Phosphate in Treating Older Patients with Acute Myeloid Leukemia in First Complete Remission after Donor Stem Cell Transplant
This phase II trial studies how well ruxolitinib phosphate works in treating older patients with acute myeloid leukemia in first complete remission after donor stem cell transplant. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
- Participants must have pathologically confirmed acute myeloid leukemia (AML) in first complete remission (CR1) as defined by: * Bone marrow biopsy with < 5% blasts * No clusters or collections of blast cells * No extramedullary leukemia * Absolute neutrophil count >= 1000/uL (achieved post-induction at some point) * Please note that full platelet recovery is not necessary, and thus, patients achieving pathological complete remission (CRp) are eligible
- Participants must be designated to undergo reduced intensity allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT); consent will be obtained prior to admission for HSCT; the following HSCT conditions must be planned: * Donors must be 8/8 HLA-matched (at the allele level) as defined by matching at HLA-A, -B, -DR and –C who pass institutional standard to serve as a peripheral blood stem cell donor * Donor grafts must be granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells with dose and apheresis logistics at the discretion of institutional standard * Conditioning therapy will be one of the following 3 options: ** Fludarabine/melphalan where fludarabine is >= 90 mg/m^2 intravenously (IV) total dose and melphalan is 100-140 mg/m^2 IV total dose; exact logistics of administration are at the discretion of institutional standard ** Fludarabine/busulfan where fludarabine is >= 90 mg/m^2 IV total dose and busulfan = 6.4 mg/kg IV total dose; exact logistics of administration are at the discretion of institutional standard ** Fludarabine/busulfan where fludarabine is >= 90 mg/m^2 IV total dose and busulfan is dosed to achieve area under the curve (AUC) of 4000 umol/min based on a pharmacokinetics determined from a test dose; exact logistics are at the discretion of institutional standard * GVHD prophylaxis is comprised of tacrolimus/short course methotrexate as defined by tacrolimus started prior to day 0 of HSCT and methotrexate given after HSCT on days +1, +3 and +6 +/- +11 at a dose of 5-10 mg/m^2 IV; exact logistics are at the discretion of the treating institution
- Eastern Cooperative Oncology Group (ECOG) performance status 0–2
- Male participants must agree to use an acceptable method for contraception during the entire study treatment period and through 6 months after the last dose of treatment
- Ability to understand and the willingness to sign a written informed consent document
- Have had a prior allogeneic HSCT
- Platelet count of =< 50,000/uL
- Hemoglobin of =< 8 g/dL or
- Absolute neutrophil count (ANC) of < 1000
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and alkaline phosphatase >= 3 x institutional upper limit of normal (ULN)
- Total bilirubin > 2.0 mg/dL
- Adequate renal function as defined by calculated creatinine clearance =< 40 mL/min (Cockcroft-Gault formula)
- Have a history of other malignancy(ies) unless: They have been disease-free for at least 5 years and are deemed by the treating investigator to be at low risk for recurrence of that malignancy, or the only cancer they have had is cervical cancer in situ, or basal cell or squamous cell carcinoma of the skin
- Have a chronic or active infection that requires systemic antibiotics, antifungal or antiviral treatment
- Have current or a history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (left ventricular ejection fraction [LVEF] < 40%, as measured by multigated acquisition [MUGA] scan or echocardiogram)
- Have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Be human immunodeficiency virus (HIV)-positive
- Have active uncontrolled infection; an active uncontrolled infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection; persisting fever without signs or symptoms will not be interpreted as an active uncontrolled infection
- Planned use of ex vivo or in vivo T-cell depletion
- Have current or a history of ventricular or life-threatening arrhythmias or diagnosis
Locations & Contacts
Contact: Myrna Rita Nahas
Contact: Gabriela Soriano Hobbs
Contact: Mark Andrew Schroeder
Contact: Sumithira Vasu
Contact: Michael T. Byrne
Contact: Sameem M. Abedin
Trial Objectives and Outline
I. To evaluate the 1 year graft versus host disease (GVHD)/relapse free survival rate (graft-versus-host disease-free, relapse-free survival [GRFS] rate) from date of hematopoietic stem cell transplantation (HSCT).
I. To evaluate progression-free survival (PFS) and overall survival (OS) from date of HSCT.
II. To detect and categorize, according to severity, the cumulative incidences of drug-related toxicities (both hematologic and non-hematologic).
III. To evaluate disease relapse and treatment related mortality.
IV. To determine the cumulative incidence of acute GVHD after HSCT.
V. To determine the cumulative incidence of chronic GVHD after HSCT.
Between 30-100 days after completion standard of care HSCT, patients receive ruxolitinib phosphate orally (PO) twice daily (BID). Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.
Trial Phase & Type
Dana-Farber Harvard Cancer Center
Gabriela Soriano Hobbs
Secondary IDs NCI-2017-02343
Clinicaltrials.gov ID NCT03286530