Ruxolitinib + Allogeneic Stem Cell Transplantation in AML

Phase II Study of Maintenance Ruxolitinib After Allogeneic Stem Cell Transplantation for Older Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) in Complete Remission

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

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Allogeneic Stem Cell Transplantation; Acute Myeloid Leukemia in Remission
• Intervention / Treatment: Drug: Ruxolitinib

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved ruxolitinib for this specific disease but it has been approved for other blood diseases.

In this research study, investigators are trying to discover if ruxolitinib will decrease chances of relapse after having an allogeneic stem cell transplantation.

Ruxolitinib is a medication that blocks certain proteins called tyrosine kinases. Specifically, it blocks tyrosine kinases called JAK2. Many cancers have over active "cell signaling." What this means is that certain functions in the cancer cells never turn off and this makes them grow in an uncontrolled way. Ruxolitinib, shuts down the pathway that depends on the JAK2 tyrosine kinases. The JAK2 pathway is over active with acute myeloid leukemia. Ruxolitinib has also been shown to lower the rates of graft versus host disease, a complication of transplant. The exact way ruxolitinib does this is not yet clear but it may have to do with its ability to block the JAK2 pathway since this pathway can also lead to inflammation in the body.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gabriella Hobbs, MD; Phone Number: 617-726-8747; Email: Ghobbs@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Gabriella Hobbs, MD; Phone Number: 617-726-8748
      • Principal Investigator: Gabriella Hobbs, MD
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Ajoy Dias, MD; Phone Number: 617-667-9920
      • Principal Investigator: Ajoy Dias, MD
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Recruiting
      • Washington University
      • Contact: Mark Schroeder, MD; Email: markschroeder@wustl.edu
      • Principal Investigator: Mark Schroeder, MD
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University
      • Contact: Sumithira Vasu, MBBS; Email: Sumithira.Vasu@osumc.edu
      • Principal Investigator: Sumithira Vasu, MBBS
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Recruiting
      • Vanderbilt University
      • Principal Investigator: Bhagirathbhai Dholaria, MD
      • Contact: Bhagirathbhai Dholaria, MD; Email: Bhagirathbhai.r.dholaria@vumc.org
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin
      • Contact: Sameem Abedin, MD; Email: sabedin@mcw.edu
      • Principal Investigator: Sameem Abedin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have pathologically confirmed AML in CR1 as defined by:

  • Bone marrow biopsy with < 5% blasts
  • No clusters or collections of blast cells
  • No extramedullary leukemia
  • Absolute neutrophil count ≥ 1000/µL (achieved post-induction at some point)

  • Please note that full platelet recovery is not necessary, and thus, patients achieving CRp are eligible.

    ---Or participants have pathologically confirmed MDS as defined by:

  • Bone marrow biopsy with <10% blasts
  • Patients receiving MDS-directed therapy must be off treatment for > 2 weeks prior to start of conditioning.

• Participants must be designated to undergo reduced intensity allogeneic peripheral blood hematopoietic stem cell transplantation (HCT). Consent will be obtained prior to admission for HCT. The following HCT 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 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/m2 IV total dose and melphalan is 100-140 mg/m2 IV total dose. Exact logistics of administration are at the discretion of institutional standard.
    • Fludarabine / Busulfan where fludarabine is ≥ 90 mg/m2 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/m2 IV total dose and busulfan is dosed to achieve AUC of 4000 µmol/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 HCT and methotrexate given after HCT on days +1, +3 and +6 ± +11 at a dose of 5-10 mg/m2 IV. Exact logistics are at the discretion of the treating institution.
• Age ≥ 60 and ≤ 80 years old
• 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

Exclusion Criteria:

• Have had a prior allogeneic HSCT.

• Patients without normal organ function defined as follows:

  • AST (SGOT), ALT (SGPT) and Alkaline Phosphatase >3 × institutional Upper Limit of Normal (ULN)
  • Direct 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 (LVEF < 40%, as measured by MUGA scan or echocardiogram)
• Have an uncontrolled intercurrent illness including, but not limited to, ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• 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.
• Be HIV-positive
• Have a systemic infection requiring IV antibiotic therapy, nor any other severe 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ruxolitinib; 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.	Drug: Ruxolitinib; Patients who fulfill eligibility criteria will be entered into the trial to receive Ruxolitinib. After the screening procedures confirm participation in the research study. The participant will be given a drug diary. The participant will be asked to document information in the drug diary about the study treatment.; Other Names: Jakafi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year GVHD/relapse free survival rate (GRFS rate)	The number of participants surviving after one year that have not experienced graft-versus-host disease (GVHD) or graft relapse (GRFS rate).	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Kaplan-Meier estimates of progression free survival (PFS) will be calculated, with patients without an event being censored at last date of contact	Until disease progression or death from any cause, approximately 5 years
Overall Survival	Overall survival is measured as the time from the hematopoietic stem cell transplantation (HSCT) until death. Participants without an event will be censored at the date of last contact.	Until death, approximately 5 years
Cumulative incidence of drug related toxicities	Cumulative incidence of treatment related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE 4). Early deaths from all other causes are considered a competing risk.	2 Years
Time to Relapse	The amount of time from the hematopoietic stem cell transplantation (HSCT) until disease relapse. Relapse is the recurrence of cancer after having a bone marrow biopsy without evidence of cancer. Time to treatment-related mortality is considered a competing risk.	2 Years
Time to treatment-related mortality (TRM)	The amount of time between receiving the HSCT and death due to a treatment related cause. Time to relapse is considered a competing risk.	2 Years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Washington University School of Medicine; Medical College of Wisconsin; Vanderbilt University; Ohio State University
• Investigators: Principal Investigator: Gabriell Hobbs, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2017
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 9, 2017
• First Submitted That Met QC Criteria: September 15, 2017
• First Posted (Actual): September 18, 2017

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Acute Myeloid Leukemia in Remission; Allogenic Stem Cell Transplantation
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 17-273

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No