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Ruxolitinib + Allogeneic Stem Cell Transplantation in AML

Primary Purpose

Acute Myeloid Leukemia, Acute Myeloid Leukemia in Remission, Allogeneic Stem Cell Transplantation

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ruxolitinib
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Acute Myeloid Leukemia in Remission, Allogenic Stem Cell Transplantation

Eligibility Criteria

60 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.
  • 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:

    • Platelet count of ≤50,000/ μL, hemoglobin of ≤8g/dL, or ANC of ≤1000 AST (SGOT), ALT (SGPT) and Alkaline Phosphatase ≥5 × 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 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 HIV-positive and on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with ruxolitinib. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy.
  • 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

Sites / Locations

  • Beth Israel Deaconess Medical CenterRecruiting
  • Massachusetts General HospitalRecruiting
  • Washington UniversityRecruiting
  • The Ohio State UniversityRecruiting
  • Vanderbilt UniversityRecruiting
  • Medical College of WisconsinRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ruxolitinib

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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
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.
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.
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.
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.

Full Information

First Posted
August 9, 2017
Last Updated
March 24, 2023
Sponsor
Massachusetts General Hospital
Collaborators
Washington University School of Medicine, Vanderbilt University, Ohio State University, Medical College of Wisconsin
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1. Study Identification

Unique Protocol Identification Number
NCT03286530
Brief Title
Ruxolitinib + Allogeneic Stem Cell Transplantation in AML
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 3, 2017 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Washington University School of Medicine, Vanderbilt University, Ohio State University, Medical College of Wisconsin

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Myeloid Leukemia in Remission, Allogeneic Stem Cell Transplantation
Keywords
Acute Myeloid Leukemia, Acute Myeloid Leukemia in Remission, Allogenic Stem Cell Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
64 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ruxolitinib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
Jakafi
Intervention Description
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.
Primary Outcome Measure Information:
Title
1-year GVHD/relapse free survival rate (GRFS rate)
Description
The number of participants surviving after one year that have not experienced graft-versus-host disease (GVHD) or graft relapse (GRFS rate).
Time Frame
1 Year
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
Kaplan-Meier estimates of progression free survival (PFS) will be calculated, with patients without an event being censored at last date of contact
Time Frame
Until disease progression or death from any cause, approximately 5 years
Title
Overall Survival
Description
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.
Time Frame
Until death, approximately 5 years
Title
Cumulative incidence of drug related toxicities
Description
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.
Time Frame
2 Years
Title
Time to Relapse
Description
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.
Time Frame
2 Years
Title
Time to treatment-related mortality (TRM)
Description
The amount of time between receiving the HSCT and death due to a treatment related cause. Time to relapse is considered a competing risk.
Time Frame
2 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gabriella Hobbs, MD
Phone
617-726-8747
Email
Ghobbs@mgh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gabriell Hobbs, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ajoy Dias, MD
Phone
617-667-9920
First Name & Middle Initial & Last Name & Degree
Ajoy Dias, MD
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabriella Hobbs, MD
Phone
617-726-8748
First Name & Middle Initial & Last Name & Degree
Gabriella Hobbs, MD
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mark Schroeder, MD
Email
markschroeder@wustl.edu
First Name & Middle Initial & Last Name & Degree
Mark Schroeder, MD
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sumithira Vasu, MBBS
Email
Sumithira.Vasu@osumc.edu
First Name & Middle Initial & Last Name & Degree
Sumithira Vasu, MBBS
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37235
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bhagirathbhai Dholaria, MD
Email
Bhagirathbhai.r.dholaria@vumc.org
First Name & Middle Initial & Last Name & Degree
Bhagirathbhai Dholaria, MD
Facility Name
Medical College of Wisconsin
City
Wauwatosa
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sameem Abedin, MD
Email
sabedin@mcw.edu
First Name & Middle Initial & Last Name & Degree
Sameem Abedin, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Ruxolitinib + Allogeneic Stem Cell Transplantation in AML

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