Clinical Trials /

Ruxolitinib + Allogeneic Stem Cell Transplantation in AML

NCT03286530

Description:

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

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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) in First Complete Remission (CR1)

Clinical Trial IDs

  • ORG STUDY ID: 17-273
  • NCT ID: NCT03286530

Conditions

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

Interventions

DrugSynonymsArms
RuxolitinibJakafiRuxolitinib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
RuxolitinibExperimentalFollowing 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.
  • Ruxolitinib

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.

          -  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
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:1-year GVHD/relapse free survival rate (GRFS rate)
Time Frame:1 Year
Safety Issue:
Description: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

Measure:Progression Free Survival
Time Frame:Until disease progression or death from any cause, approximately 5 years
Safety Issue:
Description:Kaplan-Meier estimates of progression free survival (PFS) will be calculated, with patients without an event being censored at last date of contact
Measure:Overall Survival
Time Frame:Until death, approximately 5 years
Safety Issue:
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.
Measure:Cumulative incidence of drug related toxicities
Time Frame:2 Years
Safety Issue:
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.
Measure:Time to Relapse
Time Frame:2 Years
Safety Issue:
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.
Measure:Time to treatment-related mortality (TRM)
Time Frame:2 Years
Safety Issue:
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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Acute Myeloid Leukemia
  • Acute Myeloid Leukemia in Remission
  • Allogenic Stem Cell Transplantation

Last Updated

July 9, 2019