Ruxolitinib + Allogeneic Stem Cell Transplantation in AML

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03286530

Collaborator

Washington University School of Medicine (Other), Vanderbilt University (Other), Ohio State University (Other)

Enrollment

Locations

Arm

81.9

Anticipated Duration (Months)

10.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Acute Myeloid Leukemia in Remission Allogeneic Stem Cell Transplantation	Drug: Ruxolitinib	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Nov 3, 2017

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

1-year GVHD/relapse free survival rate (GRFS rate) [1 Year]
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 [Until disease progression or death from any cause, approximately 5 years]
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 [Until death, approximately 5 years]
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 [2 Years]
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 [2 Years]
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) [2 Years]
The amount of time between receiving the HSCT and death due to a treatment related cause. Time to relapse is considered a competing risk.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02115
3	Washington University	Saint Louis	Missouri	United States	63130
4	The Ohio State University	Columbus	Ohio	United States	43210
5	Vanderbilt University	Nashville	Tennessee	United States	37235
6	Medical College of Wisconsin	Wauwatosa	Wisconsin	United States	53226