Study Stopped
The study design was revised so a new protocol will be opened.
Ruxolitinib Phosphate, Tacrolimus and Sirolimus in Preventing Acute Graft-versus-Host Disease During Reduced Intensity Donor Hematopoietic Cell Transplant in Patients With Myelofibrosis
A Phase I Trial of Ruxolitinib Combined With Tacrolimus and Sirolimus as Acute Graft-versus-Host Disease (aGVHD) Prophylaxis During Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis
2 other identifiers
interventional
N/A
1 country
1
Brief Summary
This phase I trial studies the side effects and best dose of ruxolitinib phosphate when given together with tacrolimus and sirolimus in preventing acute graft-versus-host disease during reduced intensity donor hematopoietic cell transplant in patients with myelofibrosis. Sometimes transplanted cells from a donor can attack the normal tissue of the transplant patient called graft-versus-host disease. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It may also reduce graft-versus-host disease by reducing inflammation and immune modulation. Giving ruxolitinib phosphate together with tacrolimus and sirolimus after transplant may prevent graft-versus-host disease.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 18, 2015
CompletedFirst Posted
Study publicly available on registry
August 19, 2015
CompletedStudy Start
First participant enrolled
November 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2016
CompletedSeptember 14, 2016
September 1, 2016
10 months
August 18, 2015
September 12, 2016
Conditions
Outcome Measures
Primary Outcomes (3)
Incidence of adverse events recorded using the modified Bearman scale and NCI CTCAE version 4.03
Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
Up to 2 years
MTD based on dose limiting toxicity recorded using the modified Bearman scale and National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Up to 60 days post stem cell infusion
Recommended phase II dose of ruxolitinib phosphate, when given in combination with tacrolimus and sirolimus
Up to 60 days post stem cell infusion
Secondary Outcomes (9)
aGVHD graded and staged according to the Consensus grading
Up to 100 days post transplant
Changes in expression levels of biomarkers
Baseline to up to day 100
Chronic graft versus host disease evaluated and scored according to National Health Institute consensus staging
Up to 2 years
Engraftment (recovery of granulopoiesis and megakaryopoiesis)
Up to 2 years
Incidence of infection
Up to day 100 post-transplant
- +4 more secondary outcomes
Study Arms (1)
Supportive care (ruxolitinib phosphate, tacrolimus, sirolimus)
EXPERIMENTALPREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV on days -9 to -5 and melphalan IV over 20 minutes on day -4. Beginning greater than 48 hours after completion of melphalan, patients undergo peripheral blood stem cell or bone marrow transplant according to standard guidelines on day 0. GVHD PROPHYLAXIS: Patients receive ruxolitinib phosphate PO BID on days -3 to 30 tapered to day 60, tacrolimus IV continuously or PO BID on days -3 to 100 , and sirolimus PO QD on day -3 to 100. Treatment continues in the absence of disease progression or unacceptable toxicity.
Interventions
Undergo allogeneic bone marrow transplant
Undergo allogeneic hematopoeitic stem cell transplant
Given IV
Correlative studies
Given IV
Undergo hematopoietic stem cell transplant
Correlative studies
Given PO
Given PO
Given IV or PO
Eligibility Criteria
You may qualify if:
- Primary or secondary myelofibrosis intermediate or high risk by Dynamic International Prognostic Scoring System 26 (DIPSS26) in chronic or accelerated phase
- Transformed acute myeloid leukemia (AML) with marrow fibrosis is allowed, if AML is in complete remission after induction therapy
- Patients with a performance status of \>= 70% on the Karnofsky scale
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for 1 year following transplant as per City of Hope standard operating procedure, (SOP) for allogeneic transplantation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
- Bone marrow and peripheral blood studies must be available for confirmation of diagnosis; cytogenetics, flow cytometry, and molecular studies (such as JAK-2, myeloproliferative leukemia \[MPL\] and calreticulin \[CALR\] mutational status) will be obtained as per standard practice
- Bone marrow aspirates/biopsies should be performed within 23 ± 7 days from registration to confirm disease remission status
- All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical siblings who is willing to donate bone marrow or primed blood stem cells or an 8/8 allele-matched unrelated donor
- All ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques (red cell exchange or plasma exchange)
- A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm and an ejection fraction of 50% established by multi gated acquisition scan (MUGA) or echocardiogram
- Patients must have creatinine of less than or equal to 1.5 mg/dL or creatinine clearance \> 60 ml/min
- A bilirubin of up to 2.0 mg/dL, excluding patients with Gilbert's disease
- Patients should also have a serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) less than 5 times the upper limit of normal
- Pulmonary function test including diffusing capacity of the lung for carbon monoxide (DLCO) will be performed; forced expiratory volume in 1 second (FEV1) and DLCO should be greater than 50% of predicted normal value
- All subjects must have the ability to understand and the willingness to sign a written informed consent that has been approved by the City of Hope (COH) Institutional Review Board (IRB); the patient, a family member and transplant staff physician (physician, nurse, and social worker) will meet at least once prior to the subject signing consent; during this meeting all pertinent information with respect to risks and benefits to donor and recipient will be presented; alternative treatment modalities will be discussed; the risks are explained in detail in the enclosed consent form
- Prior therapy with hydroxyurea, interferon, anagrelide, ruxolitinib, hypomethylating agents, Revlimid, thalidomide, steroids, other JAK inhibitors is allowed for AML patients who are back in chronic phase MPN, prior induction chemotherapy is allowed
- +1 more criteria
You may not qualify if:
- Patients should not have any uncontrolled illness including ongoing or active infection
- Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ruxolitinib
- Patients with active 2nd malignancies other than myelofibrosis, AML, excised skin cancer, early stage cervical and prostate cancer
- Previous allogeneic hematopoietic stem cell transplantation
- Any psychiatric, social or compliance issues that, in the treating physician opinion, will interfere with completion of the transplant treatment and follow up
- Patients who have been treated with chemotherapy or radiation within two weeks of planned study enrollment; this does not include hydroxyurea or ruxolitinib, which may be continued until start of conditioning therapy
- Non-compliance defined as any subject, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
City of Hope Medical Center
Duarte, California, 91010, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Haris Ali
City of Hope Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- SUPPORTIVE CARE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 18, 2015
First Posted
August 19, 2015
Study Start
November 1, 2015
Primary Completion
September 1, 2016
Last Updated
September 14, 2016
Record last verified: 2016-09