Ruxolitinib Phosphate, Tacrolimus and Sirolimus in Preventing Acute Graft-versus-Host Disease During Reduced Intensity Donor Hematopoietic Cell Transplant in Patients With Myelofibrosis
NCT ID: NCT02528877
Last Updated: 2016-09-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
WITHDRAWN
PHASE1
INTERVENTIONAL
2015-11-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Ruxolitinib Phosphate and Chemotherapy Given Before and After Reduced Intensity Donor Stem Cell Transplant in Treating Patients With Myelofibrosis
NCT02917096
Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer
NCT00589563
Ruxolitinib With Tacrolimus and Methotrexate for the Prevention of Graft Versus Host Disease in Pediatric and Young Adult Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome
NCT06128070
Ruxolitinib Before, During and After Hematopoietic Cell Transplant in Older Patients With Myelofibrosis and Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes
NCT07228624
Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplant
NCT00691015
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. Among the dose levels tested, to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of ruxolitinib (ruxolitinib phosphate), when given in combination with tacrolimus and sirolimus (TAC/SIR) as acute graft-versus-host disease (aGVHD) prophylaxis as part of reduced intensity allogeneic hematopoietic cell transplant (HCT), in patients with myelofibrosis or other related myeloid neoplasm with marrow fibrosis.
SECONDARY OBJECTIVES:
I. To determine if the addition of ruxolitinib, to the standard aGVHD prophylactic regimen of TAC/SIR, is safe by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.
II. To estimate the cumulative incidence of aGVHD and non-relapse mortality (NRM) at 100-days post transplant.
III. To estimate the cumulative incidence of chronic GVHD at 1- and 2-years post transplant.
IV. To characterize and evaluate hematologic recovery, donor cell engraftment and immune reconstitution by cell count and flow cytometry of lymphocyte subsets.
V. To estimate the probabilities of overall and progression-free survival (OS/PFS) at 1- and 2-years post transplant.
VI. To characterize changes in aGVHD biomarkers (regenerating islet-derived 3-alpha \[Reg-3alpha\], soluble tumor necrosis factor receptor I \[sTNF RI\], interleukin 2 receptor alpha \[IL2Ralpha\]), Janus-associated kinase (JAK)-regulated pro-inflammatory cytokines (i.e. interleukin \[IL\]-6, tumor necrosis factor \[TNF\] alpha, C-reactive protein \[CRP\], beta 2 microglobulin) and signal transducer and activator of transcription 3 (STAT3) phosphorylation (downstream of JAK signaling) over time and by aGVHD status/grade.
OUTLINE: This is a dose-escalation study of ruxolitinib phosphate.
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (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 orally (PO) twice daily (BID) on days -3 to 30 tapered to day 60, tacrolimus IV continuously or PO BID on days -3 to 100 , and sirolimus PO once daily (QD) on day -3 to 100. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up 2 years.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
SUPPORTIVE_CARE
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Supportive care (ruxolitinib phosphate, tacrolimus, sirolimus)
PREPARATIVE 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.
Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplant
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic hematopoeitic stem cell transplant
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative studies
Melphalan
Given IV
Peripheral Blood Stem Cell Transplantation
Undergo hematopoietic stem cell transplant
Pharmacological Study
Correlative studies
Ruxolitinib Phosphate
Given PO
Sirolimus
Given PO
Tacrolimus
Given IV or PO
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplant
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic hematopoeitic stem cell transplant
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative studies
Melphalan
Given IV
Peripheral Blood Stem Cell Transplantation
Undergo hematopoietic stem cell transplant
Pharmacological Study
Correlative studies
Ruxolitinib Phosphate
Given PO
Sirolimus
Given PO
Tacrolimus
Given IV or PO
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* DONOR: Donor evaluation and eligibility will be assessed as per current City of Hope SOP
Exclusion Criteria
* 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
18 Years
75 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
City of Hope Medical Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Haris Ali
Role: PRINCIPAL_INVESTIGATOR
City of Hope Medical Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
City of Hope Medical Center
Duarte, California, United States
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2015-01333
Identifier Type: REGISTRY
Identifier Source: secondary_id
14129
Identifier Type: OTHER
Identifier Source: secondary_id
14129
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.