Acute Lymphoblastic LeukemiaPhase 2NCT06128070
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
A Phase 2 study testing Biospecimen Collection, Chest Computed Tomography and Echocardiography in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by City of Hope Medical Center at 1 site in United States.
Trial summary
This phase II trial tests how well ruxolitinib with tacrolimus and methotrexate work to prevent the development 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. Read more about this study
- Who is it for?
- Ages 2 to 22 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndrome
- What is being tested?
- Biospecimen Collection, Chest Computed Tomography and Echocardiography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2024to 22 Nov 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Documented informed consent of the participant and/or legally authorized representative
- Assent, when appropriate, will be obtained per institutional guidelines
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- If unavailable, exceptions may be granted with study primary investigator (PI) approval
- Age: 2-22
- Weight ≥25kg
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- Eastern Cooperative Oncology Group (ECOG) ≤ 2
- Performance status: Karnofsky ≥ 60% for patients ≥ 16 years old OR Lansky status ≥ 60% for patients < 16 years old
- Candidate for allogeneic bone marrow transplant with and available matched related donor (MRD) or an 8/8 matched unrelated donor (MUD) who is willing to donate bone marrow (BM) or mobilized peripheral blood stem cells
- Note: Donor selection process will be in accordance with City of Hope (COH)-standard operating procedures (SOPs) (B.001.09 Allogeneic Cellular Therapy Product Donor Evaluation, Selection \& Consent), which follows Food and Drug Administration (FDA) guidelines for donation of hematopoietic stem/progenitor cells (HPCs) obtained from peripheral blood or bone marrow
- Diagnosis of acute leukemia (acute myeloid leukemia [AML] or acute lymphoblastic leukemia [ALL]) in complete remission, or myelodysplastic syndrome (MDS)
- Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 from prior anti-cancer therapy
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (to be performed within 30 days prior to day 1 of protocol therapy)
- Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
Who cannot join
- Autologous stem cell transplant within 1 year prior to day 1 of protocol therapy
- Prior allogeneic transplantation
- Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 days prior to day 1 of protocol therapy
- Note: Conditioning regimen within 21 days prior to day 1 of protocol therapy is not considered as an exclusion criterion.
- Note: Patients on maintenance chemotherapy with agents listed are not excluded
- Herbal medications
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- History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
- History of active tuberculosis
- Patients with history of thrombosis including but not limited to myocardial infarction (MI)/stroke and pulmonary embolism (PE)/deep vein thrombosis (DVT) within 6 months of enrollment
- Active diarrhea due to inflammatory bowel disease or malabsorption syndrome
- Clinically significant uncontrolled illness
- Active, uncontrolled systemic infection (viral, bacterial, or fungal) requiring antibiotics
- Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
- Other active malignancy
- Females only: Pregnant or breastfeeding
- Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
Haris Ali, 626-218-2405, harisali@coh.org
Haris Ali
About this study
Official title: Phase 2a Study of Adding Ruxolitinib With Tacrolimus/Methotrexate Regimen for Graft-versus-Host Disease Prophylaxis in Myeloablative Conditioning Hematopoietic Cell Transplantation in Pediatric and Young Adult Patients
This phase II trial tests how well ruxolitinib with tacrolimus and methotrexate work to prevent the development 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. Ruxolitinib is a type of medication called a kinase inhibitor. It works by blocking the signals of cells that cause inflammation and cell proliferation, which may help prevent graft versus host disease (GVHD). Tacrolimus is a drug used to help reduce the risk of rejection by the body of organ and bone marrow transplants by suppressing the immune system. Methotrexate stops cells from making DNA, may kill cancer cells, and also suppress the immune system, which may reduce the risk of GVHD. Giving ruxolitinib with tacrolimus and methotrexate may prevent GVHD in pediatric and young adults undergoing allogeneic hematopoietic cell transplants.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine if the addition of ruxolitinib phosphate (ruxolitinib) to tacrolimus and methotrexate as graft-versus-host disease (GVHD) prophylaxis, is safe in pediatric and young adult patients with hematologic malignancies who are eligible to undergo allogeneic hematopoietic cell transplantation (HCT) from a matched donor. (Safety lead-in segment) II. Following a patient safety lead-in, evaluate the efficacy of ruxolitinib, when given as part of reduced intensity HCT from a matched related/unrelated donor, as assessed by 1 year graft-versus-host disease-free and relapse-free (GRFS) rates in pediatric and young adult patients. (Phase II segment)
SECONDARY OBJECTIVES:
- Estimate the cumulative incidence of acute GVHD (aGVHD) and non-relapse mortality (NRM) at 100-days after transplant.
II. Estimate the cumulative incidence of chronic GVHD (cGVHD) at 1- and 2-years after transplant.
III. Estimate the probabilities of overall and progression-free survival (OS/PFS) at 1- and 2-years after transplant.
IV. Estimate the relapse/progression rate. V. Estimate rate of infection and development of second malignancies including lymphoproliferative disorders at 1- and 2-years post-transplant.
VI. Further evaluate the safety of this regimen by assessing:
VIa. Adverse event type, frequency, severity, attribution, time-course, and duration; VIb. Complications including: infection, and delayed engraftment.
EXPLORATORY OBJECTIVES:
- Characterize and evaluate hematologic recovery, donor cell engraftment and immune reconstitution by cell count and flow cytometry of lymphocyte subsets.
II. Characterize changes in aGVHD biomarkers (Reg-3alpha, sTNF RI, IL2Ralpha), JAK-regulated pro-inflammatory cytokines (i.e. IL-6, TNFalpha, C-reactive protein [CRP], beta2Microglubuolin) and STAT3 phosphorylation (downstream of JAK signaling) over time and by aGVHD status/grade.
III. Evaluate the pharmacokinetics of ruxolitinib in pediatric and young adult patients.
OUTLINE:
Patients receive ruxolitinib orally (PO) twice daily (BID) from day -1 to day +100, tacrolimus intravenously (IV) on day -1, and methotrexate IV on days +1, +3, +6, and +11, and undergo HCT on day 0. Patients also undergo chest computed tomography (CT) and echocardiography (ECHO)/multigated acquisition scan (MUGA) at screening and undergo collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up at 30 days after the last dose of ruxolitinib and at 1 and 2 years post transplant.
- Being tested
- Biospecimen Collection, Chest Computed Tomography, Echocardiography, Hematopoietic Cell Transplantation, Methotrexate
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Chest Computed TomographyProcedure or surgery
Also called Chest CT, Computed Tomography of the Chest
Undergo chest CT
EchocardiographyProcedure or surgery
Also called EC
Undergo ECHO
Hematopoietic Cell TransplantationProcedure or surgery
Also called HCT, Hematopoietic Stem Cell Infusion, Hematopoietic Stem Cell Transplantation, HSCT
Undergo HCT
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IV
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA
Ruxolitinib PhosphateDrug
Also called INCB-18424 Phosphate, Jakafi, Jakavi
Given PO
TacrolimusDrug
Also called FK 506, FK-506, Fujimycin, Hecoria
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Prevention (Ruxolitinib, tacrolimus, methotrexate) | Experimental | Patients receive ruxolitinib PO BID from day -1 to day +100, tacrolimus IV on day -1, and methotrexate IV on days +1, +3, +6, and +11, and undergo HCT on day 0. Patients also undergo chest CT and ECHO/MUGA at screening and undergo collection of blood samples throughout the trial. Receives: Procedure: Biospecimen Collection; Procedure: Chest Computed Tomography; Procedure: Echocardiography; Procedure: Hematopoietic Cell Transplantation; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Ruxolitinib Phosphate; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Defined using the modified Bearman Scale and the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 scale.
Measured: Up to day +30 post hematopoietic cell transplant (HCT)
Graft-versus-host disease (GVHD)-free and relapse-free (GRFS)
Will be estimated using the product-limit method of Kaplan and Meier.
Measured: From the date of transplantation to the first time of observing the following events: grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death, assessed at 1 year post transplantation
Secondary outcomes (14)
Patients receiving planned doses of ruxolitinib (feasibility)
Patients who have received at least 80% of planned doses of ruxolitinib are deemed to meet feasibility criteria.
Measured: At completion of therapy (up to day+100)
Incidence of acute GVHD
Will be graded and staged according to Mount Sinai Acute GVHD International Consortium criteria. Will be estimated using the method described by Gooley et al (1999).
Measured: At 100 days post HCT transplant
Incidence of non-relapse mortality
Defined as death occurring in a patient from causes other than relapse or progression. Will be estimated using the method described by Gooley et al (1999).
Measured: At 100 days post HCT transplant
Incidence of chronic GVHD
Will be evaluated and scored according to National Institutes of Health Consensus Staging. Will be estimated using the method described by Gooley et al (1999).
Measured: At 1 and 2 years post HCT transplant
Overall survival
Will be estimated using the product-limit method of Kaplan and Meier.
Measured: From the day of stem cell infusion until death, up to 2 years
Progression free survival
Will be estimated using the product-limit method of Kaplan and Meier.
Measured: From the date of stem cell infusion to the date of death, disease relapse/progression, whichever occurs first, up to 2 years
incidence of relapse/progression
Will be estimated using the method described by Gooley et al (1999).
Measured: From day of stem cell infusion (day 0) to first observation of disease relapse/progression, up to 2 years
Infection rate
Will be reported by site of disease, date of onset, severity and resolution, if any.
Measured: From day -1 to day 130 post HCT transplant
Incidence of secondary malignancies
Measured: From day of stem cell infusion (day 0) to first observation of event of interest, assessed at 1 and 2 years post HCT transplant
Hematologic recovery, donor cell engraftment and immune reconstitution
Assessed using: absolute neutrophil count ≥ 0.5 x 10^3/uL achieved and sustained for 3 consecutive lab values on different days with no subsequent decline; platelets ≥ 20 K/uL independent of platelet transfusion support; immune reconstitution studies done by flow cytometry.
Measured: Up to 2 years
Incidence of adverse events during phase II segment
Defined using the modified Bearman Scale and the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 scale.
Measured: Up to day +30 post HCT transplant
Acute GVHD biomarkers
Measured: Up to 2 years
JAK-regulated pro-inflammatory cytokines
Measured: Up to 2 years
STAT3 phosphorylation
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2023
- Study start1 Aug 2024
- Primary completion22 Nov 2030 (estimated)
- Study completion22 Nov 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Haris Ali, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06128070
- Sponsor's protocol ID
- 23010
- Other IDs
- NCI-2023-07401, 23010, P30CA033572
- Status last verified
- Oct 2026
- First submitted
- 27 Oct 2023
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No