Neoplasms

Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Rare Diseases

Neoplasm Metastasis

Syndrome

Leukemia

Preleukemia

Myelodysplastic Syndromes

Primary Myelofibrosis

Hematologic Diseases

Acute Disease

Neoplasms by Histologic Type

Bone Marrow Diseases

Precancerous Conditions

Myeloproliferative Disorders

Disease Attributes

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Fludarabine

Fludarabine phosphate

Melphalan

Tacrolimus

Sirolimus

Mechlorethamine

Nitrogen Mustard Compounds

Temsirolimus

MTOR Inhibitors

Immunosuppressive Agents

Immunologic Factors

Calcineurin Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Phenylalanine

Alanine

RIC: Patients receive fludarabine via infusion on days -9 to -5 and melphalan on day -4 in the absence of disease progression or unacceptable toxicity.

ALLOGENEIC HSCT: Patients undergo HSCT on day 0.

GVHD PROPHYLAXIS: Patients receive itacitinib PO QD beginning on day -3 and continuing until day 100 in the absence of disease progression or unacceptable toxicity. Patients also receive tacrolimus IV or PO and sirolimus PO beginning day -3 and continuing until day 100 with a taper in the absence of disease progression or unacceptable toxicity.

Itacitinib Adipate

Quality-of-Life Assessment

Questionnaire Administration

Haris Ali

This phase IIa trial studies the side effects of itacitinib when given together with standard treatment (tacrolimus and sirolimus), and to see how well it works in preventing graft-versus-host-disease (GVHD) in patients with acute leukemia, myelodysplastic syndrome or myelofibrosis who are undergoing reduced intensity conditioning donor stem cell transplantation. GVHD is a common complication after donor stem cell transplantation, resulting from donor immune cells recognizing recipients' cells and attacking them. Adding itacitinib to tacrolimus and sirolimus may reduce the risk GVHD and ultimately improve overall outcome and survival after donor stem cell transplantation.

PRIMARY OBJECTIVE:

I. Following a patient safety lead-in, estimate graft-versus-host disease free relapse free (GRFS) survival at 1- year post allogeneic stem cell transplantation (alloHCT).

SECONDARY OBJECTIVES:

I. Estimate the cumulative incidence of acute graft-versus-host disease (aGVHD) and non-relapse mortality (NRM) at 100-days post-transplant.

II. Estimate the cumulative incidence of chronic GVHD at 1- and 2-years post-transplant.

III. Estimate the probabilities of overall and progression-free survival (OS/PFS) at 1- and 2-years post-transplant.

IV. Estimate rate of infection and development of second malignancies including lymphoproliferative disorders at 1- and 2-years post-transplant.

V. Assess patients' quality of life (QOL) at day 100 and 1 year post alloHCT.

EXPLORATORY OBJECTIVES:

I. 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, TNF-RI, and ST2) and a composite biomarker panel (IL2Ralpha, TNF-R1, IL-8, and hepatocyte growth factor), JAK-regulated pro-inflammatory cytokines (i.e., IL-6, TNFalpha, CRP, Beta2 Microglobulin, and IFNgamma) and STAT3 phosphorylation (downstream of JAK signaling) over time and by aGVHD status/grade.

OUTLINE:

REDUCED INTENSITY CONDITIONING (RIC): Patients receive fludarabine via infusion on days -9 to -5 and melphalan on day -4 in the absence of disease progression or unacceptable toxicity.

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT): Patients undergo HSCT on day 0.

GVHD PROPHYLAXIS: Patients receive itacitinib orally (PO) once daily (QD) beginning on day -3 and continuing until day 100 in the absence of disease progression or unacceptable toxicity. Patients also receive tacrolimus intravenously (IV) or PO and sirolimus PO beginning day -3 and continuing until day 100 with a taper in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then periodically for up to 2 years post- transplantation.

Itacitinib, Tacrolimus, and Sirolimus for the Prevention of GVHD in Patients With Acute Leukemia, Myelodysplastic Syndrome, or Myelofibrosis Undergoing Reduced Intensity Conditioning Donor Stem Cell Transplantation

Phase IIa Study of Addition of Itacitinib With Tacrolimus/Sirolimus Regimen for GVHD Prophylaxis in Fludarabine and Melphalan Non-Myeloablative Conditioning Hematopoietic Cell Transplantation for Acute Leukemias, MDS or MF

GRFS is defined as time from the date of transplantation to the first time of observing following events: grade 3-4 acute graft versus host disease (GVHD), chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first. Kaplan-Meier curve will be generated for GRFS.

Acute GVHD will be graded and staged according to the Consensus Grading.

Kaplan-Meier curve will be generated for PFS.

National Cancer Institute (NCI)

City of Hope Medical Center

RIC: Patients receive fludarabine via infusion on days -9 to -5 and melphalan on day -4 in the absence of disease progression or unacceptable toxicity.

ALLOGENEIC HSCT: Patients undergo HSCT on day 0.

GVHD PROPHYLAXIS: Patients receive itacitinib PO QD beginning on day -3 and continuing until day 100 in the absence of disease progression or unacceptable toxicity. Patients also receive tacrolimus IV or PO and sirolimus PO beginning day -3 and continuing until day 100 with a taper in the absence of disease progression or unacceptable toxicity.

Fludarabine: Given via infusion

Itacitinib Adipate: Given PO

Melphalan: Given IV

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Sirolimus: Given PO

Tacrolimus: Given IV or PO

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Itacitinib, Tacrolimus, and Sirolimus for the Prevention of GVHD in Patients With Acute Leukemia, Myelodysplastic Syndrome, or Myelofibrosis Undergoing Reduced Intensity Conditioning Donor Stem Cell Transplantation	NCT04339101	Acute Leukemia Hematologic and... Myelodysplastic... Primary Myelofi... Secondary Myelo...	Fludarabine Itacitinib Adip... Melphalan Quality-of-Life... Questionnaire A... Sirolimus Tacrolimus	18 Years - 75 Years	City of Hope Medical Center
Itacitinib, Tacrolimus, and Sirolimus for the Prevention of GVHD in Patients With Acute Leukemia, Myelodysplastic Syndrome, or Myelofibrosis Undergoing Reduced Intensity Conditioning Donor Stem Cell Transplantation	NCT04339101	Acute Leukemia Hematologic and... Myelodysplastic... Primary Myelofi... Secondary Myelo...	Fludarabine Itacitinib Adip... Melphalan Quality-of-Life... Questionnaire A... Sirolimus Tacrolimus	18 Years - 75 Years	City of Hope Medical Center
Itacitinib, Tacrolimus, and Sirolimus for the Prevention of GVHD in Patients With Acute Leukemia, Myelodysplastic Syndrome, or Myelofibrosis Undergoing Reduced Intensity Conditioning Donor Stem Cell Transplantation	NCT04339101	Acute Leukemia Hematologic and... Myelodysplastic... Primary Myelofi... Secondary Myelo...	Fludarabine Itacitinib Adip... Melphalan Quality-of-Life... Questionnaire A... Sirolimus Tacrolimus	18 Years - 75 Years	City of Hope Medical Center

Spots Global Cancer Trial Database for itacitinib adipate