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 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 19576NCI-2020-01722
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Leukemia; Hematologic and Lymphocytic Disorder; Myelodysplastic Syndrome; Primary Myelofibrosis; Secondary Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• Graft-versus-host Disease Free Relapse Free (GRFS) at 1 Year

  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.

  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, assessed at 1 year post transplant.

Secondary Outcomes (2)

• Cumulative Incidence of Grade II-IV Acute GVHD

  From day 0 (date of stem cell infusion) through 100 days post-transplant

• Progression Free Survival (PFS)

  From the date of stem cell infusion to the date of death, disease relapse/progression, or last follow-up, whichever occurs first, assessed at 1 year post transplant

Study Arms (1)

Treatment (itacitinib adipate, tacrolimus, sirolimus)

EXPERIMENTAL

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.

Drug: Fludarabine; Drug: Itacitinib Adipate; Drug: Melphalan; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Sirolimus; Drug: Tacrolimus

Interventions

Fludarabine DRUG

Given via infusion

Also known as: Fluradosa

Treatment (itacitinib adipate, tacrolimus, sirolimus)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine nitrogen mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (itacitinib adipate, tacrolimus, sirolimus)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (itacitinib adipate, tacrolimus, sirolimus)

Questionnaire Administration OTHER

Ancillary studies

Treatment (itacitinib adipate, tacrolimus, sirolimus)

Itacitinib Adipate DRUG

Given PO

Also known as: INCB-039110 Adipate, INCB039110 Adipate

Treatment (itacitinib adipate, tacrolimus, sirolimus)

Sirolimus DRUG

Given PO

Also known as: AY 22989, RAPA, Rapamune, rapamycin, SILA 9268A, WY-090217

Treatment (itacitinib adipate, tacrolimus, sirolimus)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (itacitinib adipate, tacrolimus, sirolimus)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 principal investigator (PI) approval
• Performance status: Karnofsky \>= 70%
• Patients with neoplastic hematologic disorders with indication of allogeneic transplant according to the standard guidelines as follows:
• Acute leukemia (AL) in first complete response (CR1) or subsequent complete response (CR) or active disease with bone marrow (BM) blast of \< 5%
• Myelodysplastic syndrome (MDS) with intermediate-2 or high risk per International Prognostic Scoring System (IPSS) or
• Myelofibrosis; primary or secondary if intermediate-2 or high risk per Dynamic International Prognostic Scoring System (DIPPS)
• All candidates for this study must have a matched related donor (MRD) who is willing to donate BM or peripheral blood stem cells or an 8/8 allele matched unrelated donor (MUD)
• Total bilirubin =\< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated. In case of active disease, evaluation should be done within 15 days)
• Aspartate aminotransferase (AST) =\< 2.5 x ULN (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated. In case of active disease, evaluation should be done within 15 days)
• Alanine aminotransferase (ALT) =\< 2.5 x ULN (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated. In case of active disease, evaluation should be done within 15 days)
• Creatinine clearance of \>= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated. In case of active disease, evaluation should be done within 15 days)
• Left ventricular ejection fraction (LVEF) \>= 50%

You may not qualify if:

• Chemotherapy, radiation therapy, biological therapy, and/or immunotherapy within 21 days prior to day 1 of protocol therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Psychological issues, no appropriate caregivers identified, or non-compliant to medication
• Uncontrolled medical or psychiatric disorders which may preclude patients to undergo clinical studies (Discretion of the attending physician)
• Active diarrhea due to inflammatory bowel disease or malabsorption syndrome
• Clinically significant uncontrolled illness
• Active, uncontrolled systemic infection (bacterial, viral, or fungal) requiring antibiotics
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• Diagnosis of Gilbert's disease
• 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)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Hematologic Diseases; Myelodysplastic Syndromes; Primary Myelofibrosis

Interventions

fludarabine; Melphalan; Sirolimus; Tacrolimus

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Macrolides; Lactones

Results Point of Contact

• Title: Dr. Ali Haris
• Organization: City of Hope Medical Center

aharis@coh.org

626-359-8111

Study Officials

• Haris Ali

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2020
• First Posted: April 9, 2020
• Study Start: November 11, 2020
• Primary Completion: May 22, 2023
• Study Completion: October 9, 2025
• Last Updated: March 30, 2026
• Results First Posted: September 13, 2023

Record last verified: 2026-03

Locations

US (1)