Adding Itacitinib to Cyclophosphamide and Tacrolimus for the Prevention of Graft Versus Host Disease in Patients Undergoing Hematopoietic Stem Cell Transplants

NCT05364762 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 21776NCI-2022-03765P30CA033572
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial evaluates the safety and effectiveness of adding itacitinib to cyclophosphamide and tacrolimus for the prevention of graft versus host disease (GVHD) in patients undergoing hematopoietic stem cell transplant. Itacitinib is an enzyme inhibitor that may regulate the development, proliferation, and activation of immune cells important for GVHD development. Cyclophosphamide and tacrolimus are immunosuppressive agents that may prevent GVHD in patients who receive stem cell transplants. Giving itacitinib in addition to cyclophosphamide and tacrolimus may be more effective at preventing GVHD in patients receiving hematopoietic stem cell transplants.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Primary Myelofibrosis; Secondary Myelofibrosis

Outcome Measures

Primary Outcomes (2)

• Number of participants with Grade III-IV acute graft versus host disease (GVHD)

  Acute GVHD will be graded and staged according to Mount Sinai Acute GVHD International Consortium (MAGIC) criteria.

  By day 100

• GVHD-free relapse-free survival rate

  Will be calculated using the Kaplan-Meier method.

  From start of hematopoietic cell transplantation to grade III-IV acute GvHD, chronic GvHD requiring systemic treatment, relapse, or death (from any cause), whichever occurs first, assessed at 1 year

Secondary Outcomes (19)

• Incidence of adverse events

  Up to 2 years

• Overall survival

  Day of stem cell infusion (day 0) until death or last follow-up, assessed at 100 days

• Overall survival

  Day of stem cell infusion (day 0) until death or last follow-up, assessed at 180 days

• Overall survival

  Day of stem cell infusion (day 0) until death or last follow-up, assessed at 1 year

• Progression free survival

  From the date of stem cell infusion to the date of death, disease relapse/progression, or last follow-up, assessed at 100 days

Study Arms (1)

Prevention (PBSCs, cyclophosphamide, itacitinib, tacrolimus)

EXPERIMENTAL

Patients undergo peripheral blood stem cell infusion on day 0. Patients receive cyclophosphamide IV QD on days 3 and 4, itacitinib PO QD on days 5-100, and tacrolimus IV or PO on days 6-65.

Drug: Cyclophosphamide; Drug: Itacitinib; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Quality-of-Life Assessment; Drug: Tacrolimus

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Prevention (PBSCs, cyclophosphamide, itacitinib, tacrolimus)

Itacitinib DRUG

Given PO

Also known as: INCB 039110, INCB-039110, INCB039110

Prevention (PBSCs, cyclophosphamide, itacitinib, tacrolimus)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo peripheral blood stem cell infusion

Also known as: PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell Transplantation, PERIPHERAL BLOOD STEM CELL TRANSPLANT, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Prevention (PBSCs, cyclophosphamide, itacitinib, tacrolimus)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Prevention (PBSCs, cyclophosphamide, itacitinib, tacrolimus)

Tacrolimus DRUG

Given IV or PO

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

Prevention (PBSCs, cyclophosphamide, itacitinib, tacrolimus)

Eligibility Criteria

• Age: Up to 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), 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
• Age: =\< 80 years
• Note: Patients \> 70 years of age must have Karnofsky performance status \>= 80 and HCT-comorbidity index (CI) =\< 2
• Karnofsky performance status \>= 70%
• Patients with the following diagnosis, eligible to undergo allogeneic HCT from an 8/8 match related/unrelated donor (A, B, C, DR by high resolution typing)
• Acute leukemias (acute myeloid leukemia \[AML\] or acute lymphoblastic leukemia \[ALL\]) in complete remission with bone marrow (BM) blast of \< 5%
• Myelofibrosis (MF): Primary or secondary with high- or intermediate-2 risk per Dynamic International Prognostic Scoring System (DIPSS)
• Myelodysplastic syndrome (blast \< 10%)
• Myeloproliferative neoplasm (MPN) other than MF needing HCT
• Chronic myelomonocytic leukemia (CMML)
• Total bilirubin =\< 2 x upper limit of normal (ULN) (unless has Gilbert's disease) (within 30 days prior to day 1 of protocol therapy unless otherwise stated)
• Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) \< 5 x ULN (within 30 days prior to day 1 of protocol therapy unless otherwise stated)

You may not qualify if:

• Prior allogeneic HCT
• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy
• Other investigational drugs for treatment of GVHD
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents
• Psychological issues, no appropriate caregivers identified, or non-compliant to medication
• Clinically significant uncontrolled illness
• Uncontrolled infection (bacterial, viral, fungal)
• 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

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Myeloproliferative Disorders; Primary Myelofibrosis

Interventions

Cyclophosphamide; itacitinib; INCB039110; Peripheral Blood Stem Cell Transplantation; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones

Study Officials

• Monzr M Al Malki

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 3, 2022
• First Posted: May 6, 2022
• Study Start: November 23, 2022
• Primary Completion (Estimated): May 22, 2026
• Study Completion (Estimated): May 22, 2026
• Last Updated: May 30, 2025

Record last verified: 2025-05

Locations

US (1)