Itacitinib (INCB039110) and Extracorporeal Photopheresis (ECP) for First-Line Treatment in Chronic GVHD

NCT04446182 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCI130090
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label, Phase II trial designed to assess the recommended phase 2 dose (RP2D) of itacitinib in combination ECP and efficacy of the combination after 24 weeks of therapy. The trial will consist of two parts: Part One will assess the RP2D. For dose-finding purposes, the dose limiting toxicity (DLT) evaluation period will be defined as the time from the first dose of itacitinib lead-in (7-day lead-in) to the last day of cycle one combination therapy (Cycle one day 28). Part Two will further describe and characterize the safety and efficacy of the regimen. The RP2D will be determined by a 3+3 dose de-escalation design. Should dose level one be deemed intolerable, enrollment will proceed at dose level -1. The RP2D will be affirmed according to the rules of the 3+3 dose de-escalation scheme. Once an RP2D has been confirmed, Part 2 will open as an expansion cohort. As this study was terminated after enrolling three patients out of an anticipated target accrual of 58, Part Two of this study did not occur.

Conditions

Chronic Graft-versus-host-disease

Outcome Measures

Primary Outcomes (2)

• Count of Participants With a Dose-limiting Toxicity (DLT) During the DLT Evaluation Period.

  Adverse events were assessed at each study visit from the first dose of itacitinib during the lead-in period (lead-in period = 5-10 days) until the last day of cycle one (each cycle = 28 days) of combination treatment with itacitinib and Extracorporeal Photopheresis (ECP). A DLT was defined as an Adverse Event (AE) that was 1) attributed as possibly, probably, or definitely related to itacitinib or to the combination of itacitinib and ECP, and 2) graded as "severe" or "life threatening" (grade 3 or 4) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.

  up to 38 days

• Count of Participants With a Response to Treatment at 24 Weeks of Treatment

  Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after 24 weeks of treatment. The criteria evaluates 9 organ systems, and then defines a partial response (PR) as at least one organ system with improvement since baseline and no worsening in other organs. Complete response (CR) is defined as an improvement in all affected organ systems to having no GVHD symptoms in any organ system. All responses must occur without any secondary systemic immunosuppressive therapy, and no malignancy recurrence or death. Participants with a PR or CR are counted as a response for this outcome.

  24 weeks

Secondary Outcomes (15)

• Count of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) During Study Treatment

  during study treatment - up to 1 year

• Count of Participants With a Response to Treatment After One Year of Treatment

  1 year

• Count of Participants With Failure Free Survival (FFS) at 24 Weeks and 1 Year

  24 weeks and 1 year

• Count of Participants Who Have Withdrawn All Immunosuppressants at 1 Year

  1 year

• Count of Participants With a Response to Treatment at 24 Weeks of Treatment Stratified by Concurrent Prednisone Use

  24 weeks

Study Arms (1)

Treatment: all patients

EXPERIMENTAL

Patients will self-administer itacitinib every morning regardless of food. ECP will be administered twice weekly on consecutive days for 8 weeks per institutional standards. At the end of 8 weeks of combination therapy, patients will start a standard ECP taper schedule and itacitinib will be continued at the assigned dose level. After six cycles of therapy, itacitinib may be tapered at the treating investigator's discretion as described below.

Drug: Itacitinib; Device: Extracorporeal Photopheresis (ECP)

Interventions

Itacitinib DRUG

All eligible patients will begin study therapy with approximately a week lead-in of itacitinib monotherapy at scheduled dose. Itacitinib will be taken daily at scheduled dose for a total of six cycles. Itacitinib may be tapered as deemed appropriate by the treating investigator. Patients will remain on study therapy as long as treatment discontinuation criteria are not met. Patients with Partial Response (PR) or better may continue itacitinib for up to 1 year.

Also known as: INCB039110

Treatment: all patients

Extracorporeal Photopheresis (ECP) DEVICE

ECP will begin after itacitinib lead in period. At the end of 8 weeks of combination therapy, patients will start a standard ECP taper schedule. Patients achieving PR or better after 6 cycles of itacitinib may continue treatment with itacitinib for up to 1 year. Thereafter, itacitinib may be tapered at the treating investigator's discretion.

Also known as: ECP

Treatment: all patients

Eligibility Criteria

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

You may qualify if:

• Male or female subject aged ≥ 18 years.
• Active, clinically diagnosed, moderate or severe chronic GVHD as defined by the NIH Consensus Development Project Criteria (See Appendix 2).
• History of an allogeneic hematopoietic cell transplant with any conditioning regimen, donor, or graft source.
• Need for systemic treatment for chronic GVHD as assessed by the treating investigator.
• No previous systemic treatment for chronic GVHD. Note: Participants may be receiving immunosuppressants for the prophylaxis or treatment of acute GVHD, but these medications must have been stable for at least 2 weeks prior to the initiation of study therapy. Prednisone dose (or its equivalent) should be at doses of ≤0.25 mg/kg/d for at least 2 weeks prior to the initiation of study therapy.
• Topical or inhaled treatments for chronic GVHD are allowed. Any prior ECP treatments for the management of acute GVHD must have occurred \> 4 weeks prior to the initiation of itacitinib treatment.
• Able to swallow and retain oral medication.
• Life expectancy \> 24 weeks.
• Karnofsky performance status ≥ 60
• Evidence of myeloid and platelet engraftment:
• Absolute neutrophil count ≥ 1000/microliter (mcL)
• Platelet count ≥ 25,000/mcL
• Adequate organ function as defined as:
• Hepatic:
• Total bilirubin ≤ 2 mg/dL

You may not qualify if:

• Subjects with score 3 lung GVHD; or biopsy-proven bronchiolitis obliterans.
• Participants have uncontrolled manifestations of acute GVHD.
• Treatment with any investigational medication within ≤ 30 days or 5 half-lives, whichever is longer, before the first dose of study drug.
• Patients who have received any previous systemic treatment for chronic GVHD, including corticosteroids, prior to Cycle 1, Day 1.
• Note: Prior and concomitant use of Calcineurin-Inhibitors (CNIs) for prevention and treatment of acute GVHD, as well as topical/inhaled steroids, is acceptable.
• Received prior Janus kinase (JAK) inhibitor therapy for any indication ≤ 4 weeks prior to Cycle 1 Day 1.
• Patients with relapsed or progressive malignant disease or any post-transplant lymphoproliferative disease.
• Chronic GVHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
• Inability to swallow food or any condition of the upper gastrointestinal tract that precludes the administration of oral medications.
• Any contraindication for extracorporeal photopheresis (ECP) per the treating investigator's discretion.
• Subject has a concurrent illness which in the opinion of the investigator may interfere with the treatment and evaluation of the subject.
• Pregnant or currently breast-feeding. Note: INCB039110 is a Janus kinase 1 (JAK1) inhibitor with the potential for serious or life-threatening birth defects or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with INCB039110, breastfeeding should be discontinued if the mother is treated with INCB039110. These potential risks may also apply to other agents used in this study.
• Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study drug and while on trial.
• Use of any prohibited concomitant medications as described in Section 6.5. A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment.
• Inadequate recovery from toxicity and/or complications from major surgery before starting therapy.

Sponsors & Collaborators

• University of Utah: lead
• Incyte Corporation: collaborator

Study Sites (1)

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

itacitinib; INCB039110; Photopheresis

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Results Point of Contact

• Title: Clinicaltrials.gov/CTRP Specialist
• Organization: Huntsman Cancer Institute/University of Utah

IITDataManagement@hci.utah.edu

8012136215

Study Officials

• Catherine Lee, MD

  Huntsman Cancer Institute

  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

Model Details: The RP2D will be determined by a 3+3 dose de-escalation design. Once an RP2D has been confirmed, Part 2 will open as an expansion cohort. (As this study was terminated after enrolling 3 patients, Part 2 of the planned study did not occur.)

Study Record Dates

• First Submitted: June 22, 2020
• First Posted: June 24, 2020
• Study Start: January 29, 2021
• Primary Completion: March 29, 2022
• Study Completion: January 30, 2023
• Last Updated: January 22, 2024
• Results First Posted: January 22, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)