Status and phase
Conditions
Treatments
About
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.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
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:
Note: Use of growth factors and transfusion support is allowed during the study; however, growth factors and transfusion support to reach a minimum absolute neutrophil count (ANC) or platelet count for inclusion are not allowed within the 7 days before the screening laboratory assessment.
Adequate organ function as defined as:
Hepatic:
Renal:
---estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 as calculated using the Modification of Diet in Renal Disease formula or by the Cockcroft-Gault formula:
Coagulation:
Willingness to avoid pregnancy or father children based on the criteria below and as described in Section 5.4.2:
Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Exclusion criteria
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.
Unwillingness to be transfused with blood components during the study.
History of other malignancy (not including the underlying malignancy that was the indication for the transplant), with the following exceptions:
The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
History of thromboembolic event within 1 month before study registration.
HIV-infected patients on effective antiretroviral therapy with an undetectable viral load within 6 months are eligible for this trial.
Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment, or at risk for HBV reactivation (i.e., positive HBsAg). Participants with negative HBsAg and positive total hepatitis B core antigen (HBc) antibody may be included if HBV DNA is undetectable at the time of screening. Participants who are positive for HCV antibodies are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. Participants whose immune status is unknown or uncertain must have results confirming immune status before enrollment. Serology results performed less than or equal to 6 months prior to the first planned dose of itacitinib are acceptable for determining eligibility.
Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3).
Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug/treatment and attending required study visits; pose a significant risk to the participant; or interfere with the interpretation of study data.
Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations) per the investigator's assessment.
Primary purpose
Allocation
Interventional model
Masking
3 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal