- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05823571
Itacitinib With High-dose Posttransplantation Cyclophosphamide in Older Patients
March 7, 2024 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phase 1a/1b Study of Itacitinib (INCB039110) for Cytokine Release Syndrome Prevention and Minimization of Immunosuppression Following Nonmyeloablative Related Partially HLA-mismatched Peripheral Blood Stem Cell Transplant (PBSCT) With High-dose Posttransplantation Cyclophosphamide in Older Patients (Age 60 Years)
This research is being done to learn whether drug called itacitinib, which is a novel inflammation- and immune-lowering drug (immunosuppressant), can be given before and after non-myeloablative peripheral blood stem cell transplantation (PBSCT; also known as a 'mini' transplant) to help prevent certain complications such as cytokine release syndrome (CRS) for patients with blood cancers, using peripheral blood from a relative.
The investigators will also examine if by using itacitinib the investigators can reduce the duration of MMF (other immune suppressive drug administration posttransplant).
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
The NMA PBSC haplo transplant is associated with a higher risk of morbidity and mortality from the cytokine (IL-6 and others)-driven CRS and perhaps higher incidence of acute and chronic GVHD compared to bone marrow (BM) haplo allografting with post-transplant cyclophosphamide (PTCy).
Notably, severe CRS (grade 3 and higher) appears to be more common in older patients (≥ 60 years) and is associated with significantly higher non-relapse mortality (NRM) in this patient group.
Itacitinib has demonstrated safety, tolerability, ability to inhibit cytokines, including IL-6.
Data also suggest that itacitinib can be administered safely in peri- and post-transplant period in the setting of Posttransplant CY immune prophylaxis and haploPBSCT with no evidence of delayed engraftment or delayed count recovery, with significant reduction in CRS compared to historical control, and a low rate of aGVHD, cGVHD, and NRM, and with no increase in relapse risk.
Thus, the investigators propose a clinical study in which itacitinib will be used prophylactically in recipients age 60 years and older to prevent development of severe CRS, reduce severe CRS-associated NRM, and the incidence of severe GVHD, thus allowing further reduction in posttransplant immunosuppression therapy after PTCy-based NMA related partially-mismatched PB allografting.
Study Type
Interventional
Enrollment (Estimated)
32
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Ivana Gojo, MD
- Phone Number: 410-502-8775
- Email: igojo1@jhmi.edu
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21231
- Recruiting
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
-
Contact:
- Ivana Gojo, MD
- Phone Number: 410-502-8775
- Email: igojo1@jh.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Presence of a suitable related, HLA-haploidentical (partially mismatched) stem cell donor.
Eligible diagnoses:
- Acute leukemias in complete remission with minimal residual disease
- Myelodysplastic syndrome (MDS) with at least one poor-risk feature
- Chronic myelomonocytic leukemia with at least one poor-risk feature
- T-cell PLL in PR or better prior to transplantation.
- Tyrosine kinase-refractory CML in first chronic phase, TKI-intolerant CML in first chronic phase, or CML in second or subsequent chronic phase.
- Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)
- Multiple myeloma or plasma cell leukemia with a PR or better to the last treatment regimen
- Age ≥ 60 years.
Adequate end-organ function as measured by:
- Left ventricular ejection fraction ≥ 35% or shortening fraction > 25%
- Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST ≤ 5 x ULN
- FEV1 and FVC ≥ 40% of predicted
- ECOG performance status ≤ 2 or Karnofsky score ≥ 60
Exclusion Criteria:
- No active extramedullary leukemia or known active CNS involvement by malignancy.
- Any previous autologous HSCT must have occurred at least 3 months prior to start of conditioning.
- No previous allogeneic HSCT.
- Not pregnant or breast-feeding
- No uncontrolled infection.
- No known HIV infection.
- No active replicating HBV or HCV infection detected by PCR that requires treatment or at risk for HBV reactivation (positive HBsAg)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Itacitinib
Itacitinib will be given at 200 mg orally daily from day -3 to day 90.
Itacitinib will be given in conjunction with one of four different regimens for immunosuppression.
These 4 regimens are listed in Table 2, Section 5.2 of the protocol.
Itacitinib may continue beyond day +90 if there is GVHD.
NOTE: If patient develops GVHD requiring treatment after all immune suppression, including itacitinib, is stopped on day +90, the itacitinib will not be restarted and the patient will be treated per standard of care.
|
A standard 3+3 design will be used to evaluate the safety of itacitinib plus different immunosuppression regimens.
This study has four predefined Regimens that will be explored in the optimal Regimen-finding phase and are listed in Table 2 of the protocol.
Itacitinib will be given in conjunction with each of four different regimens for immunosuppression.
Regimen 1 is the current standard for our BMT patients, with a duration of MMF from day 5-35.
Regimen 2 will decrease the duration of MMF from 35 to day 25.
Regimen 3 will decrease the duration of MMF from 35 to day 15.
Regimen 4 will eliminate MMF altogether.
We will start with Regimen 1, which combines itacitinib with the current standard of immunosuppression.
Progression through cohorts (Regimens) will be based on a standard 3+3 design to find the optimal regimen.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participant deaths
Time Frame: 14 days
|
Number of participant deaths will be used to assess the efficacy of itacitinib in preventing the occurrence of death.
|
14 days
|
Number of participants with grade 3 or higher CRS
Time Frame: 14 days
|
Number of participants with grade 3 or higher CRS will be used to assess the efficacy of itacitinib in preventing the development of severe (grade 3 or higher) cytokine release syndrome (CRS).
|
14 days
|
Number of participants with grade 1-2 CRS that requires additional CRS-directed treatment
Time Frame: 14 days
|
Number of participants with grade 1-2 CRS that requires additional CRS-directed treatment will be used to assess the efficacy of itacitinib in preventing the development of grade 1-2 CRS that requires additional CRS-directed treatment.
|
14 days
|
Number of participants with treatment limiting toxicities by Day 60
Time Frame: 60 days
|
Number of participants with treatment limiting toxicities by Day 60 will be used to identify the safe PTCy-based immunosuppressive regimen that incorporates itacitinib with tacrolimus and a reduced duration of immunosuppression with mycophenolate (MMF).
|
60 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Ivana Gojo, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 6, 2023
Primary Completion (Estimated)
March 1, 2028
Study Completion (Estimated)
March 1, 2030
Study Registration Dates
First Submitted
April 10, 2023
First Submitted That Met QC Criteria
April 10, 2023
First Posted (Actual)
April 21, 2023
Study Record Updates
Last Update Posted (Actual)
March 8, 2024
Last Update Submitted That Met QC Criteria
March 7, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia, Lymphoid
- Leukemia, Myeloid
- Leukemia, T-Cell
- Chronic Disease
- Myelodysplastic Syndromes
- Multiple Myeloma
- Leukemia
- Leukemia, Myelomonocytic, Chronic
- Myeloproliferative Disorders
- Leukemia, Prolymphocytic
- Leukemia, Plasma Cell
- Leukemia, Prolymphocytic, T-Cell
Other Study ID Numbers
- J2283
- IRB00298829 (Other Identifier: JHMIRB)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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