Itacitinib With High-dose Posttransplantation Cyclophosphamide in Older Patients

NCT05823571 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: J2283IRB00298829
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Leukemia, Acute; Myelodysplastic Syndromes; Myelomonocytic Leukemia, Chronic; T-cell Prolymphocytic Leukemia; CML; Myeloproliferative Disorders; Multiple Myeloma; Plasma Cell Leukemia

Outcome Measures

Primary Outcomes (4)

• Number of participant deaths

  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

  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

  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

  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

Study Arms (1)

Itacitinib

EXPERIMENTAL

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.

Drug: Itacitinib

Interventions

Itacitinib DRUG

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.

Itacitinib

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Incyte Corporation: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Leukemia, Prolymphocytic, T-Cell; Myeloproliferative Disorders; Multiple Myeloma; Leukemia, Plasma Cell

Interventions

itacitinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Prolymphocytic; Leukemia, Lymphoid; Leukemia, T-Cell; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Study Officials

• Ivana Gojo, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2023
• First Posted: April 21, 2023
• Study Start: July 6, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: September 18, 2025

Record last verified: 2025-09

Locations

US (1)