Golidocitinib in Patients With Mycosis Fungoides/Sézary Syndrome and T-Cell Large Granular Lymphocytic Leukemia (GEMSTONE)

A Pilot Study of Golidocitinib, a JAK1 Inhibitor, in Patients With Mycosis Fungoides/Sézary Syndrome and T-Cell Large Granular Lymphocytic Leukemia (GEMSTONE)

This is an open-label, single-institution pilot study of single-agent golidocitinib enrolling up to 24 patients in two cohorts: a) advanced-stage mycosis fungoides/Sézary syndrome (MF/SS), n=12, or b) T-cell large granular lymphocytic leukemia (T-LGLL) requiring treatment, n=12. Patients will receive single agent golidocitinib at the previously established dose of 150 mg QD as determined in the phase I and II studies of golidocitinib.

Study Overview

• Status: Not yet recruiting
• Conditions: T-cell Large Granular Lymphocytic Leukemia; Mycosis Fungoides/Sezary Syndrome
• Intervention / Treatment: Drug: Golidocitinib

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Neha Mehta-Shah, MD; Phone Number: 557-747-2108; Email: mehta-n@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
      • Principal Investigator: Neha Mehta-Shah, MD
      • Sub-Investigator: Fei Wan, PhD
      • Contact: Neha Mehta-Shah, MD; Phone Number: 557-747-2108; Email: mehta-n@wustl.edu
      • Sub-Investigator: Hunter C Cochran, MD
      • Sub-Investigator: Todd Fehniger, MD, PhD
      • Sub-Investigator: Jacqueline Payton, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for MF/SS:

• Histologically or cytologically confirmed mycosis fungoides or Sézary syndrome, stages IB to IVB with measurable disease and/or detectable blood involvement based on the Global Response Criteria for CTCL
• Received at least one prior line of systemic therapy.
• At least 18 years of age.
• ECOG performance status ≤ 2

• Adequate counts and organ function as defined below:

  • Platelet count > 75 K/cumm, unless related to lymphoma, in which case platelet count must be > 50 K/cumm. Platelet transfusion may be utilized to meet inclusion criteria, as long as the platelet count remains at the above threshold without transfusion for 5 days.
  • Serum Creatinine ≤ 2 x IULN
  • Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min using the Modification of Diet in Renal Disease (MDRD) equation (multiplying eGFR by each subject's Body Surface Area [BSA])
  • Serum total bilirubin ≤ 1.5 x IULN if no liver involvement, or ≤ 2 x IULN in the presence of Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver involvement.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x IULN, or ≤ 5 x IULN if documented hepatic involvement with lymphoma.
• Patients must be able to swallow pills.
• The effects of golidocitinib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use highly effective methods of contraception for the duration of study participation and for 3 months after the last dose of golidocitinib for female patients and female partners of male patients, or for 6 months after the last dose of golidocitinib for male patients and male partners of female patients. Should a woman become pregnant or suspect she is pregnant or a male patient suspect he has impregnated another while participating in this study, s/he must inform the treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Inclusion Criteria for LGLL

-Diagnosis of T-LGLL defined as: CD3+CD8+ cell population > 650/mm3 or CD3+CD8+CD57+ population > 500/mm3 and the presence of a clonal T-cell receptor (within 1 month of diagnosis).

Note: patients with MDS-like T-LGLL may be included with PI approval even if CD3+CD8+ cell population is < 650/mm3, though +TCR is required. Natural-Killer (NK) LGL is also permitted, provided there is a clonal NK-cell population noted with > 500 cells/mm3.

• Untreated T-LGLL or failed at least one line of frontline therapy.

• Patients must require treatment for T-LGLL, as defined by meeting one or more of the below criteria:

  • Symptomatic anemia with hemoglobin < 10 g/dL
  • Transfusion-dependent anemia
  • Neutropenia with absolute neutrophil count (ANC) < 0.5 K/cumm
  • Neutropenia with ANC < 1.5 K/cumm with recurrent infections
• At least 18 years of age.
• ECOG performance status ≤ 2

• Adequate counts and organ function as defined below:

  • Platelet count > 50 K/cumm. Platelet transfusion may be utilized to meet inclusion criteria, as long as the platelet count remains > 50 K/cumm within 5 days of last transfusion.
  • Serum Creatinine ≤ 2 x IULN
  • Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min using the Modification of Diet in Renal Disease (MDRD) equation (multiplying eGFR by each subject's Body Surface Area [BSA])
  • Serum total bilirubin ≤ 1.5 x IULN if no liver involvement, or ≤ 2 x IULN in the presence of Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver involvement.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x IULN, or ≤ 5 x IULN if documented hepatic involvement with T-LGLL.
• Patients with treated brain metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression.
• Patients must be able to swallow pills.
• The effects of golidocitinib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use highly effective methods of contraception for the duration of study participation and for 3 months after the last dose of golidocitinib for female patients and female partners of male patients, or for 6 months after the last dose of golidocitinib for male patients and male partners of female patients. Should a woman become pregnant or suspect she is pregnant or a male patient suspect he has impregnated another while participating in this study, s/he must inform the treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria for MF/SS:

• Patients with active CNS lymphoma.
• A history of other malignancy, with the exception of prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Currently receiving any other investigational agents.

• Concomitant use of another systemic therapy for MF/SS. Patients must have the following minimum washout from previous treatments:

  • At least 8 weeks for low-dose (12 Gy or less) total skin electron beam therapy (TSEBT).
  • At least 4 weeks for systemic cytotoxic anticancer agents or for tumor-targeting monoclonal antibodies (mAbs), with the exception of alemtuzumab, for which the washout is at least 16 weeks.
  • At least 2 weeks or 5 half-lives (whichever is shorter) for systemic retinoids, interferons, vorinostat, romidepsin, and denileukin diftitox, or anticancer investigational agents that are not defined as immunotherapy.
  • At least 1 week for topical retinoids, nitrogen mustard, or imiquimod.
• Gastrointestinal disorders, or any other condition that may significantly interfere with absorption of the study medication by the investigator's assessment.
• Uncontrolled active infection requiring IV antibiotic, antiviral, or antifungal medications within 14 days before the first dose of study drug. Infections (e.g., urinary tract infection) controlled on concurrent antimicrobial agents and antimicrobial prophylaxis per institutional guidelines are acceptable.

• Current known active or chronic infection with HIV, hepatitis B, or hepatitis C. All patients will require serologic testing to be performed within 6 months prior to C1D1.

  • Patients with chronic HBV are defined as patients with positive hepatitis B serology: Patients with a negative HBsAg and a positive HBcAb require an undetectable/negative hepatitis B DNA test (e.g. polymerase chain reaction [PCR] test) to be enrolled and will require prophylactic antiviral treatment initiated prior to the first dose of study drug, and continued until approximately 6 to 12 months after completion of study drug(s).
  • Patients with chronic HCV infection are defined as patients with a positive hepatitis C antibody (anti-HCV) test:
  • Patients with a positive anti-HCV antibody test require a quantitative HCV RNA viral load test (e.g., polymerase chain reaction [PCR] test) to determine eligibility. Patients with a positive anti-HCV antibody and a detectable/positive HCV RNA (i.e., active chronic HCV infection) are not eligible.
  • Patients with a positive anti-HCV antibody and an undetectable/negative HCV RNA (i.e., prior resolved infection or previously treated and cured HCV) are eligible for enrollment without antiviral treatment.
• Unstable or severe uncontrolled medical condition or any important medical or psychiatric illness or abnormal laboratory finding that would, in the investigator's judgment, increase the risk to the patient associated with his/her participation in this study.
• Pregnant and/or breastfeeding.
• Concurrent immune-suppressive therapy exceeding prednisone 20 mg equivalent.

Exclusion Criteria for LGLL

• Patients with active CNS involvement with T-LGLL.
• A history of other malignancy with the exception of prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Currently receiving any other investigational agents, or receipt of another systemic therapy for T-LGLL within 14 days or 5 half-lives of the first dose of golidocitinib, whichever is shorter.
• Gastrointestinal disorders, or any other condition that may significantly interfere with absorption of the study medication by the investigator's assessment.
• Uncontrolled active infection requiring IV antibiotic, antiviral, or antifungal medications within 14 days before the first dose of study drug. Infections (e.g., urinary tract infection) controlled on concurrent antimicrobial agents and antimicrobial prophylaxis per institutional guidelines are acceptable.

• Current known active or chronic infection with HIV, hepatitis B, or hepatitis C. All patients will require serologic testing to be performed within 6 months prior to C1D1.

  • Patients with chronic HBV are defined as patients with positive hepatitis B serology: Patients with a negative HBsAg and a positive HBcAb require an undetectable/negative hepatitis B DNA test (e.g. polymerase chain reaction [PCR] test) to be enrolled and will require prophylactic antiviral treatment initiated prior to the first dose of study drug, and continued until approximately 6 to 12 months after completion of study drug(s).
  • Patients with chronic HCV infection are defined as patients with a positive hepatitis C antibody (anti-HCV) test: Patients with a positive anti-HCV antibody test require a quantitative HCV RNA viral load test (e.g., polymerase chain reaction [PCR] test) to determine eligibility. Patients with a positive anti-HCV antibody and a detectable/positive HCV RNA (i.e., active chronic HCV infection) are not eligible. AND Patients with a positive anti-HCV antibody and an undetectable/negative HCV RNA (i.e., prior resolved infection or previously treated and cured HCV) are eligible for enrollment without antiviral treatment.
• Unstable or severe uncontrolled medical condition or any important medical or psychiatric illness or abnormal laboratory finding that would, in the investigator's judgment, increase the risk to the patient associated with his/her participation in this study.
• Pregnant and/or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Advanced-stage mycosis fungoides/Sézary syndrome (MF/SS) - Golidocitinib; Patients with advanced-stage MF/SS will take golidocitinib as a 150 mg pill orally each day of a 28-day cycle.	Drug: Golidocitinib; Golidocitinib is a JAK1 kinase inhibitor taken orally at a dose of 150mg.
Experimental: Cohort 2: T-cell large granular lymphocytic leukemia (T-LGLL) - Golidocitinib; Patients with T-LGLL will take golidocitinib as a 150 mg pill orally each day of a 28-day cycle.	Drug: Golidocitinib; Golidocitinib is a JAK1 kinase inhibitor taken orally at a dose of 150mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as the proportion of evaluable patients achieving complete response (CR) or partial response (PR). As assessed according to the Global Response Criteria for CTCL and E5998 prospective clinical trial for T-LGLL.	At four months after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best overall response rate	Best overall response rate is defined by the best response of a given patient while being evaluated on study as assessed according to the Global Response Criteria for CTCL and E5998 prospective clinical trial (NCT03239392) for T-LGLL	Through completion of treatment (estimated to be 12 months)
Complete response rate	Complete response rate is defined as the percentage of patients treated achieving a complete response (CR) as assessed according to the Global Response Criteria for CTCL and E5998 prospective clinical trial (NCT03239392) for T-LGLL.	Through completion of treatment (estimated to be 12 months)
Duration of response	Duration of response is defined as the time from first initial response to progression of disease as assessed according to the Global Response Criteria for CTCL and E5998 prospective clinical trial (NCT03239392) for T-LGLL.	From date of first response through disease progression (estimated to be 22 months)
Time to maximum response	Time to maximum response is defined by the time from initiation of study therapy to the time to achieve the best response as assessed according to the Global Response Criteria for CTCL and E5998 prospective clinical trial (NCT03239392) for T-LGLL.	Through completion of treatment (estimated to be 12 months)
Clinical benefit rate	Clinical benefit rate is defined by the percentage of patients treated who have achieved a complete response (CR), partial response (PR) or have stable disease (SD) for 6 months or greater as assessed according to the Global Response Criteria for CTCL and E5998 prospective clinical trial (NCT03239392) for T-LGLL.	Through completion of treatment (estimated to be 12 months)
Frequency and grades of treatment-emergent adverse events (TEAE)	As assessed by CTCAE v6.0	From start of treatment through start of new treatment or 30 days after completion of treatment, whichever is earlier (estimated to be 13 months)
Rate of treatment discontinuation due to TEAE	As assessed by CTCAE v6.0	Through completion of treatment (estimated to be 12 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Dizal Pharmaceuticals
• Investigators: Principal Investigator: Neha Mehta-Shah, MD, Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): January 31, 2030
• Study Completion (Estimated): September 30, 2032

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: JAK inhibitor; Cutaneous T-cell lymphoma; Golidocitinib
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia, Lymphoid; Leukemia; Leukemia, T-Cell; Lymphoma, T-Cell; Hemic and Lymphatic Diseases; Lymphoma, T-Cell, Cutaneous; Leukemia, Large Granular Lymphocytic; Mycosis Fungoides; Sezary Syndrome
• Other Study ID Numbers: 26-x150

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No