Oral Azacitidine for the Treatment of Relapsed or Refractory T-cell Large Granular Lymphocytic Leukemia

NCT05141682 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-21018NCI-2021-08491
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial studies the best dose, possible benefits and/or side effects of oral azacitidine in treating patients with T-cell large granular lymphocytic leukemia that has come back (relapsed) or has not responded to previous treatment (refractory). Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

T-Cell Large Granular Lymphocyte Leukemia

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of oral azacitidine (CC-486) (Phase I)

  Up to 4 cycles (1 cycle = 28 days)

• Overall response rate (complete response [CR] + partial response [PR]) (Phase II)

  Assessed by the investigator based upon criteria derived from the ECOG 5998 and BNZ-1 clinical trials.

  Up to 3 years

Secondary Outcomes (9)

• Duration of response to CC-486

  Up to 3 years

• Progression-free survival (PFS

  Up to 3 years

• Rate of conversion from PR at 4 months to CR at 8 months

  From 4 months to 8 months

• Rate of conversion from PR at 4 months to CR at 12 months

  From 4 months to 12 months

• Rate of molecular remission (T-cell receptor [TCR] clearance, STAT3 mutation clearance)

  At 4 months

Study Arms (1)

Treatment (Oral Azacitidne)

EXPERIMENTAL

Patients will receive CC-486 orally (PO) D1-14 of a 28-day cycle, in a similar fashion to the QUAZAR study for a minimum of 4 cycles. Patients that achieve a response (CR or PR) will remain on study for a maximum of 12 months. Patients without a response at 4 months will come off the study.

Drug: Oral Azacitidine

Interventions

Oral Azacitidine DRUG

Given PO

Also known as: CC-486

Treatment (Oral Azacitidne)

Eligibility Criteria

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

You may qualify if:

• Age 18 or older
• Diagnosis of T-LGLL defined as: CD3+CD8+ cell population \> 650/mm\^3 and the presence of a clonal T-cell receptor (within 1 month of diagnosis). This also includes patients with rare T-LGLL variants include CD4+ T-LGLL, and gamma/delta T-LGLL which can be CD4- and CD8, though patients still must have an LGL cell population \>500 cells/mm3 and the presence of a clonal T-cell receptor within 1 month of diagnosis or relapse. Note: patients with myelodysplastic syndrome (MDS)-like T-LGLL may be included with principal investigator (PI) approval even if CD3+CD8+ cell population is \< 650/mm\^3, though +TCR is required. Natural-killer (NK) large granular lymphocytic leukemia (LGL) is also permitted, provided there is a clonal NK-cell population noted with \> 500 cells/mm\^3
• Failed at least one line of frontline therapy; off treatment for at least 14 days or 5 half-lives, whichever is longer
• Require Treatment for T-LGLL (One or more required)
• Symptomatic anemia with hemoglobin \< 10 g/dL
• Transfusion-dependent anemia
• Neutropenia with absolute neutrophil count (ANC) \< 500/mm\^3
• Neutropenia with ANC \< 1500/mm\^3 with recurrent infections
• Platelet count \>= 50 x 10\^9/L
• Serum creatinine =\< 2 x the upper limit of normal (ULN)
• Total bilirubin =\< 1.5 x ULN (patients with Gilbert's syndrome with a bilirubin \> 1.5 x ULN permitted)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 1.5 x ULN
• Eastern cooperative oncology group (ECOG) performance status =\< 2
• Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study
• Able to sign informed consent

You may not qualify if:

• Active Infection requiring ongoing anti-microbial treatment. Patients with human immunodeficiency virus (HIV), positive hepatitis B surface antigen or hepatitis C antibody will be excluded
• Concurrent immune-suppressive therapy (prednisone or equivalent up to 20 mg permitted to treat T-LGL symptoms, but must be weaned within one month of initiation of trial drug). Patients on stable, chronic prednisone =\< 10 mg for rheumatologic/autoimmune conditions are exempted from this requirement. They may enroll on the study
• Active, concurrent malignancy unless deemed related to T-LGLL by PI
• Prior use of 5-azacytidine or decitabine
• Positive pregnancy test

Sponsors & Collaborators

• Jonathan Brammer: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Large Granular Lymphocytic

Interventions

Azacitidine; cc-486

Condition Hierarchy (Ancestors)

Leukemia, T-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Jonathan Brammer, MD

  Ohio State University Comprehensive Cancer Center

  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 INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: December 2, 2021
• Study Start: June 29, 2022
• Primary Completion (Estimated): June 15, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 3, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)