T-Cell Large Granular Lymphocyte LeukemiaPhase 1/2NCT05141682
Oral Azacitidine for the Treatment of Relapsed or Refractory T-cell Large Granular Lymphocytic Leukemia
A Phase 1/2 study testing Oral Azacitidine in people with T-Cell Large Granular Lymphocyte Leukemia, run by Jonathan Brammer at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- T-Cell Large Granular Lymphocyte Leukemia
- What is being tested?
- Oral Azacitidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 Jun 2022to 30 Jan 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Virginia
Charlottesville, Virginia, 22908
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: A Phase I/II Clinical Trial Evaluating CC-486 in Patients With Relapsed/Refractory T-Cell Large Granular Lymphocytic Leukemia (T-LGLL)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the safety and maximum tolerated dose (MTD) of oral azacitidine (CC-486) in patients with symptomatic T-cell large granular lymphocytic leukemia (T-LGLL). (Phase I) II. To determine the overall response rate (complete response [CR] and partial response [PR]) of CC-486 in patients with T-LGLL. (Phase II)
SECONDARY OBJECTIVES:
- Duration of response to CC-486. II. Progression-free survival. III. Rate of conversion from PR at 4 months to CR at 8 and 12 months. IV. Rate of molecular remission (T-cell receptor [TCR] clearance, STAT3 mutation clearance) at 4, 8, 12 months.
- Effect of treatment on IL-15 promoter demethylation. VI. Effect of CC-486 on IL-15 promoter demethylation. VII. Safety of CC-486 in T-LGLL patients.
OUTLINE: This is a dose-escalation study.
Patients receive azacitidine orally (PO) on days 1-14. Treatment repeats every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with PR or CR continue treatment for up to 8 additional cycles in the absence of disease progression or unacceptable toxicity.
- Being tested
- Oral Azacitidine
- Medical subject headings
- Leukemia, Large Granular Lymphocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral AzacitidineDrug
Also called CC-486
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Oral Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of oral azacitidine (CC-486) (Phase I)
Measured: 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.
Measured: Up to 3 years
Secondary outcomes (9)
Duration of response to CC-486
Measured: Up to 3 years
Progression-free survival (PFS
Measured: Up to 3 years
Rate of conversion from PR at 4 months to CR at 8 months
Measured: From 4 months to 8 months
Rate of conversion from PR at 4 months to CR at 12 months
Measured: From 4 months to 12 months
Rate of molecular remission (T-cell receptor [TCR] clearance, STAT3 mutation clearance)
Measured: At 4 months
Rate of molecular remission (TCR clearance, STAT3 mutation clearance)
Measured: At 8 months
Rate of molecular remission (TCR clearance, STAT3 mutation clearance)
Measured: At 12 months
Rate of treatment-emergent adverse events
Measured: Up to 12 months
Degree of IL-15 promoter demethylation in responders versus non-responders
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2021
- Study start29 Jun 2022
- Primary completion19 Feb 2026
- Study completion30 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for T-Cell Large Granular Lymphocyte LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonathan Brammer
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Jonathan Brammer, Ohio State University Comprehensive Cancer Center
- Investigators
- Jonathan Brammer, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05141682
- Sponsor's protocol ID
- OSU-21018
- Other IDs
- NCI-2021-08491
- Status last verified
- Jul 2026
- First submitted
- 19 Nov 2021
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No