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

  • End date
    Dec 31, 2025
  • participants needed
  • sponsor
    Jonathan Brammer
Updated on 12 May 2022


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.



I. 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)


I. 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.

V. 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.

Condition T-Cell Large Granular Lymphocyte Leukemia
Treatment Oral Azacitidine
Clinical Study IdentifierNCT05141682
SponsorJonathan Brammer
Last Modified on12 May 2022


Yes No Not Sure

Inclusion Criteria

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). 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

Exclusion Criteria

Absolute neutrophil count (ANC) less than 200/m
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note