Efficacy and Safety of Oral Azacitidine Compared to Investigator's Choice Therapy in Patients With Relapsed or Refractory AITL

  • STATUS
    Recruiting
  • End date
    Dec 24, 2021
  • participants needed
    86
  • sponsor
    The Lymphoma Academic Research Organisation
Updated on 24 January 2021

Summary

This study evaluates the efficacy of Oral azacitidine versus single-agent Investigator's Choice Therapy in patients with Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma.

Description

Compared to B-cell Non-Hodgin Lymphoma (NHL), Angioimmunoblastic T-cell Lymphoma (AITL) is more resistant to conventional chemotherapy and is generally associated with an inferior outcome. In case of relapsed of refractory disease, survival durations are in the range of only a few months.

Several agents have been evaluated in this setting in recent years: romidepsin, bendamustine or belinostat. The response rate with these agents rarely exceeds 30% and responses are usually of limited duration.

Azacitidine is a nucleoside metabolic inhibitor indicated for the treatment of patients with various myelodysplastic syndrome (MDS) subtypes. In this case, azacitidine significantly increase the survival time compared to standard of care option. This response to azacitidine could be correlated to the existence of recurrent mutations and those mutations have also been described in AITL.

The present protocol will use Azacitidine according to the same schedule than in MDS that is continuous treatment until progression or unacceptable toxicity.

Details
Condition Relapsed Angioimmunoblastic T-Cell Lymphoma, Refractory Angioimmunoblastic T-cell Lymphoma, Relapsed Angioimmunoblastic T-Cell Lymphoma, Refractory Angioimmunoblastic T-cell Lymphoma, Relapsed Angioimmunoblastic T-Cell Lymphoma, Refractory Angioimmunoblastic T-cell Lymphoma, Relapsed Angioimmunoblastic T-Cell Lymphoma, Refractory Angioimmunoblastic T-cell Lymphoma, Relapsed Angioimmunoblastic T-Cell Lymphoma, Refractory Angioimmunoblastic T-cell Lymphoma, Relapsed Angioimmunoblastic T-Cell Lymphoma, Refractory Angioimmunoblastic T-cell Lymphoma
Treatment Gemcitabine, romidepsin, Bendamustine, Oral Azacitidine
Clinical Study IdentifierNCT03593018
SponsorThe Lymphoma Academic Research Organisation
Last Modified on24 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Relapsed Angioimmunoblastic T-Cell Lymphoma or Refractory Angioimmunoblastic T-cell Lymphoma?
Patients must satisfy all following criteria to be enrolled in the study
Patient is 18 years of age at the time of signing the informed consent form (ICF)
Patient must understand and voluntarily sign an ICF prior to any study-specific assessments/procedures being conducted
Patient is willing and able to adhere to the study visit schedule and other protocol requirements
Patient had local diagnosed peripheral T cell lymphoma (PTCL) with T-follicular helper (TFH) phenotype according to the criteria of the latest World Health Organization (WHO) classification based on a surgical lymph node biopsy including any one of
Angioimmunoblastic T cell lymphoma (AITL)
Follicular T cell lymphoma
Nodal peripheral T-cell lymphoma with TFH phenotype There should be a documented expression of minimum two TFH markers among this panel of markers : CD10, CXCL13, PD1, ICOS and BCL6 by the tumoral cells by immunohistochemistry. Biopsy at relapse or progression is not mandatory, but highly encouraged on a surgical or needle core biopsy, and diagnostic tissue should be available for central pathology review and for ancillary molecular studies
Local pathology report should be reviewed by the sponsor's medical monitor
prior to enrollment
\. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3
\. Relapsed (after partial or complete response) or refractory AITL after at
least one line of systemic therapy (there is no mandatory resting period after
the previous treatment as long as the biochemistry and hematology labs meet
the inclusion criteria as below.)
\. Meet the following lab criteria
Absolute Neutrophil Count (ANC) 1,5 x 109/L ( 1 x 109/L if bone marrow (BM) involvement by lymphoma)
Platelet 75 x 109/L ( 50 x 109/L if BM involvement by lymphoma)
Hemoglobin 8 g/dL. 8. Anticipated life expectancy at least 3 months 9. At least one measurable lesion on CT that is greater than 1.5 cm in the longest diameter for nodal lesions and greater than 1.0 cm in the longest diameter for extranodal lesions. The lesion must be measurable in two perpendicular dimensions. Patients with only cutaneous disease will be excluded. 10. Female patient of childbearing potential (FCBP) may participate, providing she meets the following conditions
Have two negative pregnancy tests as verified by the investigator prior to
starting study treatment: serum pregnancy test at Screening and negative serum
or urine pregnancy test (investigator's discretion) within 72 hours prior to
starting treatment with study treatment (Cycle 1 Day 1). She must agree to
ongoing pregnancy testing during the study (before beginning each subsequent
cycle of treatment), and 28 days after the last study drug administration
This applies even if the patient practices complete abstinence from
heterosexual contact
Agrees to practice true abstinence (which must be reviewed monthly and source
documented) or agrees to the use of highly effective methods of contraception
from 28 days prior to starting study treatment, and must agree to continue
using such precautions during study treatment (including dose interruptions)
and for up to 90 days after the last study drug administration. True
abstinence is acceptable when this is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation
symptom-thermal, post ovulation methods) and withdrawal are not acceptable
methods of contraception. Cessation of contraception after this point should
be discussed with a responsible physician
Agrees to abstain from breastfeeding during study participation and for at
least 90 days after the last study drug administration
A female of childbearing potential (FCBP) is a female who: 1) has achieved
menarche at some point, 2) has not undergone a hysterectomy or bilateral
oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following
cancer therapy does not rule out childbearing potential) for at least 24
consecutive months (i.e., has had menses at any time during the preceding 24
consecutive months)
\. Male patient must either practice true abstinence from heterosexual
contact (which must be reviewed on a monthly basis and source documented) or
agrees to avoid fathering a child, to use highly effective methods of
contraception, male condom plus spermicide during sexual contact with a
pregnant female or a female of childbearing potential (even if he has
undergone a successful vasectomy), from starting dose of drug (cycle 1 Day 1)
including dose interruptions through 90 days after receipt of the last study
drug administration. Furthermore, male patient must agree to not give semen or
sperm during study drug therapy and for a period of 1 year after end of study
drug therapy
\. For EU countries, patient covered by a social security system

Exclusion Criteria

Presence of any of the following will exclude a patient from enrollment
Clinical evidence of central nervous system involvement by lymphoma. Patients with suspicion of central nervous system (CNS) involvement must undergo neurologic evaluation and CT/MRI of head and lumbar puncture to exclude CNS disease
Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator's decision)
Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
Known Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV) infection, or evidence of positive HTLV1 serology or of active Hepatitis B (HB) Virus (HBV) infection defined as
HB s Ag positive
HB s Ag negative, anti-HB s antibody positive and/or anti-HB c antibody positive with detectable viral DNA
Impaired renal function (MDRD formula or Cockcroft-Gault Creatinine Clearance < 30 ml/min) or impaired liver function tests (Serum total bilirubin level > 2.0 mg/dl [34 mol/L] (except in case of Gilbert's Syndrome, or documented liver or pancreatic involvement by lymphoma), Serum transaminases (AST or ALT) > 3 upper normal limits) unless they are related to the lymphoma
Active malignancy other than the one treated in this research. Prior history of malignancies, other than low risk MDS or chronic myelomonocytic leukemia (CMML) (with less than 5% blasts in bone marrow), unless the patient has been free of the disease for 3 years. However, patients with the following history/concurrent conditions are
allowed
Basal or squamous cell carcinoma of the skin
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor-nodes-metastasis (TNM)] clinical staging system
Early-stage gastric cancer suitable for endoscopic mucosal resection or endoscopic submucosal dissection
Treatment with any investigational drug within 5 half-lives before planned first cycle of study treatment and during the study. Ongoing medically significant adverse events from previous treatment, regardless of the time period
Prior exposure to azacitidine and/ or any other demethylating agent (eg, decitabine)
Prior exposure to planned study treatment investigator's choice therapy (eg, prior exposure to gemcitabine is an exclusion if gemcitabine is the investigator's choice therapy prior to randomization)
Concurrent use of corticosteroids unless the patient is on a stable or decreasing dose for 1 week prior to informed consent form signature
Knowing or suspected hypersensitivity to active substance or to any of the excipients
Pregnant, planning to become pregnant, or lactating woman
Candidate for hematopoietic stem cell transplantation
History of active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the oral azacitidine and/or predispose the patient to an increased risk of gastrointestinal toxicity per investigator's decision. Any condition causing inability to swallow tablets
Significant active cardiac disease within the previous 6 months, including
New York Heart Association (NYHA) class IV congestive heart failure
Unstable angina or angina requiring surgical or medical intervention; and/or
Myocardial infarction
Person deprived of his/her liberty by a judicial or administrative decision
Adult person under legal protection
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