Trial Title:
Study of Tazemetostat in Lymphoid Malignancies
NCT ID:
NCT05983965
Condition:
T-cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Conditions: Keywords:
T-cell Lymphoma
Leukemia
Lymphoma
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tazemetostat
Description:
Treatment: On day 1 and day 15 of the first cycle, and day 1 of all following cycles, the
subject will have office visit with physical exam, vital signs, and lab tests. The
subject will take tazemetostat twice a day by mouth continuously as an outpatient. If
continuing on the treatment for more than 6 cycles, visits change to every 3 months.
Arm group label:
Cohort A
Summary:
Tazemetostat is an oral EZH2 inhibitor which has been FDA approved for adult patients
with relapsed or refractory (R/R) follicular lymphoma (FL) whose tumors are positive for
an EZH2 mutation as detected by an FDA-approved test and who have received at least 2
prior systemic therapies, and for adult patients with R/R FL who have no satisfactory
alternative treatment option. We propose a study to evaluate the safety of tazemetostat
in relapsed / refractory peripheral T-cell lymphoma.
Criteria for eligibility:
Criteria:
Inclusion criteria
1. Histologically confirmed peripheral T-cell lymphomas (PTCL) with allowed subtypes
listed below as per the revised World Health Organization 2022 classification [6]:
PTCL subtypes allowed
1. PTCL-not otherwise specified (NOS)
2. Nodal T-follicular helper cell lymphoma - angioimmunoblastic type, follicular
type, or NOS
3. Anaplastic Large Cell Lymphoma (ALK+)
4. Anaplastic Large Cell Lymphoma (ALK-)
5. Enteropathy-associated T-cell lymphoma
6. Monomorphic epitheliotropic intestinal T-cell lymphoma
7. Hepatosplenic T-cell lymphoma
8. Subcutaneous panniculitis-like T-cell lymphoma
9. Adult T-cell leukemia / lymphoma - lymphomatous, acute, or unfavorable chronic
subtypes
2. Patients must have relapsed or refractory disease.
1. Relapsed disease is defined when a patient progressed (>3 months) after
achieving CR with a previous treatment
2. Refractory disease is defined when a patient failed to achieve a CR or PR after
a previous treatment
3. Patients received at least 1 prior therapy for PTCL.
4. At least one bi-dimensionally measurable nodal lesion, defined as ≥ 1.5 cm in its
longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as
≥ 1.0 cm in its longest diameter on fluorodeoxyglucose (FDG) positron emission
tomography (PET)/computed tomography (CT) scan as defined by response criteria for
PTCL
5. Age ≥ 18.
6. Patients with Hepatitis C can be included if they have completed therapy for
hepatitis C with undetectable viral load.
7. Patients with Hepatitis B can be included if they are on suppressive therapy for
hepatitis B infection and with no detectable viral load.
8. Patients with HIV can be included if they are on appropriate antiretroviral therapy,
there is no interaction with the study drug, a CD4+ T-cell counts ≥ 350 cells/µL and
no detectable viral load.
9. Adequate organ function as defined below unless attributed to disease involvement
(Note: transfusions and growth factors allowed during screening; however,
transfusion-dependency defined as requiring blood products ≥once per week not
allowed):
i. Liver function: No more than moderate hepatic impairment per NCI ODWG criteria -
Total bilirubin ≤ 3X upper limit of normal (ULN), AST ≤ ULN (unless attributed to
fatty liver or disease involvement).
ii. Kidney function: CrCl > 30ml/min using Cockroft-Gault, based on actual weight.
iii. ANC ≥ 1,000/µL, Platelet Count ≥ 75,000/ µL, Hemoglobin ≥ 8.0 g/dl.
10. Left ventricular ejection fraction (LVEF) defined by multiple-gated acquisition
(MUGA) scan or echocardiogram within the institutional limits of normal.
11. Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2.
12. A negative urine or serum pregnancy test is required for all women of childbearing
potential within 1 week prior to enrolling on this trial and within 3 days of first
dose of study drug. Note: Urine pregnancy tests that cannot be confirmed as negative
require a confirmatory negative serum pregnancy test.
Non-childbearing potential is defined as:
- Postmenopausal: Defined as no menses for 12 months without an alternative
medical cause. A high follicle-stimulating hormone (FSH) level in the
postmenopausal range may be used to confirm post-menopausal state in women not
using hormonal contraception or hormonal replacement therapy. In the absence of
12 months of amenorrhea, FSH measurements indicating post-menopausal status
must be documented in patient's medical history.
- Permanently sterile: Documented permanent sterilization e.g., hysterectomy,
bilateral salpingectomy and bilateral oophorectomy.
13. If female of childbearing potential, subject must not be pregnant or be
breastfeeding and is required to have a negative urine or serum pregnancy test
within 3 days prior to the first dose of study drug. In addition, females of
childbearing potential must either practice complete abstinence or agree to use two
effective methods of contraception simultaneously, beginning ≥ 28 days prior to
start of tazemetostat, during tazemetostat treatment, and for at least 6 months
after final dose of tazemetostat. See Appendix E regarding contraception guidelines.
14. Male subjects must either practice complete abstinence or agree to use a latex or
synthetic condom during any sexual contact with a female of childbearing potential,
from first dose of tazemetostat, during study treatment including dose
interruptions, and for 3 months after last dose of tazemetostat. This applies even
to males who have undergone successful vasectomy with medically confirmed
azoospermia.
15. Willing and able to participate in all required evaluations and procedures in this
study protocol including receiving intravenous administration of investigational
product and being admitted, when required, for at least 24 hours during
investigational product administration.
Exclusion criteria
1. Current evidence of central nervous system involvement.
2. Completion of an autologous hematopoietic stem cell transplantation within 3 months
prior to first dose of study drug.
3. Prior allogeneic stem cell transplant within 6 months. The patient should not have
any active GVH or should be on immune suppressive agents.
4. Completion of treatment with any radiotherapy, chemotherapy, antibody,
immunoconjugates and/or another investigational drug ≤4 weeks (or 5 half-lives of
the drug, whichever is shorter) prior to first dose of study drug. Patients may be
enrolled after a minimum of 2 weeks of radiation if radiation was for palliative
intent.
5. Prior therapy with an EZH2 inhibitor.
6. Inability to swallow and retain oral medications.
7. Pregnant women are excluded from this study.
8. Any active, concurrent, significant illness or disease (other underlying lymphoma)
or clinically significant findings including psychiatric and behavioral problems,
medical history and/or physical examination findings that would preclude the patient
from participation in the study such as:
i. Active infection requiring systemic therapy ≤10 days before the first dose of
study drug; ii. Unstable angina pectoris, symptomatic congestive heart failure (New
York Heart Association [NYHA] II, III, IV;), myocardial infarction ≤6 months prior
to first study drug, uncontrolled cardiac arrhythmia e.g., atrial
fibrillation/flutter, cerebrovascular accidents ≤6 months before first dose of study
drug; iii. Any severe or uncontrolled other disease or condition which might
increase the risk associated with study participation.
9. Vaccination with live, attenuated vaccines within 28 days prior to the first dose of
study medication.
10. Receiving systemic immunosuppressive medications (including, but not limited to,
cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
factor agents). The use of inhaled corticosteroids is permitted.
11. Corticosteroids ≥ 10 mg of prednisone within the last 7 days.
12. Has had a solid organ transplant within the last 3 years. Note: Patients who have
had a solid organ transplant >3 years ago are eligible if there are no
signs/symptoms of graft versus host disease (GvHD) and off immunosuppressive
medications as per above.
13. Any prior history of myeloid malignancies, including myelodysplastic syndrome
(MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN).
14. Any prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute
lymphoblastic leukemia (T-ALL).
15. Patients with the following subtypes of lymphoma:
i. T-cell prolymphocytic leukemia ii. T-large granular lymphocytic leukemia iii.
NK-large granular lymphocytic leukemia iv. Aggressive NK-cell leukemia v. Breast
implant-associated anaplastic large-cell lymphoma
16. Any other malignancy known to be active, with the exception of i. Cervical carcinoma
of Stage 1B or less ii. Non-invasive basal cell or squamous cell skin carcinoma iii.
Non-invasive, superficial bladder cancer iv. Prostate cancer with a current PSA
level < 0.1 ng/mL v. Any curable or localized cancer with a CR of > 2 years'
duration.
17. Any malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg,
nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat.
18. Major surgery within 4 weeks before the first dose of study intervention. Note:
Minor surgery (eg, minor biopsy of extracranial site, central venous catheter
placement, shunt revision) is permitted within 3 weeks prior to enrolment.
Gender:
All
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Alabama at Birmingham
Address:
City:
Birmingham
Zip:
35294
Country:
United States
Status:
Recruiting
Contact:
Last name:
Margaret A Thomas
Email:
margaretannthomas@uabmc.edu
Contact backup:
Last name:
Lauren Shea, MD
Contact backup:
Last name:
Mayur Narkhede, MD
Contact backup:
Last name:
Amitkumar Mehta, MD
Start date:
September 5, 2024
Completion date:
December 2029
Lead sponsor:
Agency:
University of Alabama at Birmingham
Agency class:
Other
Source:
University of Alabama at Birmingham
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05983965
