The purpose of this study is to evaluate how safe and effective the combination of the study
drugs romidepsin and lenalidomide is for treating patients with peripheral t-cell lymphoma
(PTCL) who have not been previously treated for this cancer. Currently, there is no standard
treatment for patients with PTCL; the most common treatment used is a combination of drugs
called CHOP, but this can be a difficult treatment to tolerate because of side effects, and
is not particularly effective for most patients with PTCL. Romidepsin (Istodax®) is a type of
drug called an HDAC inhibitor. It interacts with DNA (genetic material in cells) in ways that
can stop tumors from growing. It is given as an infusion through the veins. Lenalidomide
(Revlimid®) is a type of drug known as an immunomodulatory drug, or IMID for short. This drug
affects how tumor cells grow and survive, including affecting blood vessel growth in tumors.
It is given as an oral tablet (by mouth).
PRIMARY OBJECTIVES:
I. To evaluate the efficacy of the combination of romidepsin plus lenalidomide in patients
with previously untreated peripheral T-cell lymphoma (PTCL).
SECONDARY OBJECTIVES:
I. Evaluate the safety of the combination of romidepsin and lenalidomide. II. Further
evaluate efficacy of the combination of romidepsin and lenalidomide.
III. Evaluate the delay to cytotoxic chemotherapy.
TERTIARY OBJECTIVES:
I. Evaluate the use of Northwestern Medicine (NM) positron emission tomography (PET)/computed
tomography (CT) vs CT imaging in PTCL.
II. Validate a new prognostic model for newly diagnosed PTCL. III. Investigate the tumor
immunohistochemical profile to identify potential biomarkers associated with prognosis and
treatment response.
OUTLINE:
Patients receive romidepsin intravenously (IV) over 4 hours on days 1, 8, and 15 and
lenalidomide orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 days for up
to 1 year in the absence of disease progression, inter-current illness that prevents further
administration of treatment, unacceptable toxicity, patient decides to withdraw from study
treatment (or study as a whole), or general or specific changes in the patient's condition
render the patient unacceptable for further treatment in the judgment of the treating
investigator.
After completion of study treatment, patients are followed up every 3 months for 1 year and
then every 6 months for 3 years.
Inclusion Criteria:
- Histologically confirmed diagnosis of PTCL (using the most recent edition of the World
Health Organization [WHO] Classification of Tumors of Hematopoietic and Lymphoid
Tissues as guidance) including:
- Anaplastic large cell lymphoma, anaplastic large cell kinase (ALK)-negative
- Angioimmunoblastic T-cell lymphoma
- Enteropathy-type T-cell lymphoma
- Extranodal natural killer (NK)/T-cell lymphoma, nasal type
- Hepatosplenic gamma-delta T-cell lymphoma
- Peripheral T-cell lymphoma, unspecified (not otherwise specified [NOS])
- Transformed mycosis fungoides
- Subcutaneous panniculitis-like T-cell lymphoma.
- NOTE: A copy of the pathology report is sufficient to register the patient to the
trial; diagnosis of PTCL should have been based on identification in biopsy
specimens of a peripheral T-cell lymphoma disorder characterized by positivity in
the malignant cell population of at least 3 of the following T-cell markers:
betaF1, cluster of differentiation (CD)2, CD3, CD4, CD5, CD7, CD8, and negativity
of at least 2 of the following B-cell markers CD19, CD20, CD79alpha and paired
box 5 (Pax-5); further, CD56 should be used for the diagnosis of the nasal type,
while CD30, ALK-1 and Pax-5 (that should be negative) are required for the
anaplastic type; CD10, chemokine (C-X-C motif) ligand 13 (CXCL13), programmed
cell death (PD)-1 and CD21 are warranted for the diagnosis of angioimmunoblastic
T-cell lymphoma along with Epstein-Barr virus-encoded small ribonucleic acid
(RNA) (EBER) in situ hybridization; determination of mindbomb E3 ubiquitin
protein ligase 1(Mib-1)/marker of proliferation Ki-67 (Ki-67) to be performed;
finally, additional markers useful within the context of anaplastic large cell
lymphoma, extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell
lymphoma are TIA1 cytotoxic granule-associated RNA binding protein (TIA-1),
granzyme B and perforin; it is acknowledged that no marker has absolute lineage
specificity, and that immunophenotypic studies should be performed with panels of
monoclonal antibodies; final diagnoses containing caveats such as "suspicious of"
or "presumably" are considered inadequate for a patient to be enrolled in the
trial
- NOTE: Patients with adequate archived (well-preserved, formalin-fixed) biopsy
tissue remaining will be required to submit a portion for exploratory studies;
this is not optional if tissue is available; however, lack of adequate tissue for
exploratory studies will not preclude patients from participating
- Patients must have bi-dimensionally measurable disease (>= 1 cm) by CT imaging
- NOTE: Patients with marrow-only disease are eligible; response for these patients
will be assessed by repeat bone marrow biopsy
- Patients must fit into one of the following categories:
- Age >= 18 years to < 60 years with a cumulative illness rating scale (CIRS) score
>= 6 OR deemed ineligible for cytotoxic chemotherapy by the treating investigator
- >= 60 years
- Patients must have adequate organ and marrow function (documented within 14 days prior
to registration) as outlined below:
- Absolute neutrophil count (ANC) >= 750/mcl
- Hemoglobin >= 8 g/dl
- Platelets >= 50,000/mcl
- Total bilirubin =< 2 x upper limit normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
and alanine aminotransferase (ALT) (serum pyruvate glutamate transaminase [SPGT])
=< 3 x ULN
- Creatinine =< 2 x ULN
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =<
2
- All patients must agree to use effective contraception while on study, and all
patients must agree to undergo counseling sessions every 28 days about pregnancy
precautions and risks of fetal exposure
- Females of childbearing potential (FCBP) must either commit to continued
abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
control: one highly effective method and one additional effective method AT THE
SAME TIME, at least 28 days before starting lenalidomide, during lenalidomide
therapy, during dose interruptions, and for at least 28 days following
discontinuation of lenalidomide therapy
- Males receiving lenalidomide must agree to use a latex condom during any sexual
contact with FCBPs even if they have undergone a successful vasectomy
- NOTE: A FCBP is any woman (regardless of sexual orientation, having undergone a
tubal ligation, or remaining celibate by choice) who meets the following
criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy
- Has not been naturally postmenopausal for at least 12 consecutive months
(i.e., has had menses at any time in the preceding 12 consecutive months)
- FCBP should be referred to a qualified provider of contraceptive methods, if
needed
- FCPB must have a negative urine or serum pregnancy test within 7 days prior to
registration, and be willing to adhere to the scheduled pregnancy testing as required
in the Revlimid Risk Evaluation and Mitigation Strategies (REMS®) program
- NOTE: Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately
- Patients must be free of any prior malignancies for >= 1 year
- NOTE: The exception to this would be currently treated squamous cell and basal
cell carcinoma of the skin, carcinoma in situ of the cervix, breast, or bladder,
or surgically removed melanoma in situ of the skin (stage 0) with histologically
confirmed free margins of excision
- All study participants must be registered into the mandatory Revlimid REMS® program,
and be willing and able to comply with the requirements of the REMS® program
- Patients must have the ability to understand and the willingness to sign a written
informed consent prior to registration
Exclusion Criteria:
- Patients with a diagnosis of any of the following are not eligible:
- Anaplastic large cell lymphoma, ALK-positive
- Adult T-cell lymphoma/leukemia (ATLL)
- Anaplastic large-cell lymphoma, primary cutaneous type
- Precursor T-lymphoblastic lymphoma/leukemia
- Mycosis fungoides/Sezary syndrome (except transformed Mycosis fungoides [MF])
- NK-cell leukemia
- T-cell granular lymphocytic leukemia
- T-cell prolymphocytic leukemia
- Patients must not have received prior systemic therapy for PTCL (except for
corticosteroids for 10 or fewer days at any dose, no washout period required as long
as they discontinue prior to starting study therapy); NOTE: topical treatment may have
been given for prior existence of cutaneous lymphoma that has since become systemic
PTCL; however, these topical therapies should be stopped at time of registration
- Patients who received chemotherapy (including monoclonal antibodies) or radiotherapy,
administered for any condition, within 4 weeks prior to registration are not eligible
- Patients who received prior exposure to any other histone deacetylase (HDAC)
inhibitors or immunomodulatory (IMID) agents for any reason are not eligible
- Patients receiving ongoing treatment with any other investigational agents are not
eligible
- Patients who have known central nervous system (CNS) involvement of lymphoma are not
eligible
- Patients who have an uncontrolled intercurrent illness including, but not limited to,
any of the following are not eligible:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study
requirements
- Patients with a known human immunodeficiency (HIV) infection are not eligible
- Patients who are pregnant or actively nursing an infant are not eligible
- Patients with a QT interval > 500 msec (using the Bazett's formula) within 28 days
prior to registration are not eligible
