Clinical Trials /

Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma

NCT02232516

Description:

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).

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-Cell Lymphoma
  • Enteropathy-Associated T-Cell Lymphoma
  • Mycosis Fungoides
  • Peripheral T-Cell Lymphoma
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma
  • Official Title: Phase II Study of Romidepsin Plus Lenalidomide for Patients With Previously Untreated PTCL

Clinical Trial IDs

  • ORG STUDY ID: NU 14H04
  • SECONDARY ID: NCI-2014-01770
  • SECONDARY ID: RV-CL-PTCL-PI-003974
  • SECONDARY ID: STU00097620
  • SECONDARY ID: P30CA060553
  • NCT ID: NCT02232516

Conditions

  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Hepatosplenic T-cell Lymphoma
  • Peripheral T-cell Lymphoma
  • Stage I Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage IA Mycosis Fungoides/Sezary Syndrome
  • Stage IB Mycosis Fungoides/Sezary Syndrome
  • Stage II Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage IIA Mycosis Fungoides/Sezary Syndrome
  • Stage IIB Mycosis Fungoides/Sezary Syndrome
  • Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage IIIA Mycosis Fungoides/Sezary Syndrome
  • Stage IIIB Mycosis Fungoides/Sezary Syndrome
  • Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage IVA Mycosis Fungoides/Sezary Syndrome
  • Stage IVB Mycosis Fungoides/Sezary Syndrome

Interventions

DrugSynonymsArms
romidepsinFK228, FR901228, IstodaxTreatment (romidepsin, lenalidomide)
lenalidomideCC-5013, IMiD-1, RevlimidTreatment (romidepsin, lenalidomide)

Purpose

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).

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (romidepsin, lenalidomide)ExperimentalPatients receive romidepsin IV over 4 hours on days 1, 8, and 15 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
  • romidepsin
  • lenalidomide

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR), as defined per Cheson criteria
Time Frame:Assessed after cycles 3 and 6, then every 6 months up to 3 years
Safety Issue:
Description:ORR will be assessed by imaging after cycles 3 and 6, and then every 6 months up to 3 years.

Secondary Outcome Measures

Measure:Incidence of toxicity assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Evaluated once per cycle (1 cycle=28 days) up to 1 year
Safety Issue:
Description:The frequency and severity of toxicity events will be evaluated. All adverse events will be summarized as to type, severity, frequency, timing and attribution.
Measure:Progression-free survival (PFS)
Time Frame:Reported at 1 and 3 years after the start of treatment
Safety Issue:
Description:PFS will be evaluated at 1 and 3 years after treatment has begun.
Measure:Overall survival (OS)
Time Frame:Reported at 1 and 3 years after the start of treatment
Safety Issue:
Description:OS will be assessed at 1 and 3 years after treatment has begun.
Measure:Duration of response, defined per Cheson criteria
Time Frame:Assessed from start of therapy for up to 3 years
Safety Issue:
Description:The duration of overall response is measured from the time measurement criteria are met for Complete Remission or Partial Response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.
Measure:Delay to cytotoxic chemotherapy
Time Frame:Up to 1 year
Safety Issue:
Description:Time to first cytotoxic chemotherapy is defined as the time (in months) from start of study treatment to time of first dose of anti-neoplastic cytotoxic chemotherapy that is administered to treat lymphoma.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Northwestern University

Last Updated

February 17, 2020