Clinical Trials /

Combination Chemotherapy and Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma

NCT02561273

Description:

This phase I/II trial studies the side effects and best dose of lenalidomide when given together with combination chemotherapy and to see how well they work in treating patients with newly diagnosed stage II-IV peripheral T-cell non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and etoposide, 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. Lenalidomide may stop the growth of peripheral T-cell non-Hodgkin's lymphoma by blocking the growth of new blood vessels necessary for cancer growth. Giving combination chemotherapy with lenalidomide may be a better treatment for peripheral T-cell non-Hodgkin's lymphoma.

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

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Combination Chemotherapy and Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma
  • Official Title: A Phase I/II Trial of CHOEP Chemotherapy Plus Lenalidomide as Front Line Therapy for Patients With Stage II, III and IV Peripheral T-Cell Non-Hodgkin's Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 511-14
  • SECONDARY ID: NCI-2015-00088
  • SECONDARY ID: RV-CL-PTCL-PI-003858
  • SECONDARY ID: 511-14
  • SECONDARY ID: P30CA036727
  • NCT ID: NCT02561273

Conditions

  • Anaplastic Large Cell Lymphoma, ALK-Negative
  • Anaplastic Large Cell Lymphoma, ALK-Positive
  • Hepatosplenic T-Cell Lymphoma
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
  • Stage II Angioimmunoblastic T-cell Lymphoma
  • Stage II Enteropathy-Associated T-Cell Lymphoma
  • Stage III Angioimmunoblastic T-cell Lymphoma
  • Stage III Enteropathy-Associated T-Cell Lymphoma
  • Stage IV Angioimmunoblastic T-cell Lymphoma
  • Stage IV Enteropathy-Associated T-Cell Lymphoma

Interventions

DrugSynonymsArms
Cyclophosphamide(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719Treatment (combination chemotherapy, lenalidomide)
Doxorubicin Hydrochloride5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, RubexTreatment (combination chemotherapy, lenalidomide)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213Treatment (combination chemotherapy, lenalidomide)
LenalidomideCC-5013, CC5013, CDC 501, RevlimidTreatment (combination chemotherapy, lenalidomide)
Prednisone.delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, Servisone, SK-PrednisoneTreatment (combination chemotherapy, lenalidomide)
Vincristine SulfateKyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfateTreatment (combination chemotherapy, lenalidomide)

Purpose

This phase I/II trial studies the side effects and best dose of lenalidomide when given together with combination chemotherapy and to see how well they work in treating patients with newly diagnosed stage II-IV peripheral T-cell non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and etoposide, 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. Lenalidomide may stop the growth of peripheral T-cell non-Hodgkin's lymphoma by blocking the growth of new blood vessels necessary for cancer growth. Giving combination chemotherapy with lenalidomide may be a better treatment for peripheral T-cell non-Hodgkin's lymphoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the safety and efficacy of lenalidomide in combination with standard induction
      therapy (CHOEP- cyclophosphamide, doxorubicin [doxorubicin hydrochloride], etoposide,
      vincristine [vincristine sulfate] and prednisone) in patients with newly diagnosed stage II,
      III and IV peripheral T-cell lymphoma not otherwise specified (NOS), anaplastic large cell
      lymphoma (anaplastic lymphoma receptor tyrosine kinase [ALK] negative) (ALK positive if
      International Prognostic Index [IPI] 3, 4, or 5), angioimmunoblastic T-cell lymphoma,
      enteropathy associated T-cell lymphoma or hepatosplenic gamma delta T-cell lymphoma.

      II. To establish the maximum tolerated dose of lenalidomide in combination with CHOEP
      chemotherapy. (Phase I) III. To assess the efficacy (complete response rate) of this
      combination. (Phase II)

      SECONDARY OBJECTIVES:

      I. To evaluate overall response rate (complete response [CR] + partial response [PR]) of the
      combination of lenalidomide and CHOEP chemotherapy.

      II. To evaluate the safety and tolerability of the regimen. III. To assess the 2 year
      progression free survival (PFS) and overall survival (OS) using this regimen.

      OUTLINE: This is a phase I, dose-escalation study of lenalidomide, followed by a phase II
      study.

      Patients receive cyclophosphamide intravenously (IV), doxorubicin hydrochloride IV and
      vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone
      orally (PO) on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days
      for 6 courses in the absence of disease progression or unacceptable toxicity. Patients
      responding after 6 courses of treatment may then undergo an autologous stem cell transplant
      or receive maintenance lenalidomide at the discretion of the physician or patient choice as
      follows:

      TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care.

      MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats
      every 28 days for up to 12 courses in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up every 3 months for 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (combination chemotherapy, lenalidomide)ExperimentalPatients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
  • Cyclophosphamide
  • Doxorubicin Hydrochloride
  • Etoposide
  • Lenalidomide
  • Prednisone
  • Vincristine Sulfate

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed new diagnosis of stage II, III and IV peripheral T-cell
             non-Hodgkin's lymphoma not otherwise specified (NOS), anaplastic large cell lymphoma
             (ALK negative) (ALK positive if IPI 3, 4, or 5), angioimmunoblastic T-cell lymphoma,
             enteropathy associated T-cell lymphoma, hepatosplenic gamma delta T-cell lymphoma

          -  Pathology material: hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC)
             slides or a representative formalin-fixed paraffin-embedded (FFPE) tissue block along
             with the pathology report from initial diagnosis, should be sent to be reviewed, and
             the diagnosis confirmed by Mayo Clinic department (retrospective diagnostic review:
             treatment may commence prior to the Mayo Clinic review)

          -  No prior therapy with the exception of prior radiation therapy and/or prednisone
             alone, at the discretion of the investigator based on current diagnosis and clinical
             condition; this prednisone treatment will not count toward the 6 cycles of treatment
             given in the study

          -  Expected survival duration of > 3 months

          -  Karnofsky performance status > 70

          -  Absolute neutrophil count (ANC) > 1000 cells/mm^3, unless cytopenias due to
             non-Hodgkin lymphoma (NHL) (i.e., bone marrow involvement or splenomegaly)

          -  Platelet count > 100,000/uL or > 75,000/uL if bone marrow (BM) involvement or
             splenomegaly

          -  Total bilirubin =< 1.5 x upper normal limit, or =< 3 x upper normal limit if
             documented hepatic involvement with lymphoma, or =< 5 x upper normal limit if history
             of Gilbert's disease

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper
             normal limit (=< 5 x upper normal limit if documented hepatic involvement with
             lymphoma)

          -  Serum creatinine < 2.0 mg/dL or calculated creatinine clearance (CrCl) > 45 mL/min
             (Cockcroft-Gault)

          -  Prothrombin time (PT) or international normalized ratio (INR), and partial
             thromboplastin time (PTT) =< 1.5 x upper limit of normal unless patient is receiving
             anticoagulants; if patient is on warfarin therapy, levels should be within therapeutic
             range

          -  If currently not on anticoagulation medication, willing and able to take aspirin (81
             or 325 mg) daily; if aspirin is contraindicated, the patient may be considered for the
             study if on therapeutic dose warfarin or low molecular weight heparin; patients unable
             to take any prophylaxis are not eligible

          -  Patients with measurable disease; patients with non-measurable but evaluable disease
             may be eligible after discussion with the principal investigator (PI); baseline
             measurements and evaluations must be obtained within 6 weeks of registration to the
             study; abnormal positron emission tomography (PET)/computed tomography (CT) scans will
             not constitute evaluable disease, unless verified by CT scan or other appropriate
             imaging

          -  Patients with measurable disease must have at least one objective measurable disease
             parameter; a clearly defined, bi-dimensionally measurable defect or mass measuring at
             least 1.5 cm in diameter on the CT portion of a PET/CT or CT scan or magnetic
             resonance imaging (MRI) (if appropriate) will constitute measurable disease; proof of
             lymphoma in the liver is required by a confirmation biopsy; skin lesions can be used
             as measurable disease provided bi-dimensional measurements are possible

          -  All study participants must be registered into the mandatory Revlimid Risk Evaluation
             and Mitigation Strategy (REMS) program, and be willing and able to comply with the
             requirements of the REMS program

          -  Women must not be pregnant or breast-feeding

               -  Females of reproductive potential must adhere to the scheduled pregnancy testing
                  as required in the Revlimid REMS program

               -  All females of childbearing potential must have a blood test within 2 weeks prior
                  to registration to rule out pregnancy

               -  Pregnancy testing is not required for post-menopausal or surgically sterilized
                  women

          -  Male and female patients of reproductive potential must agree follow accepted birth
             control measures

          -  Patient must be able to adhere to the study visit schedule and other protocol
             requirements

          -  Patients must be willing to give written informed consent, and sign an institutionally
             approved consent form before performance of any study-related procedure not part of
             normal medical care as noted above; with the exception of 1 cycle of chemotherapy
             based on current diagnosis and clinical condition, with the understanding that consent
             may be withdrawn by the subject at any time without prejudice to future medical care

          -  No serious disease or condition that, in the opinion of the investigator, would
             compromise the patient's ability to participate in the study

        Exclusion Criteria:

          -  Pregnant or breast feeding females

          -  Known seropositive for or active viral infection with human immunodeficiency virus
             (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are
             seropositive ( i.e. hepatitis B core antibody positive; quantitative deoxyribonucleic
             acid [DNA] negative) are eligible with appropriate prophylaxis

          -  Major surgery within 2 weeks of study drug administration

          -  Prior malignancies within the past 3 years with exception of adequately treated basal
             cell, squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix or
             breast; prostate cancer of Gleason grade 6 or less with stable prostate-specific
             antigen (PSA) levels

          -  Patients with a diagnosis of other peripheral T-cell lymphoma (PTCL) histologies other
             than those specified in the inclusion criteria

          -  Contraindication to any of the required concomitant drugs or supportive treatments,
             including hypersensitivity to all anticoagulation and antiplatelet options, or
             antiviral drugs

          -  Any other clinically significant medical disease or condition laboratory abnormality
             or psychiatric illness that, in the Investigator's opinion, may interfere with
             protocol adherence or a subject's ability to give informed consent

          -  Known hypersensitivity to thalidomide or lenalidomide

          -  The development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide, lenalidomide or similar drugs

          -  Ejection fraction of < 45% by either multi gated acquisition scan (MUGA) or
             echocardiogram (ECHO)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) of Lenalidomide and CHOEP
Time Frame:21 days
Safety Issue:
Description:MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I) within the first cycle of study treatment.

Secondary Outcome Measures

Measure:Number of Participants With Adverse Events Graded According to CTC (Phase II)
Time Frame:Up to 1 year
Safety Issue:
Description:The toxicity profile will be further assessed based on phase II patients. Overall toxicity incidence of maximum tolerated dose level of the Intent to treat (ITT) group of subjects is summarized. 39 subjects were dosed with 10 mg dose of Lenalidamide as the ITT group.
Measure:Overall Survival
Time Frame:Time from registration to death due to any cause, assessed up to 1 year
Safety Issue:
Description:The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Measure:Progression-free Survival
Time Frame:Time from registration to progression or death due to any cause, assessed up to 2 years
Safety Issue:
Description:The distribution of PFS will be estimated using the method of Kaplan-Meier. The PFS rate at 2 years will be estimated. A 2-year PFS rate of 60% will be considered of interest.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:University of Nebraska

Last Updated

June 18, 2021