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, NOS
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 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
CyclophosphamideTreatment (combination chemotherapy, lenalidomide)
Doxorubicin HydrochlorideTreatment (combination chemotherapy, lenalidomide)
Vincristine SulfateKyocristine, Oncovin, VCR, VincasarTreatment (combination chemotherapy, lenalidomide)
EtoposideLastetTreatment (combination chemotherapy, lenalidomide)
PrednisoneTreatment (combination chemotherapy, lenalidomide)
LenalidomideCC-5013, CC5013, CDC 501, IMiD-1Treatment (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
  • Vincristine Sulfate
  • Etoposide
  • Prednisone
  • Lenalidomide

    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, (as well as 8 unstained slides of 4 micron thickness to store for future IHC and deoxyribonucleic acid [DNA] studies), 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); please NOTE: the diagnostic H&E slide and IHC slides will be returned after review; only the 8 unstained slides will be retained/stored for future use

    - No prior therapy with the exception of prior radiation therapy and/or 1 cycle of chemotherapy (may be any chemotherapy regimen or even prednisone alone) based on current diagnosis and clinical condition; this cycle of 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 mm^3 or > 75 mm^3 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) scans will not constitute evaluable disease, unless verified by computed tomography (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 a CT scan 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 because of hepatitis B virus vaccine are eligible

    - 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 of lenalidomide and CHOEP, 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)
    Time Frame:21 days
    Safety Issue:
    Description:Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

    Secondary Outcome Measures

    Measure:Incidence of toxicity 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 as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
    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.
    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.

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University of Nebraska

    Trial Keywords

      Last Updated

      October 30, 2016