Clinical Trials /

Lenalidomide Maintenance Therapy After High Dose BEAM With or Without Rituximab

NCT01035463

Description:

This phase I/II trial studies the side effects and best dose of lenalidomide when given after combination chemotherapy with or without rituximab and stem cell transplant and to see how well it works in treating patients with persistent or recurrent non-Hodgkin lymphoma that is resistant to chemotherapy. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as carmustine, etoposide, cytarabine, and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Lenalidomide</span> as Maintenance Therapy After Combination <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> With or Without <span class="go-doc-concept go-doc-intervention">Rituximab</span> and <span class="go-doc-concept go-doc-intervention">Stem Cell Transplant</span> in Treating Patients With Persistent or Recurrent <span class="go-doc-concept go-doc-disease">Non-Hodgkin Lymphoma</span> That is Resistant to <span class="go-doc-concept go-doc-intervention">Chemotherapy</span>

Title

  • Brief Title: Lenalidomide as Maintenance Therapy After Combination Chemotherapy With or Without Rituximab and Stem Cell Transplant in Treating Patients With Persistent or Recurrent Non-Hodgkin Lymphoma That is Resistant to Chemotherapy
  • Official Title: Phase I/II Study of Lenalidomide Maintenance Following BEAM (+/- Rituximab) for Chemo-Resistant or High Risk Non-Hodgkin's Lymphoma
  • Clinical Trial IDs

    NCT ID: NCT01035463

    ORG ID: 446-08

    NCI ID: NCI-2009-01436

    Trial Conditions

    Adult Nasal Type Extranodal NK/T-cell Lymphoma

    Anaplastic Large Cell Lymphoma

    Angioimmunoblastic T-cell Lymphoma

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue

    Nodal Marginal Zone B-cell Lymphoma

    Peripheral T-cell Lymphoma

    Recurrent Adult Burkitt Lymphoma

    Recurrent Adult Diffuse Large Cell Lymphoma

    Recurrent Adult Diffuse Mixed Cell Lymphoma

    Recurrent Adult Diffuse Small Cleaved Cell Lymphoma

    Recurrent Adult Grade III Lymphomatoid Granulomatosis

    Recurrent Adult Immunoblastic Large Cell Lymphoma

    Recurrent Adult Lymphoblastic Lymphoma

    Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma

    Recurrent Grade 1 Follicular Lymphoma

    Recurrent Grade 2 Follicular Lymphoma

    Recurrent Grade 3 Follicular Lymphoma

    Recurrent Mantle Cell Lymphoma

    Recurrent Marginal Zone Lymphoma

    Recurrent Mycosis Fungoides/Sezary Syndrome

    Recurrent Small Lymphocytic Lymphoma

    Splenic Marginal Zone Lymphoma

    Stage III Adult Burkitt Lymphoma

    Stage III Adult Diffuse Large Cell Lymphoma

    Stage III Adult Diffuse Mixed Cell Lymphoma

    Stage III Adult Diffuse Small Cleaved Cell Lymphoma

    Stage III Adult Immunoblastic Large Cell Lymphoma

    Stage III Adult Lymphoblastic Lymphoma

    Stage III Cutaneous T-cell Non-Hodgkin Lymphoma

    Stage III Grade 1 Follicular Lymphoma

    Stage III Grade 2 Follicular Lymphoma

    Stage III Grade 3 Follicular Lymphoma

    Stage III Mantle Cell Lymphoma

    Stage III Marginal Zone Lymphoma

    Stage III Mycosis Fungoides/Sezary Syndrome

    Stage III Small Lymphocytic Lymphoma

    Stage IV Adult Burkitt Lymphoma

    Stage IV Adult Diffuse Large Cell Lymphoma

    Stage IV Adult Diffuse Mixed Cell Lymphoma

    Stage IV Adult Diffuse Small Cleaved Cell Lymphoma

    Stage IV Adult Immunoblastic Large Cell Lymphoma

    Stage IV Adult Lymphoblastic Lymphoma

    Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma

    Stage IV Grade 1 Follicular Lymphoma

    Stage IV Grade 2 Follicular Lymphoma

    Stage IV Grade 3 Follicular Lymphoma

    Stage IV Mantle Cell Lymphoma

    Stage IV Marginal Zone Lymphoma

    Stage IV Mycosis Fungoides/Sezary Syndrome

    Stage IV Small Lymphocytic Lymphoma

    Waldenstrm Macroglobulinemia

    Trial Interventions

    Drug Synonyms Arms
    lenalidomide CC-5013, IMiD-1, Revlimid Treatment (stem cell transplantation)
    carmustine BCNU, BiCNU, bis-chloronitrosourea Treatment (stem cell transplantation)
    etoposide EPEG, VP-16, VP-16-213 Treatment (stem cell transplantation)
    cytarabine ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside Treatment (stem cell transplantation)
    melphalan Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin Treatment (stem cell transplantation)

    Trial Purpose

    This phase I/II trial studies the side effects and best dose of lenalidomide when given
    after combination chemotherapy with or without rituximab and stem cell transplant and to see
    how well it works in treating patients with persistent or recurrent non-Hodgkin lymphoma
    that is resistant to chemotherapy. Biological therapies, such as lenalidomide, may stimulate
    the immune system in different ways and stop cancer cells from growing. Drugs used in
    chemotherapy, such as carmustine, etoposide, cytarabine, and melphalan, work in different
    ways to stop the growth of cancer cells, either by killing the cells or by stopping them
    from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in
    different ways. Some block the ability of cancer cells to grow and spread. Others find
    cancer cells and help kill them or carry cancer-killing substances to them.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To establish the maximum tolerated dose (MTD) of Lenalidomide given in the post
    transplant setting for a 12 month maintenance period.

    SECONDARY OBJECTIVES:

    I. To obtain preliminary estimates of the 1-year response rate, event-free and overall
    survival using this regimen.

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

    PRE-CONDITIONING (patients with CD20+ non-Hodgkin lymphoma): Patients receive rituximab
    intravenously (IV) per standard of care.

    PREPARATIVE REGIMEN: Patients receive carmustine IV on day -6, etoposide IV twice daily
    (BID) and cytarabine IV BID on days -5 through -2, and melphalan IV on day -1.

    AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION: Patients undergo stem cell infusion on
    day 0.

    MAINTENANCE THERAPY: Beginning approximately 100 days post-transplant, patients receive
    lenalidomide orally (PO) on days 1-21. Treatment repeats every 28 days for 12 courses in the
    absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up periodically.

    Trial Arms

    Name Type Description Interventions
    Treatment (stem cell transplantation) Experimental PRE-CONDITIONING (patients with CD20+ NHL): Patients receive rituximab IV per standard of care. PREPARATIVE REGIMEN: Patients receive carmustine IV on day -6, etoposide IV BID and cytarabine IV BID on days -5 through -2, and melphalan IV on day -1. AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION: Patients undergo stem cell infusion on day 0. MAINTENANCE THERAPY: Beginning approximately 100 days post-transplant, patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. lenalidomide, carmustine, etoposide, cytarabine, melphalan

    Eligibility Criteria

    Inclusion Criteria:

    - Persistent, or relapsed non-Hodgkin's lymphoma (NHL) (any histology) that is
    chemo-resistant (< a partial response [PR]), patients who have received >= 3 prior
    chemotherapy regimens, or patients with lymphomas that have a high relapse rate
    following autologous or syngeneic stem cell transplantation (transformed NHL,
    peripheral T-cell lymphoma [PTCL], mantle cell lymphoma [MCL], anaplastic lymphoma
    kinase [ALK]-negative anaplastic large cell lymphoma [ALCL, alk neg]), or patients
    with a positive positron emission tomography (PET) scan prior to transplant, and
    otherwise eligible for transplantation with adequate end-organ function

    - Patients that relapse within one year of diagnosis

    - Able to collect >= 1.5 x 10^6 CD34+/kg cell for transplantation

    - Absolute neutrophil count (ANC) >= 1000 cells/mm^3 and platelet count >= 60 mm^3 when
    maintenance Lenalidomide is started (day 100 [+/- 7 days] post-transplant)

    - 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, with the understanding that consent may be
    withdrawn by the subject at any time without prejudice to future medical care

    - Able to adhere to the study visit schedule and other protocol requirements

    - Expected survival duration of >= six months

    - Karnofsky Performance Status >= 70

    - Liver functions =< 2 x upper limits of normal (ULN) unless due to lymphoma or due to
    Gilberts disease

    - Serum creatinine < 2.0 mg/dL or calculated creatinine clearance > 50ml/min

    - Patients > age 60 or with clinical signs of heart disease must have ejection fraction
    >= 45% left ventricular ejection fraction (LVEF)

    - Patients with clinical signs of pulmonary insufficiency must have diffusion capacity
    of the lung for carbon monoxide (DLCO) to be measured at >= 50% of predicted value

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

    - Disease free of prior malignancies for >= 2 years with exception of currently treated
    basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
    or breast or low risk prostate cancer after curative therapy

    - All study participants must be registered into the mandatory RevAssist program, and
    be willing and able to comply with the requirements of RevAssist

    - Females of childbearing potential (FCBP) must have a negative serum or urine
    pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to
    and again within 24 hours of prescribing lenalidomide (prescriptions must be filled
    within 7 days)

    - 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 she starts
    taking lenalidomide

    - FCBP must also agree to ongoing pregnancy testing

    - Men must agree to use a latex condom during sexual contact with a FCBP even if they
    have had a successful vasectomy

    - Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
    intolerant to acetylsalicylic acid [ASA] may use warfarin or low molecular weight
    heparin)

    - Male subject agrees to use an acceptable method for contraception for the duration of
    the study

    Exclusion Criteria:

    - Chemosensitive NHL, except patients receiving >= 3 prior chemotherapy regimens, or
    patients having transformed NHL, PTCL, MCL or ALCL, alk neg

    - End-organ function not appropriate for transplantation

    - Inability to collect adequate stem cells

    - Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type
    A, B or C or active Hepatitis

    - Any serious medical condition, laboratory abnormality, or psychiatric illness that
    would prevent the subject from signing the informed consent form

    - Pregnant or breast feeding females (lactating females must agree not to breast feed
    while taking lenalidomide)

    - Known hypersensitivity to thalidomide

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

    - Any prior use of lenalidomide

    - Concurrent use of other anti-cancer agents or treatments

    - Serum creatinine >= 2.0mg/dL or calculated creatinine clearance =< 50ml/min

    - Total bilirubin >= 2 times upper limits of normal (unless due to Gilberts disease or
    NHL)

    - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 4 times the
    upper limits of normal

    - Active infection at the start of Lenalidomide

    - Myocardial infarction within 6 months prior to enrollment or has New York Heart
    Association (NYHA) Class III or IV heart failure uncontrolled angina, severe
    uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
    ischemia or active conduction system abnormalities

    - Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be
    documented by the investigator as not medically relevant

    - History of life threatening or recurrent thrombosis/embolism; patients may
    participate if they are adequately anticoagulated during the treatment

    - Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment

    Minimum Eligible Age: 19 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    MTD of lenalidomide, determined according to incidence of dose limiting toxicities (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

    Secondary Outcome Measures

    Event-free survival (Phase II)

    Overall survival (Phase II)

    Complete response (CR) rate (Phase II)

    Trial Keywords