Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: Lenalidomide Maintenance Therapy After High Dose BEAM With or Without Rituximab

Summary: 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.

Eligibility: 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

Relevance to patient case: not relevant