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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University of Nebraska
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01035463
First received: December 17, 2009
Last updated: November 11, 2013
Last verified: November 2013
  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.


Condition Intervention Phase
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
Waldenström Macroglobulinemia
Drug: lenalidomide
Biological: rituximab
Procedure: autologous hematopoietic stem cell transplantation
Drug: carmustine
Drug: etoposide
Drug: cytarabine
Drug: melphalan
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Lenalidomide Maintenance Following BEAM (+/- Rituximab) for Chemo-Resistant or High Risk Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

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) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Event-free survival (Phase II) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to estimate the event-free survival distribution.

  • Overall survival (Phase II) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to estimate the overall survival distribution.

  • Complete response (CR) rate (Phase II) [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
    Estimated as the proportions of patients who achieve a CR or PR divided by the number of evaluable patients. Each will be reported with their associated 95% confidence interval.


Estimated Enrollment: 50
Study Start Date: November 2009
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (stem cell transplantation)

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.

Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous hematopoietic stem cell transplant
Drug: carmustine
Given IV
Other Names:
  • BCNU
  • BiCNU
  • bis-chloronitrosourea
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin

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

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Persistent, or relapsed non-Hodgkin's lymphoma (NHL) (any histology) that is chemo-resistant ( = 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01035463

Locations
United States, Kansas
University of Kansas Hospital - Westwood Cancer Center Recruiting
Westwood, Kansas, United States, 66205
Contact: Siddhartha Ganguly    913-588-6029    sganguly@kumc.edu   
Principal Investigator: Siddhartha Ganguly         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Julie M. Vose    402-559-3848    jmvose@unmc.edu   
Principal Investigator: Julie M. Vose         
United States, Ohio
Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Basem M. William    216-286-4133    bmw93@case.edu   
Principal Investigator: Basem M. William         
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Julie Vose University of Nebraska
  More Information

No publications provided by University of Nebraska

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Julie M Vose, MD, Principal Investigator, University of Nebraska
ClinicalTrials.gov Identifier: NCT01035463     History of Changes
Other Study ID Numbers: 446-08, NCI-2009-01436, RV-LYM-PI-328, 446-08, P30CA036727
Study First Received: December 17, 2009
Last Updated: November 11, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Mycoses
Mycosis Fungoides
Burkitt Lymphoma
Immunoblastic Lymphadenopathy
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Sezary Syndrome
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Mantle-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Experimental

ClinicalTrials.gov processed this record on July 29, 2014