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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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified December 2014 by Julie M Vose, MD, University of Nebraska.
Recruitment status was:  Recruiting
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01035463
First received: December 17, 2009
Last updated: December 2, 2014
Last verified: December 2014
  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: 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 Julie M Vose, MD, 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 ]

Secondary Outcome Measures:
  • Event-free survival (Phase II) [ Time Frame: 1 year ]
    The Kaplan-Meier method will be used to estimate the event-free survival distribution.

  • Overall survival (Phase II) [ Time Frame: 1 year ]
    The Kaplan-Meier method will be used to estimate the overall survival distribution.

  • Complete response (CR) rate (Phase II) [ Time Frame: At 1 year ]
    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   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  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
National Cancer Institute (NCI)
Investigators
Principal Investigator: Julie Vose University of Nebraska
  More Information

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 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RV-LYM-PI-328
446-08 ( Other Identifier: University of Nebraska Medical Center )
P30CA036727 ( U.S. NIH Grant/Contract )
Study First Received: December 17, 2009
Last Updated: December 2, 2014

Additional relevant MeSH terms:
Lymphoma
Syndrome
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Leukemia, Lymphocytic, Chronic, B-Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, Large B-Cell, Diffuse
Burkitt Lymphoma
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Plasmablastic Lymphoma
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Waldenstrom Macroglobulinemia
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Lymphomatoid Granulomatosis
Lymphoma, Extranodal NK-T-Cell
Immunoblastic Lymphadenopathy
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 16, 2017