This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Lenalidomide and Blinatumomab in Treating Patients With Relapsed Non-Hodgkin Lymphoma

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02568553
First received: October 5, 2015
Last updated: July 10, 2017
Last verified: May 2017
  Purpose
This phase I trial studies the side effects and best dose of lenalidomide and blinatumomab when given together in treating patients with non-Hodgkin lymphoma that has returned after a period of improvement. Biological therapies, such as lenalidomide and blinatumomab, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing.

Condition Intervention Phase
B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma CD19 Positive Mediastinal Lymphoma Recurrent Adult Burkitt Lymphoma Recurrent Diffuse Large B-Cell 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 Non-Hodgkin Lymphoma Recurrent Small Lymphocytic Lymphoma Biological: Blinatumomab Other: Laboratory Biomarker Analysis Drug: Lenalidomide Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase I Trial of the Combination of Lenalidomide and Blinatumomab in Patients With Relapsed or Refractory Non-Hodgkins Lymphoma (NHL)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence of toxicity as coded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 24 months ]
    Toxicities (grade, type, cycle, and attribution) experienced will be listed for each patient and summarized using standard descriptive methods.


Secondary Outcome Measures:
  • Changes in the frequency of CD4+ T cells [ Time Frame: Baseline to up to day 57 ]
    Will be assessed and compared at each time point, using regression methods that incorporate repeated measures. For each of the first 2 CD4+ measures, will compare the day 0 values (prior to any treatment) to the day 15 values (after 2 weeks of blinatumomab) and the day 57 (after 4 weeks of the both blinatumomab and lenalidomide) to the day 15 value. Additional analysis, will be undertaken to explore the relationship between changes (or lack of changes) and response. The paired-sample t-test will be used to provide a sense of the power/sensitivity that will be available for these comparisons.

  • Changes in the production of INF-gamma from CD4+ T cells [ Time Frame: Baseline to up to day 57 ]
    Will be assessed and compared at each time point, using regression methods that incorporate repeated measures. For each of the first CD8+ T-cell frequencies and INF-gamma production, will compare the day 0 values (prior to any treatment) to the day 15 values (after 2 weeks of blinatumomab) and the day 57 (after 4 weeks of the both blinatumomab and lenalidomide) to the day 15 value. Additional analysis, will be undertaken to explore the relationship between changes (or lack of changes) and response. The paired-sample t-test will be used to provide a sense of the power/sensitivity that will be a

  • Clinical anti-tumor response (complete response and partial response as per International workshop lymphoma response criteria) [ Time Frame: Up to 24 months ]
    Will be summarized using standard descriptive methods.


Estimated Enrollment: 36
Actual Study Start Date: June 14, 2016
Estimated Primary Completion Date: December 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (blinatumomab, lenalidomide)

INDUCTION: Patients receive blinatumomab IV continuously on days 1-56 and lenalidomide PO on days 29-49 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients achieving response receive including stable disease blinatumomab IV continuously on days 1-7 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receiving response including stable disease after completion of Consolidation receive lenalidomide PO on days 1-21. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Blinatumomab
Given IV
Other Names:
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • Blincyto
  • MEDI-538
  • MT-103
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of lenalidomide when given in combination with blinatumomab in the proposed regimen.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity anti-tumor response (complete response [CR] and partial response [PR] as per International workshop lymphoma response criteria).

II. To investigate the immune response to blinatumomab alone and in combination with lenalidomide.

III. To document the infection rate with a 96-hour bag change schedule for blinatumomab.

OUTLINE: This is a dose-escalation study.

INDUCTION: Patients receive blinatumomab intravenously (IV) continuously on days 1-56 and lenalidomide orally (PO) on days 29-49 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients achieving response including stable disease receive blinatumomab IV continuously on days 1-7 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receiving response including stable disease after completion of Consolidation receive lenalidomide PO on days 1-21. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed relapsed cluster of differentiation (CD)19+ non-Hodgkin lymphoma (NHL) (included in this category are follicular grade I, II, III, marginal zone, mantle cell, gray zone, primary mediastinal, Burkitt's, diffuse large B cell, small lymphocytic lymphoma)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
  • Absolute neutrophil count > 1000/mcL
  • Platelets >= 50,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Body surface area (BSA)-normalized creatinine clearance >= 60 mL/min/1.73 m^2 (using Cockcroft-Gault creatinine clearance [CrCl])
  • Patients must have had at least two prior chemotherapeutic or biologic (ie. rituximab alone) regimens and not currently eligible for standard curative options; steroids alone and local radiation do not count as regimens
  • Any prior therapy must have been completed at least 4 weeks prior to entry into the study
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and 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; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Patients must have radiographically measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan; lesions in previously irradiated anatomic areas (external beam radiation) cannot be considered target lesions unless there has been documented growth of those lesions after radiotherapy
  • Ability to understand and the willingness to sign a written informed consent document
  • Human immunodeficiency virus (HIV) infected patients are eligible provided they meet all the other eligibility criteria of the study in addition to the following:

    • No history of acquired immune deficiency syndrome (AIDS)-defining conditions other than lymphoma or history of CD4+ T-cells below 200/mm^3 prior to beginning combination antiretroviral therapy (cART)
    • After HIV diagnosis and during treatment with cART, patients should have maintained CD4+ T-cells >= 350/mm^3 prior to lymphoma diagnosis; patients who never immune reconstituted to a stable level above 350/mm^3 are not eligible
    • At time of study entry CD4+ T-cells must have recovered from prior lymphoma therapy to >= 250/mm^3
    • At the time of study entry the HIV viral load must be undetectable by standard laboratory assay
    • During prior lymphoma therapy, patients must not have experienced documented infections attributed to the HIV+ status
    • No history of non-adherence to cART and willing to adhere to cART while on study
    • Antiretroviral drugs with overlapping or similar toxicity profiles as study agents not allowed:

      • Efavirenz not allowed due to potential central nervous system (CNS) toxicity
      • Stavudine not allowed due to potential neuropathic effects
      • Zidovudine not allowed due to myelosuppressive effects
    • Patients must be willing to be followed at a minimum of approximately every 3 months by physician expert in HIV disease management

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide and blinatumomab or other agents used in study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with lenalidomide
  • Concurrent use of other anti-cancer agents or treatments
  • Known active hepatitis, type B or C; patients on suppressive therapy with a negative viral load and no evidence of hepatic damage are eligible
  • Prior treatment with blinatumomab or CD-directed CAR T-cell therapy
  • Prior treatment with lenalidomide within 8 weeks prior to entering the study
  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: NCT02568553

Locations
United States, California
City of Hope Comprehensive Cancer Center LAO Recruiting
Duarte, California, United States, 91010
Contact: Joseph M. Tuscano    916-734-3771    jtuscano@ucdavis.edu   
Principal Investigator: Joseph M. Tuscano         
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Jasmine M. Zain    800-826-4673    becomingapatient@coh.org   
Principal Investigator: Jasmine M. Zain         
Los Angeles County-USC Medical Center Suspended
Los Angeles, California, United States, 90033
USC / Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Mojtaba Akhtari    323-865-0451      
Principal Investigator: Mojtaba Akhtari         
Keck Medical Center of USC Pasadena Suspended
Pasadena, California, United States, 91105
University of California Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Joseph M. Tuscano    916-734-3089      
Principal Investigator: Joseph M. Tuscano         
United States, Connecticut
Smilow Cancer Center/Yale-New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: Gottfried von Keudell    203-785-5702      
Principal Investigator: Gottfried von Keudell         
Yale University Recruiting
New Haven, Connecticut, United States, 06520
Contact: Gottfried von Keudell    203-785-5702      
Principal Investigator: Gottfried von Keudell         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Julio C. Chavez    800-456-7121    canceranswers@moffitt.org   
Principal Investigator: Julio C. Chavez         
United States, Kentucky
University of Kentucky/Markey Cancer Center Suspended
Lexington, Kentucky, United States, 40536
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Nina D. Wagner-Johnston    410-955-8804    jhcccro@jhmi.edu   
Principal Investigator: Nina D. Wagner-Johnston         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Basem M. William    800-293-5066    Jamesline@osumc.edu   
Principal Investigator: Basem M. William         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Joseph Tuscano City of Hope Comprehensive Cancer Center LAO
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02568553     History of Changes
Other Study ID Numbers: NCI-2015-01640
NCI-2015-01640 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PHI-79
9924 ( Other Identifier: City of Hope Comprehensive Cancer Center LAO )
9924 ( Other Identifier: CTEP )
UM1CA186644 ( U.S. NIH Grant/Contract )
UM1CA186717 ( U.S. NIH Grant/Contract )
Study First Received: October 5, 2015
Last Updated: July 10, 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Hodgkin Disease
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Leukemia, Lymphocytic, Chronic, B-Cell
Burkitt Lymphoma
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Antibodies
Immunoglobulins
Lenalidomide
Thalidomide
Antibodies, Monoclonal
Antibodies, Bispecific

ClinicalTrials.gov processed this record on July 27, 2017