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

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ClinicalTrials.gov Identifier: NCT02568553
Recruitment Status : Suspended (Other - Pending amendment with MTD dose for expansion)
First Posted : October 6, 2015
Last Update Posted : July 30, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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 or disease Intervention/treatment Phase
CD19 Positive Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma Recurrent 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 Mediastinal Lymphoma Recurrent Non-Hodgkin Lymphoma Recurrent Small Lymphocytic Lymphoma Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma Refractory Burkitt Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Follicular Lymphoma Refractory Mantle Cell Lymphoma Refractory Marginal Zone Lymphoma Refractory Mediastinal Lymphoma Refractory Non-Hodgkin Lymphoma Refractory Small Lymphocytic Lymphoma Biological: Blinatumomab Other: Laboratory Biomarker Analysis Drug: Lenalidomide Phase 1

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 of lenalidomide.

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 cycles 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. Cycles 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
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)
Actual Study Start Date : June 14, 2016
Estimated Primary Completion Date : December 31, 2019


Arm Intervention/treatment
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 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 cycles 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. Cycles 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




Primary Outcome Measures :
  1. Incidence of toxicity [ Time Frame: Up to 24 months ]
    Will be graded as according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 beginning April 1, 2018). Toxicities (grade, type, cycle, and attribution) experienced will be listed for each patient and summarized using standard descriptive methods.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Changes in the production of interferon (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 available for these comparisons.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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); patients previously treated with CD19-targeted therapy (including chimeric antigen receptor T-cells [CAR T]) must have a subsequent biopsy and/or flow cytometry confirming CD19 positivity
  • 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
  • AST (SGOT)/ALT(SGPT) (only if elevated liver function tests [LFTs] are due to disease) =< 5.0 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 (e.g. rituximab alone) regimens and not currently eligible for standard curative options; steroids alone and local radiation do not count as regimens; radiation to > 1 site and transplant are considered prior 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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • 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 because lenalidomide is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02568553


Locations
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United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
Los Angeles County-USC Medical Center
Los Angeles, California, United States, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Keck Medical Center of USC Pasadena
Pasadena, California, United States, 91105
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Connecticut
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, United States, 06510
Yale University
New Haven, Connecticut, United States, 06520
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Northside Hospital
Atlanta, Georgia, United States, 30342
United States, Kansas
University of Kansas Clinical Research Center
Fairway, Kansas, United States, 66205
University of Kansas Cancer Center
Kansas City, Kansas, United States, 66160
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States, 66205
United States, Kentucky
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States, 40536
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
United States, Tennessee
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States, 75390
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Joseph M Tuscano City of Hope Comprehensive Cancer Center LAO

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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 )
First Posted: October 6, 2015    Key Record Dates
Last Update Posted: July 30, 2019
Last Verified: July 2019

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Hodgkin Disease
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
Antibodies, Monoclonal
Antibodies, Bispecific
Muromonab-CD3