Clinical trial NCT02568553: Lenalidomide and Blinatumomab for the Treatment of Relapsed Non-Hodgkin Lymphoma
Official title: A Phase I Trial of the Combination of Lenalidomide and Blinatumomab in Patients With Relapsed or Refractory Non-Hodgkins Lymphoma (NHL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: 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 Grade 3a Follicular Lymphoma
Recurrent Grade 3b Follicular Lymphoma
Recurrent Gray-Zone Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mediastinal Lymphoma
Recurrent Non-Hodgkin Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Burkitt Lymphoma
Refractory Diffuse Large B-Cell Lymphoma
Refractory Follicular Lymphoma
Refractory Grade 1 Follicular Lymphoma
Refractory Grade 2 Follicular Lymphoma
Refractory Grade 3 Follicular Lymphoma
Refractory Grade 3a Follicular Lymphoma
Refractory Gray-Zone Lymphoma
Refractory Mantle Cell Lymphoma
Refractory Marginal Zone Lymphoma
Refractory Mediastinal Lymphoma
Refractory Non-Hodgkin Lymphoma
Refractory Small Lymphocytic Lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2015-10-06
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 (relapsed). Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread.

Detailed description: PRIMARY OBJECTIVE:

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.

Eligibility 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
* 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; radiographically measurable disease is 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:

  * 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
* 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 lenalidomide within 8 weeks prior to entering the study

Primary outcomes:
measure: Incidence of toxicity
timeFrame: Up to 24 months
Secondary outcomes:
measure: Clinical anti-tumor response (complete response and partial response as per International workshop lymphoma response criteria)
timeFrame: Up to 24 months
measure: Changes in the frequency of CD4+ T cells
timeFrame: Baseline to up to day 57
measure: Changes in the production of interferon (INF)-gamma from CD4+ T cells
timeFrame: Baseline to up to day 57
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles General Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Pasadena
country: United States
facility: Keck Medical Center of USC Pasadena
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Smilow Cancer Center/Yale-New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Fairway
country: United States
facility: University of Kansas Clinical Research Center
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Hospital-Westwood Cancer Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center - University Hospital
state: Wisconsin
Study officials:
affiliation: City of Hope Comprehensive Cancer Center LAO
name: Joseph M Tuscano
role: PRINCIPAL_INVESTIGATOR
References: