Summary

for people ages 18 years and up (full criteria)
at La Jolla, California and other locations
study started
Divya T. Koura

Description

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.

Official Title

A Phase I Trial of the Combination of Lenalidomide and Blinatumomab in Patients With Relapsed or Refractory Non-Hodgkins Lymphoma (NHL)

Details

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

  1. 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.

Keywords

CD19 Positive Mediastinal Lymphoma 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 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 Antibodies Immunoglobulins Lenalidomide Thalidomide Antibodies, Monoclonal Antibodies, Bispecific Muromonab-CD3 Blinatumomab Laboratory Biomarker Analysis

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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
  • 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 m2 (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
  • 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/mm3 prior to beginning combination antiretroviral therapy (cART)

  • After HIV diagnosis and during treatment with cART, patients should have maintained CD4+ T-cells >= 350/mm3 prior to lymphoma diagnosis; patients who never immune reconstituted to a stable level above 350/mm3 are not eligible

  • At time of study entry CD4+ T-cells must have recovered from prior lymphoma therapy to >= 250/mm3

  • 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
  • Stavudine not allowed
  • Zidovudine not allowed
  • Patients must be willing to be followed at a minimum of approximately every 3 months by physician expert in HIV disease management

You CAN'T join if...

  • 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

Locations

  • UC San Diego Moores Cancer Center accepting new patients
    La Jolla California 92093 United States
  • City of Hope Comprehensive Cancer Center accepting new patients
    Duarte California 91010 United States
  • Los Angeles County-USC Medical Center currently not accepting new patients, but might later
    Los Angeles California 90033 United States
  • USC / Norris Comprehensive Cancer Center accepting new patients
    Los Angeles California 90033 United States
  • Keck Medical Center of USC Pasadena currently not accepting new patients, but might later
    Pasadena California 91105 United States

Details

Status
accepting new patients
Start Date
Sponsor
National Cancer Institute (NCI)
ID
NCT02568553
Phase
Phase 1
Lead Scientist
Divya T. Koura
Study Type
Interventional
Last Updated
August 2, 2018