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

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.

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