Overview

Rituximab, Lenalidomide, and Nivolumab in Treating Participants With Relapsed or Refractory Non-Germinal Center Type Diffuse Large B Cell Lymphoma or Primary Central Nervous System Lymphoma

Status:
Terminated
Trial end date:
2019-04-16
Target enrollment:
0
Participant gender:
All
Summary
This phase I/II trial studies the side effects and best dose of lenalidomide when given in combination with rituximab and nivolumab and how well they work in treating participants with non-germinal center type diffuse large B cell lymphoma or primary central nervous system lymphoma that has come back or isn't responding to treatment. Monoclonal antibodies, such as rituximab and nivolumab, may interfere with ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rituximab, lenalidomide, and nivolumab may work better in treating participants with diffuse large B cell lymphoma.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Vanderbilt-Ingram Cancer Center
Collaborators:
Bristol-Myers Squibb
National Cancer Institute (NCI)
Treatments:
Antibodies, Monoclonal
Lenalidomide
Nivolumab
Rituximab
Thalidomide
Criteria
Inclusion Criteria:

- Understand and voluntarily sign an informed consent form.

- Able to adhere to the study visit schedule and other protocol requirements in the
opinion of the investigator

- Patients with histological confirmation of relapsed/refractory non-GCB type (using
Hans algorithm) diffuse large B cell lymphoma (DLBCL) or relapsed/refractory primary
CNS lymphoma (PCNSL) with at least one of the following characteristics:

- Definition of refractory disease: progression of disease based on Cheson criteria
for DLBCL or international primary CNS lymphoma cooperative group for PCNSL
either with nonresponse or progression within 3 months of prior therapy

- Definition of relapsed disease: progression of disease based on Cheson criteria
for DLBCL or International primary CNS lymphoma cooperative group for PCNSL at
least 3 months after prior therapy

- Definition of non-GCB subtype (Hans algorithm): cases will be subclassified based
on immunohistochemical staining with CD10, BCL-6 and MUM-1 as previously
described.

- Patients should have exhausted (or be ineligible for) approved therapies known to
provide clinical benefit for DLBCL or PCNSL (e.g. high dose chemotherapy with
autologous stem cell transplant, chimeric antigen receptor-transduced [CAR-T]
therapy, etc.).

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry.

- Absolute neutrophil count >= 1000/mm^3 within 45 days prior to initiation of therapy.
(Patients with documented marrow involvement (with lymphoma) or hypersplenism
secondary to involvement of the spleen by lymphoma at the time of randomization are
not required to meet the parameter).

- Platelet count >= 75K /mm^3 within 45 days prior to initiation of therapy. (Patients
with documented marrow involvement (with lymphoma) or hypersplenism secondary to
involvement of the spleen by lymphoma at the time of randomization are not required to
meet the parameter).

- Serum creatinine =< 2.0 mg/dL or creatinine clearance of > 40 ml/min within 45 days
prior to initiation of therapy. (Patients with documented marrow involvement (with
lymphoma) or hypersplenism secondary to involvement of the spleen by lymphoma at the
time of randomization are not required to meet the parameter).

- Total bilirubin =< 1.5 mg/dL within 45 days prior to initiation of therapy. (Patients
with documented marrow involvement (with lymphoma) or hypersplenism secondary to
involvement of the spleen by lymphoma at the time of randomization are not required to
meet the parameter).

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x
upper limit of normal (ULN) within 45 days prior to initiation of therapy. (Patients
with documented marrow involvement (with lymphoma) or hypersplenism secondary to
involvement of the spleen by lymphoma at the time of randomization are not required to
meet the parameter).

- Disease free of prior malignancies for >= 3 years with exception of currently treated
basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the
cervix or breast.

- All study participants must be registered into the mandatory Revlimid Risk Evaluation
and Mitigation Strategies (REMS) program, and be willing and able to comply with the
requirements of the Revlimid REMS program. program, and be willing and able to comply
with the requirements of the Revlimid REMS program.

* Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days and again
within 24 hours prior to prescribing lenalidomide for cycle 1 (prescriptions must be
filled within 7 days as required by the Revlimid REMS program) 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.

** A female of childbearing potential is a sexually mature female who: 1) has not
undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in
the preceding 24 consecutive months).

- Able to take aspirin (81 or 325 mg) daily or for thromboprophylaxis with lenalidomide.

Exclusion Criteria:

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent.

- Pregnant or breast feeding females (lactating females must agree not to breast feed
while taking lenalidomide).

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.

- Use of any other experimental drug or therapy within 28 days of baseline.

- Known hypersensitivity to thalidomide.

- Known prior development of erythema nodosum if characterized by a desquamating rash
while taking thalidomide or similar drugs.

- Concurrent use of other anti-cancer agents or treatments.

- Patients with a prior history of pulmonary toxicity due to medications (Ex: history of
carmustine [BCNU] toxicity).

- Active human immunodeficiency virus (HIV) infection or infectious hepatitis, type B or
C.

- Patients with a past or resolved hepatitis B virus (HBV) infection (defined as
the presence of hepatitis B core antibody [anti-HBc] and absence of hepatitis B
surface antigen [HBsAg]) may be included if HBV deoxyribonucleic acid (DNA) is
undetectable. If enrolled, patients must be willing to undergo monthly HBV DNA
testing.

- HIV positive patients may enroll if they meet all of the below criteria:

- HIV is sensitive to antiretroviral therapy.

- Must be willing to take effective antiretroviral therapy if indicated.

- No history of CD4 prior to or at the time of lymphoma diagnosis < 300
cells/mm^3.

- No history of acquired immunodeficiency syndrome (AIDS)-defining conditions.

- If on antiretroviral therapy, must not be taking zidovudine or stavudine.

- Must be willing to take prophylaxis for pneumocystis jiroveci pneumonia
(PCP) during therapy and until at least 2 months following the completion of
therapy or until the CD4 cells recover to over 250 cells/mm^3, whichever
occurs later.

- A diagnosis of deep vein thromboses in the preceding four weeks of study enrollment.

- Subjects with active interstitial pneumonitis.

- Patient with active, uncontrolled infections (patients must be afebrile for > 48 hours
off antibiotics).

- Patient with clinically significant history of liver disease, including viral or other
hepatitis, current alcohol abuse, or cirrhosis.

- Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
requiring hormone replacement, psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted
to enroll.

- Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results or that could increase risk
to the patient, including renal disease that would preclude chemotherapy
administration or pulmonary disease (including obstructive pulmonary disease and
history of bronchospasm).

- Major surgery within 4 weeks prior to cycle 1, other than for diagnosis.

- Malabsorption syndrome or other condition that precludes oral route of administration
of lenalidomide.

- Vaccinations with a live vaccine within 28 days prior to start of treatment or need
for live vaccine at any time during study treatment.

- Patient must not have serious medical or psychiatric illness likely to interfere with
participation in this clinical study in the opinion of the investigator.

- Inability to swallow oral medications.

- Subjects with New York Heart Association (NYHA) class III or IV heart failure.