The goal of this clinical research study is to learn if the combination of pembrolizumab and
rituximab can help to control relapsed FL. The safety of this combination will also be
studied.
Study Drug Administration:
If you are found to be eligible for this study, you will receive rituximab and pembrolizumab
in 21-day study cycles.
On Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycle 2, you will receive rituximab by vein.
The first infusion takes 6-8 hours. After that, infusions take about 4 hours each.
On Day 2 of Cycles 1 and 2 and on Day 1 of Cycles 3-16, you will receive pembrolizumab by
vein over 1 hour.
Study Visits:
On Day 1 of Cycle 1, your vital signs will be recorded.
On Day 22 of Cycle 2, you will have a physical exam.
On Day 1 of Cycles 3-16:
- You will have a physical exam.
- Blood (about 2 tablespoons) will be drawn for routine tests. Every 2 cycles, part of
this sample will also be used to check your thyroid function. Every 4 cycles, part of
this sample will also be used to check the status of your immune system.
On Day 1 of Cycles 5, 9, and 13:
- Urine will be collected for routine tests.
- You will have a CT scan to check the status of the disease (Cycle 5 only).
On Day 1 of Cycle 8, you will have a PET/CT scan to check the status of the disease.
At any time, if your doctor think it is needed, you may have a bone marrow biopsy and
aspirate and/or a CT or PET/CT scan to check the status of the disease.
Length of Study:
You may take rituximab for 2 cycles and pembrolizumab for up to 16 cycles. You will no
longer be able to receive the drugs if the disease gets worse, if intolerable side effects
occur, or if you are unable to follow study directions.
Your participation on the study will be over once you have completed follow-up.
End-of-Treatment Visit:
After you stop receiving the study drug(s):
- You will have a physical exam.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- If your doctor thinks it is needed, you will have a PET/CT scan to check the status of
the disease.
Long Term Follow-Up:
30 days after your End-of-Treatment visit:
- You will have a physical exam.
- Blood (about 2 tablespoons) will be drawn for routine tests, to check your thyroid
function, and to check the status of your immune system.
- Urine will be collected for routine tests.
Every 3 months for 1 year and every 6 months after that until you start a new therapy, the
disease gets worse, or the study ends:
- You will have a physical exam.
- Blood (about 2 tablespoons) will be drawn for routine tests, to check your thyroid
function, and to check the status of your immune system.
- You will have a CT scan to check the status of the disease.
This is an investigational study. Pembrolizumab is FDA approved and commercially available
for the treatment of melanoma. Rituximab is FDA approved and commercially available for the
treatment of non-Hodgkin's lymphoma and certain types of leukemia. The combination of these
drugs to treat FL is investigational. The study doctor can describe how the study drugs are
designed to work.
Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.
Inclusion Criteria:
1. Male or female subjects with histologic proof of follicular lymphoma grade 1, grade
2, or grade 3a relapsing after at least one prior systemic therapy that included
rituximab. Patients should have rituximab-sensitive disease defined as a documented
complete or partial response lasting at least 6 months after the last rituximab-based
therapy.
2. Either the subject or his/her legally authorized representative be willing and able
to provide written informed consent for the trial.
3. Be >/= 18 years of age on day of signing informed consent.
4. Have measurable disease (>/= 1.5 cm in the longest diameter for nodal or extranodal
disease).
5. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale.
6. Demonstrate adequate organ function as defined below, all screening labs should be
performed within 28 days of treatment initiation. Hematological: Absolute neutrophil
count (ANC) >/=1.0 × 10^9/L; Platelets >/=75 × 10^9/L; Hemoglobin >/= 8.0 g/dL; Serum
creatinine OR Measured or calculated creatinine clearance (GFR can also be used in
place of creatinine or CrCl) (Creatinine clearance will be calculated per
institutional standard.) </=1.5 × upper limit of normal (ULN) OR >/=60 mL/min GFR or
CrCl for subjects with creatinine levels > 1.5 × institutional ULN; Hepatic: Serum
total bilirubin </= 1.5 × ULN OR Direct bilirubin </= ULN for subjects with total
bilirubin levels > 1.5 ULN;
7. #6 cont...aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase
(SGOT) and alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase (SGPT)
</= 2.5 × ULN OR </= 5 × ULN for subjects with lymphoma in the liver; Coagulation:
International Normalized Ratio (INR) or Prothrombin Time (PT) </=1.5 × ULN unless
subject is receiving anticoagulant therapy as long as PT or Partial Thromboplastin
Time (PTT) is within therapeutic range of intended use of anticoagulants; Activated
Partial Thromboplastin Time (aPTT) </=1.5 × ULN unless subject is receiving
anticoagulant therapy as long as PT or PTT is within therapeutic range of intended
use of anticoagulants
8. Female subject of childbearing potential should have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required.
9. Female subjects of childbearing potential should be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the
course of the study through 120 days after the last dose of study medication. Female
subjects of childbearing potential are those who have not been surgically sterilized
or have not been free from menses for > 1 year.
10. Male subjects should agree to use two methods of contraception starting with the
first dose of study therapy through 120 days after the last dose of study therapy.
Exclusion Criteria:
1. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study drug or using an investigation device
within 4 weeks of the first dose of treatment.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of
trial treatment.
3. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has
not recovered (i.e., </= Grade 1 or at baseline) from AEs due to agents administered
more than 4 weeks earlier.
4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., </= Grade 1 or at
baseline) from AEs due to a previously administered agent. - Note: Subjects with </=
Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting therapy.
5. Has a known additional malignancy that is progressing and requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, or in situ cervical cancer that has undergone potentially curative therapy.
6. Has known active central nervous system (CNS) lymphoma and/or lymphomatous
meningitis. Subjects with previously treated CNS lymphoma and/or lymphomatous
meningitis may participate provided they are stable (without evidence of progression
by imaging for at least four weeks prior to the first dose of trial treatment and any
neurologic symptoms have returned to baseline), have no evidence of new or enlarging
brain metastases, and are not using steroids for at least 7 days prior to trial
treatment.
7. No active autoimmune disease that has required systemic treatment in past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment. Subjects with vitiligo or resolved childhood asthma/atopy
would be an exception to this rule. Subjects that require intermittent use of
bronchodilators, local steroid injections or inhaled or topical steroids would not be
excluded from the study. Subjects with hypothyroidism stable on hormone replacement
or Sjorgen's syndrome will not be excluded from the study.
8. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
9. Has an active infection requiring systemic therapy.
10. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the best
interest of the subject to participate, in the opinion of the treating investigator.
11. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
12. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.
13. .Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
or checkpoint pathways).- Note: Subjects that received prior therapy with pidilizumab
are an exception to this criterion and may qualify for the study.
14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
16. Has received a live vaccine within 30 days prior to the first dose of trial
treatment.
