Brief Title
Nivolumab and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma
Official Title
A Phase I/II Study of the PD-1 Antibody Nivolumab in Combination With Lenalidomide in Relapsed/Refractory Non-Hodgkin's Lymphoma (NHL) and Hodgkin's Disease (HD)
Brief Summary
This I/II trial studies the side effects and best dose of lenalidomide when given together
with nivolumab and to see how well they work in treating patients with non-Hodgkin or Hodgkin
lymphoma that has come back and does not respond to treatment. Monoclonal antibodies, such as
nivolumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in
chemotherapy, such as lenalidomide, work in different ways to stop the growth of tumor cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving nivolumab and lenalidomide may work better in treating patients with
non-Hodgkin or Hodgkin lymphoma.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of the combination of lenalidomide and nivolumab
in patients with relapsed/refractory non-Hodgkin lymphoma (NHL). (Phase I) II. To determine
the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the combination of
lenalidomide and nivolumab in patients with relapsed/refractory NHL. (Phase I) III. To
evaluate the feasibility and toxicities of the combination of lenalidomide and nivolumab in
patients with relapsed/refractory Hodgkin's disease (HD). (Phase IB) IV. To evaluate the
efficacy of the combination of lenalidomide and nivolumab in terms of overall response rate
in patients with relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell
lymphoma (DLBCL). (Phase II)
SECONDARY OBJECTIVES:
I. To evaluate the efficacy of the combination of lenalidomide and nivolumab in patients with
relapsed/refractory NHL in terms of overall response rate (ORR), duration of response (DOR),
progression-free survival (PFS) and overall survival (OS). (Phase I) II. To evaluate the
efficacy of the combination of lenalidomide and nivolumab in patients with
relapsed/refractory HD in terms of complete response rate (CR). (Phase IB) III. To evaluate
the efficacy of the combination of lenalidomide and nivolumab in patients with
relapsed/refractory HD in terms of duration of response (DOR), progression-free survival
(PFS) and overall survival (OS). (Phase IB) IV. To evaluate the efficacy of the combination
of lenalidomide and nivolumab in patients with relapsed/refractory FL and DLBCL in terms of
duration of response (DOR), progression-free survival (PFS) and overall survival (OS). (Phase
II)
TERTIARY OBJECTIVES:
I. To explore the relationship between prognostic parameters including ki-67 staining, PD-1
staining and cell of origin (activated B-cell or ABC versus germinal center B-cell or GCB)
with ORR to the combination of lenalidomide and nivolumab in patients with
relapsed/refractory NHL. (Phase I) II. To evaluate and monitor effects on B-, T-, and natural
killer (NK)-cell function with the combination of lenalidomide and nivolumab in patients with
relapsed/refractory NHL. (Phase I) III. To explore the relationship between prognostic
parameters including ki-67 staining, PD-1 staining and cell of origin (activated B-cell or
ABC versus germinal center B-cell or GCB) with ORR to the combination of lenalidomide and
nivolumab in patients with relapsed/refractory FL and DLBCL. (Phase II) IV. To evaluate and
monitor effects on B-, T-, and NK-cell function with the combination of lenalidomide and
nivolumab in patients with relapsed/refractory FL and DLBCL. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II
study.
Patients receive lenalidomide orally (PO) on days 1-21 and nivolumab intravenously (IV) over
60 minutes on days 1 and 15 of courses 1-4 and on day 1 of courses 5-12. Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years,
then every 6 months for up to 3 years.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Incidence of adverse events summarized by NCI CTCAE version 4
Secondary Outcome
Complete response rate (CR) in patients
Condition
Grade 3a Follicular Lymphoma
Intervention
Laboratory Biomarker Analysis
Study Arms / Comparison Groups
Treatment (lenalidomide, nivolumab)
Description: Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 60 minutes on days 1 and 15 of courses 1-4 and on day 1 of courses 5-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
36
Start Date
February 14, 2017
Completion Date
December 31, 2023
Primary Completion Date
December 31, 2023
Eligibility Criteria
Inclusion Criteria:
- PHASE I: Histologically confirmed B-cell NHL with any of the following subtypes:
DLBCL, mantle cell lymphoma (MCL), FL, marginal zone lymphoma (MZL) and
lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (LL/WM), Burkitt's lymphoma
(BL); patients with histological transformation to DLBCL from indolent lymphoma,
primary mediastinal lymphoma and grey zone lymphoma are eligible
- PHASE I: Histologically confirmed classical or lymphocyte predominant Hodgkin's
disease that is relapsed or refractory after at least one prior chemotherapy
- PHASE I: Patients must have received at least one prior therapy; prior autologous stem
cell transplant is permitted; patients with DLBCL who have not had prior high-dose
therapy (HDT)/autologous stem cell transplant (ASCT) must be ineligible for
transplant; prior lenalidomide is not permitted if patients have progressed on therapy
- PHASE IB DOSE EXPANSION: Histologically confirmed classical or lymphocyte predominant
Hodgkin's disease
- PHASE IB DOSE EXPANSION: Patients must have received at least one prior therapy; prior
autologous stem cell transplant is permitted; patients who have not had prior HDT/ASCT
must be ineligible for transplant; prior lenalidomide is not permitted if patients
have progressed on therapy
- PHASE II: Histologically confirmed B-cell NHL:
- Cohort 1: with only de novo DLBCL or transformed indolent Non-Hodgkin's lymphoma
(excludes Richter's syndrome).
- Cohort 2: with only FL of grade 1, 2 or 3a
- PHASE II: Patients must have received at least one prior therapy (in patients with
transformed DLBCL must have received at least one prior therapy; prior autologous stem
cell transplant is permitted; patients with DLBCL who have not had prior HDT/ASCT must
be ineligible for transplant; prior lenalidomide is not permitted if patients have
progressed on therapy
- Be willing and able to provide written informed consent/assent for the trial
- Have evaluable disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Absolute neutrophil count (ANC) >= 1,500 /mcL
- Platelets >= 100,000 /mcL in the absence of transfusion support within 7 days of
determining eligibility
- Hemoglobin >= 8 g/dL
- Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated
creatinine clearance (glomerular filtration rate [GFR] can also be used in place of
creatinine or creatinine clearance [CrCl]) >= 40 mL/min creatinine clearance
- Serum total bilirubin =< 1.5 X ULN OR except subjects with Gilbert syndrome, who can
have total bilirubin < 3.0 mg/dL
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 X
ULN
- Female subject of childbearing potential should have a negative urine or serum
pregnancy at screening and within 24 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
- 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; subjects should
agree to ongoing pregnancy testing during the course of the study and after the end of
study therapy; female subjects of childbearing potential are those who have not been
surgically sterilized or have not been free from menses for > 1 year
- Male subjects should agree to use an adequate method of contraception starting with
the first dose of study therapy through 120 days after the last dose of study therapy;
males must refrain from donating sperm during study participation and for 120 days
after the last dose of study medication
- Willing and able to receive adequate prophylaxis and/or therapy for thromboembolic
events
- Be willing and able to understand and give written informed consent and comply with
all study related procedures
Exclusion Criteria:
- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 3 weeks of the first dose of treatment
- 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; subjects may use topical or inhaled corticosteroids or low-dose steroids
(=< 20 mg of prednisone or equivalent per day) as therapy for comorbid conditions;
during study participation, subjects may receive systemic or enteric corticosteroids
as needed for treatment-emergent comorbid conditions
- Has a known history of active TB (bacillus tuberculosis)
- Hypersensitivity to nivolumab or lenalidomide or any of their excipients
- Has had a prior anti-cancer monoclonal antibody (mAb) within 2 weeks prior to study
day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events
due to agents administered more than 4 weeks earlier
- Has had prior chemotherapy or radiation therapy within 2 weeks prior to study day 1 or
who has not recovered (i.e., =< grade 1 or at baseline) from adverse events 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; patients must be 4 weeks out from major procedures
- Has a known additional malignancy that is progressing or requires active treatment;
exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer
- Has known active central nervous system (CNS) lymphoma
- Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs); replacement therapy (thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment; conditions expected to not recur in the absence of an
external trigger
- Has an active infection requiring intravenous systemic therapy
- Is unable to swallow capsules or malabsorption syndrome, disease or condition
significantly affecting gastrointestinal function
- Clinically significant cardiovascular disease with uncontrolled arrhythmia, New York
Association class 3 or 4 congestive heart failure, history of myocardial infarction
within 6 months, or prolonged corrected QT (QTc) > 500 msec
- 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
- Has progressed on prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Has progressed on prior therapy with lenalidomide
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
detected)
- Has a history of deep venous thrombosis/embolism, threatening thromboembolism or known
thrombophilia or are at a high risk for a thromboembolic event in the opinion of the
investigator and who are not willing/able to take venous thromboembolic event
prophylaxis during the entire treatment period
- Has a history of prior allogeneic hematopoietic cell transplant with a history of
prior Graft Versus Host Disease
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
David Bond, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03015896
Organization ID
OSU-16167
Secondary IDs
NCI-2016-01966
Responsible Party
Sponsor-Investigator
Study Sponsor
David Bond, MD
Collaborators
Bristol-Myers Squibb
Study Sponsor
David Bond, MD, Principal Investigator, Ohio State University Comprehensive Cancer Center
Verification Date
March 2023