Overview

Smart Start: A Phase II Study of Rituximab, Lenalidomide, and Ibrutinib

Status:
Active, not recruiting
Trial end date:
2023-03-31
Target enrollment:
0
Participant gender:
All
Summary
This phase II trial studies how well giving rituximab, lenalidomide, and ibrutinib with chemotherapy works in treating patients with high-risk diffuse large B-cell lymphoma. High-risk large B-cell lymphoma is a type of cancer of the immune system that is usually fast-growing in the body. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride, 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 rituximab, ibrutinib, and lenalidomide with combination chemotherapy may kill more cancer cells.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborators:
Celgene
Janssen Scientific Affairs, LLC
National Cancer Institute (NCI)
Treatments:
Antibodies
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Cortisone
Cyclophosphamide
Doxorubicin
Etoposide
Etoposide phosphate
Immunoglobulins
Lenalidomide
Liposomal doxorubicin
Podophyllotoxin
Prednisone
Rituximab
Thalidomide
Vincristine
Criteria
Inclusion Criteria:

- Histopathologically confirmed diagnosis of previously untreated DLBCL of the non-GCB
DLBCL subtype

- No prior treatment except a prior limited-field radiotherapy, a short course of
glucocorticoids =< 25 mg daily of prednisone equivalent which must cease prior to day
1 of cycle 1, and/or cyclophosphamide for an urgent lymphoma related problem at
diagnosis (e.g. epidural cord compression, superior vena cava syndrome)

- Patient or durable power of attorney (DPA) for healthcare must be able to understand
and voluntarily sign an Institutional Review Board (IRB) -approved informed consent
form

- Patients must have bi-dimensional measurable disease, as defined as radiographically
apparent disease with the longest dimension of >= 1.5 cm

- Patients with performance status of =< 3 (3 only allowed if decline in status is
deemed related to lymphoma and felt potentially reversible by the treating physician)

- Serum bilirubin < 1.5 x upper limit of normal (ULN) except in patients with Gilbert's
syndrome as defined by > 80% unconjugated bilirubin

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x
ULN or < 5 x ULN if hepatic metastases are present

- Absolute neutrophil count (ANC) > 1000/mm^3 unless deemed related to lymphoma
involvement in the bone marrow and felt potentially reversible by the treating
physician

- Platelets > 100,000/mm^3 unless deemed related to lymphoma involvement in the bone
marrow and felt potentially reversible by the treating physician

- Renal function assessed by calculated creatinine clearance:

- Calculated creatinine clearance >=30 ml/min by Cockcroft-Gault formula

- Patients must be willing to receive transfusions of blood products

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

- Women of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [beta-hCG]) or urine pregnancy test at screening and must adhere to the
scheduled pregnancy testing as required in the Revlimid REMS program

- Women of childbearing potential and men who are sexually active with a woman of
childbearing potential must be practicing a highly effective method of birth control
during and after the study (12 months for women and 3 months for men), consistent with
local regulations regarding the use of birth control methods for subjects
participating in this clinical study; men must agree to not donate sperm during and
for up to 3 months after their conclusion of therapy on study

- Able to take aspirin (81 mg) daily or alternative therapy as prophylactic
anticoagulation

Exclusion Criteria:

- Any serious medical condition including but not limited to uncontrolled hypertension,
uncontrolled congestive heart failure within past 6 months prior to screening (class 3
[moderate] or class 4 [severe] cardiac disease as defined by the New York Heart
Association Functional Classification), uncontrolled diabetes mellitus,
active/symptomatic coronary artery disease, chronic obstructive pulmonary disease
(COPD), left ventricular ejection fraction (LVEF) less than 40%, renal failure, active
infection, history of invasive fungal infection, moderate to severe hepatic disease
(Child Pugh class B or C), active hemorrhage, laboratory abnormality, or psychiatric
illness that, in the investigators opinion places the patient at unacceptable risk and
would prevent the subject from signing the informed consent form; patients with
history of cardiac arrhythmias should have cardiac evaluation and clearance

- Pregnant or lactating females

- Known hypersensitivity to lenalidomide or thalidomide, ibrutinib, rituximab,
etoposide, vincristine, doxorubicin, cyclophosphamide, or prednisone

- Known human immunodeficiency virus (HIV) infection; patients with active hepatitis B
infection (not including patients with prior hepatitis B vaccination; or positive
serum hepatitis B antibody); known hepatitis C infection is allowed as long as there
is no active disease and is cleared by gastrointestinal (GI) consultation

- All patients with central nervous system involvement with lymphoma

- Diagnosis of prior malignancy within the past 2 years with the exception of
successfully treated basal cell carcinoma, squamous cell carcinoma of the skin,
carcinoma "in situ" of the cervix or breast; history of other malignancies are allowed
if in remission (including prostate cancer patients in remission from radiation
therapy, surgery or brachytherapy), not actively being treated, with a life expectancy
> 3 years

- Significant neuropathy (grades 2 or grade 1 with pain) within 14 days prior to
enrollment

- Contraindication to any of the required concomitant drugs or supportive treatments or
intolerance to hydration due to preexisting pulmonary or cardiac impairment including
pleural effusion requiring thoracentesis or ascites requiring paracentesis not due to
lymphoma

- Patients with active pulmonary embolism or deep vein thrombosis (diagnosed within 30
days of study enrollment)

- Patients with severe bradycardia (heart rate < 40 beats per minute [bpm], hypotension,
light-headedness, syncope)

- Major surgery within 4 weeks of study entry, or wound that is not healed from prior
surgery or trauma

- History of stroke or intracranial hemorrhage within 6 months prior to study entry

- Requires anticoagulation with warfarin or equivalent vitamin K antagonists

- Requires chronic treatment with strong cytochrome P450, family 3, subfamily A (CYP3A)
inhibitors

- Vaccinated with live, attenuated vaccines within 4 weeks of study entry