Smart Start: A Phase II Study of Rituximab, Lenalidomide, and Ibrutinib
NCT ID: NCT02636322
Last Updated: 2024-03-13
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
60 participants
INTERVENTIONAL
2016-03-29
2022-10-24
Brief Summary
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Detailed Description
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I. To determine the overall response rate at the end of 2 cycles of therapy with rituximab, lenalidomide, and ibrutinib in patients with high risk newly diagnosed non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL).
II. To determine the complete response rate at the end of 6 cycles of therapy with rituximab, lenalidomide, and ibrutinib combined with chemotherapy (cyclophosphamide, doxorubicin hydrochloride \[hydroxydaunorubicin hydrochloride\], vincristine sulfate \[Oncovin\], prednisone \[CHOP\] or etoposide, prednisone, vincristine sulfate \[Oncovin\], cyclophosphamide, doxorubicin hydrochloride \[hydroxydaunorubicin hydrochloride\] \[EPOCH\]) in patients with high risk newly diagnosed non-GCB DLBCL.
SECONDARY OBJECTIVES:
I. To determine the overall response rate, landmark survival outcomes (progression free and overall survival), and safety of lenalidomide and ibrutinib with chemotherapy (CHOP or EPOCH) in patients with high risk newly diagnosed non-GCB DLBCL.
II. To evaluate descriptively the complete response rate in rituximab, lenalidomide, ibrutinib (RLI)-CHOP and in RLI-EPOCH.
EXPLORATORY OBJECTIVES:
I. To evaluate the baseline and therapy induced changes in the profile of mutations, gene expression, minimal residual disease clonotype levels, immune cell subsets, and tumor protein expression in tumor biopsy and blood samples in patients with high risk newly diagnosed non-GCB DLBCL.
OUTLINE:
SMART START: Patients receive rituximab intravenously (IV) over 4-6 hours on day 1, lenalidomide orally (PO) once daily (QD) on days 1-10, and ibrutinib PO QD on days 1-21. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity.
RLI WITH EPOCH: After SMART START therapy, patients receive rituximab IV over 4-6 hours on day 1, lenalidomide PO QD on days 1-10, and ibrutinib PO QD on days 1-21. Patients also receive etoposide IV over 24 hours on days 1-4, prednisone PO QD on days 1-5, vincristine sulfate IV over 24 hours on days 1-4, doxorubicin hydrochloride IV over 24 hours on days 1-4, and cyclophosphamide IV over 1 hour on day 5. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
RLI WITH R-CHOP: After SMART START therapy, patients receive rituximab IV over 4-6 hours on day 1, lenalidomide PO QD on days 1-10, and ibrutinib PO QD on days 1-21. Patients also receive prednisone PO QD on days 1-5, vincristine sulfate IV over 1 hour on day 1, doxorubicin hydrochloride IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 4 months for another year.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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RLI WITH EPOCH
SMART START: Patients receive rituximab IV over 4-6 hours on day 1, lenalidomide PO QD on days 1-10, and ibrutinib PO QD on days 1-21. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity.
After SMART START therapy, patients receive rituximab IV over 4-6 hours on day 1, lenalidomide PO QD on days 1-10, and ibrutinib PO QD on days 1-21. Patients also receive etoposide IV over 24 hours on days 1-4, prednisone PO QD on days 1-5, vincristine sulfate IV over 24 hours on days 1-4, doxorubicin hydrochloride IV over 24 hours on days 1-4, and cyclophosphamide IV over 1 hour on day 5. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Cyclophosphamide
Given IV
Doxorubicin Hydrochloride
Given IV
Etoposide
Given IV
Ibrutinib
Given PO
Lenalidomide
Given PO
Prednisone
Given PO
Rituximab
Given IV
Vincristine Sulfate
Given IV
RLI WITH R-CHOP
SMART START: Patients receive rituximab IV over 4-6 hours on day 1, lenalidomide PO QD on days 1-10, and ibrutinib PO QD on days 1-21. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity.
After SMART START therapy, patients receive rituximab IV over 4-6 hours on day 1, lenalidomide PO QD on days 1-10, and ibrutinib PO QD on days 1-21. Patients also receive prednisone PO QD on days 1-5, vincristine sulfate IV over 1 hour on day 1, doxorubicin hydrochloride IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Cyclophosphamide
Given IV
Doxorubicin Hydrochloride
Given IV
Ibrutinib
Given PO
Lenalidomide
Given PO
Prednisone
Given PO
Rituximab
Given IV
Vincristine Sulfate
Given IV
Interventions
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Cyclophosphamide
Given IV
Doxorubicin Hydrochloride
Given IV
Etoposide
Given IV
Ibrutinib
Given PO
Lenalidomide
Given PO
Prednisone
Given PO
Rituximab
Given IV
Vincristine Sulfate
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
M.D. Anderson Cancer Center
OTHER
Responsible Party
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Principal Investigators
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Jason Westin
Role: PRINCIPAL_INVESTIGATOR
M.D. Anderson Cancer Center
Locations
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M D Anderson Cancer Center
Houston, Texas, United States
Countries
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References
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Westin J, Davis RE, Feng L, Hagemeister F, Steiner R, Lee HJ, Fayad L, Nastoupil L, Ahmed S, Rodriguez A, Fanale M, Samaniego F, Iyer SP, Nair R, Oki Y, Fowler N, Wang M, Ma MCJ, Vega F, McDonnell T, Pinnix C, Griffith D, Lu Y, Tewari S, Sun R, Scott DW, Flowers CR, Neelapu S, Green MR. Smart Start: Rituximab, Lenalidomide, and Ibrutinib in Patients With Newly Diagnosed Large B-Cell Lymphoma. J Clin Oncol. 2023 Feb 1;41(4):745-755. doi: 10.1200/JCO.22.00597. Epub 2022 Aug 11.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Related Links
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MD Anderson Cancer Center
Other Identifiers
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NCI-2016-00017
Identifier Type: REGISTRY
Identifier Source: secondary_id
2015-0147
Identifier Type: OTHER
Identifier Source: secondary_id
2015-0147
Identifier Type: -
Identifier Source: org_study_id
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