Combination Chemotherapy, Rituximab, and Ixazomib Citrate in Treating Patients With Non-Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT02481310|
Recruitment Status : Recruiting
First Posted : June 25, 2015
Last Update Posted : May 2, 2018
|Condition or disease||Intervention/treatment||Phase|
|Adult Burkitt Lymphoma B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma Diffuse Large B-Cell Lymphoma MYC Gene Mutation Plasmablastic Lymphoma||Drug: Cyclophosphamide Drug: Cytarabine Drug: Doxorubicin Hydrochloride Drug: Etoposide Drug: Ixazomib Citrate Other: Laboratory Biomarker Analysis Drug: Methotrexate Drug: Prednisone Biological: Rituximab Drug: Therapeutic Hydrocortisone Drug: Vincristine Sulfate||Phase 1 Phase 2|
I. To evaluate the safety of ixazomib (ixazomib citrate) given with dose-adjusted etoposide, prednisone, vincristine (vincristine sulfate), cyclophosphamide, doxorubicin (doxorubicin hydrochloride), and rituximab (DA-EPOCH-R) in patients with aggressive, v-myc avian myelocytomatosis viral oncogene homolog (MYC)-aberrant lymphoid malignancies, and to determine the recommended phase II dose (RP2D) of the combination. (Phase I) II. To evaluate the efficacy, as measured by 12-month progression free survival (PFS), of ixazomib given with DA-EPOCH-R in patients with aggressive, MYC-aberrant lymphoid malignancies. (Phase II)
I. Further evaluate the frequency and severity of toxicity. II. Further evaluate the clinical efficacy, as measured by response rate and overall survival (OS).
III. Assess the predictive value of fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) scans on PFS.
I. Determine the impact of cell of origin (COO) upon response rate, PFS, and OS.
II. Assess the feasibility and outcomes of consolidation stem cell transplant (SCT).
OUTLINE: This is a phase I, dose-escalation study of ixazomib citrate followed by a phase II study.
Patients receive ixazomib citrate orally (PO) on day 1 and day 8 or 15; etoposide intravenously (IV), vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO twice daily (BID) on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5.
CENTRAL NERVOUS SYSTEM (CNS) PROPHYLAXIS:
Patients with a negative lumbar puncture (LP) receive methotrexate intrathecally (IT) once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly.
Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year (or as long as deriving benefit) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I-II Trial of DA-EPOCH-R Plus Ixazomib as Frontline Therapy for Patients With MYC-aberrant Lymphoid Malignancies: The DACIPHOR Regimen|
|Study Start Date :||September 2015|
|Estimated Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||July 2020|
Experimental: Treatment (combination chemotherapy, rituximab, ixazomib)
Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5.
Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly.
Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity.
Given IT or intraventricularly
Drug: Doxorubicin Hydrochloride
Drug: Ixazomib Citrate
Other: Laboratory Biomarker Analysis
Given IT or intraventricularly
Drug: Therapeutic Hydrocortisone
Given IT or intraventricularly
Drug: Vincristine Sulfate
- For phase I of the study, the dose-limiting toxicity of ixazomib given with DA-EPOCH-R will be evaluated [ Time Frame: The first 21 days ]The dose-limiting toxicity (DLT), defined as the occurrence of ≥ Grade 3 toxicity experienced during the first cycle (3 weeks or 21 days) of study treatment, will be determined, except for cytopenias. The Maximum Tolerated Dose (MTD) will constitute the RP2D
- For phase II of the study, 12-month PFS (Progression Free Survival) of ixazomib given with DA-EPOCH-R will be measured [ Time Frame: Time elapsed between treatment initiation and tumor progression or death from any cause, assessed at 12 months ]Excluding patients who are lost to follow-up, the 12-month PFS will be defined as the percentage of patients alive and progression free 12 months from start of therapy.
- Frequency of toxicity [ Time Frame: Up to 1 year ]Adverse events will be defined as those included in CTCAE v 4.0. The occurrence of each will be recorded.
- Severity of toxicity [ Time Frame: Up to 1 year ]Adverse events will be defined as those included in CTCAE v 4.0. The severity of each will be recorded.
- Response rate and OS (Overall Survival) [ Time Frame: At 3 weeks and at 6 weeks ]Anti-tumor activity will be defined as the detection of SD (Stable Disease), Partial Response (PR), or CR (Complete Response) by CT or PET/CT scan, and/or resolution of marrow-only involvement. CR and PR will each be assessed according to the Revised Response Criteria for Malignant Lymphoma. Assessments will be performed after cycles 2 and 6, then at the discretion of the treating investigator. OS will be defined as freedom from death by any cause.
- Assess the predictive value of FDG-PET/CT scans on PFS [ Time Frame: Up to 1 year after treatment stopped ]Patients will be categorized as either FDG-PET (+) or (-) at interim and end-of treatment imaging.
- Determine the impact of cell of origin (COO) upon response rate, PFS, and OS [ Time Frame: Up to 1 year ]Impact of COO defined as germinal center B-cell (GCB) and non-GCB via the Hans algorithm upon response rate, PFS, and OS (applicable only to patients with DLBCL).
- Consolidation SCT (Stem cell transplant) [ Time Frame: Up to 1 year ]Feasibility and outcomes of consolidation SCT will be assessed. Patients will be grouped by whether consolidative SCT was performed in first remission, with PFS compared across groups (SCT vs. non-SCT).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02481310
|Contact: Study Coordinator||(312)email@example.com|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Contact: Barbara Pro, MD 312-695-6180|
|Principal Investigator: Barbara Pro, MD|
|United States, Massachusetts|
|Medford, Massachusetts, United States, 02155|
|Contact: Andrew M. Evens, MD 617-636-8077 AEvens@tuftsmedicalcenter.org|
|Principal Investigator: Andrew M. Evens, MD|
|United States, Wisconsin|
|Medical College of Wisconsin||Recruiting|
|Milwaukee, Wisconsin, United States, 53226|
|Contact: Mehdi Hamadani, MD 414-805-0505|
|Principal Investigator: Mehdi Hamadani, MD|
|Principal Investigator:||Barbara Pro, MD||Northwestern University|