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Combination Chemotherapy, Rituximab, and Ixazomib Citrate in Treating Patients With Non-Hodgkin Lymphoma
||A Phase I-II Trial of DA-EPOCH-R Plus Ixazomib as Frontline Therapy for Patients With MYC-aberrant Lymphoid Malignancies: The DACIPHOR Regimen
Burkitt Lymphoma, Non-Hodgkin Lymphoma
||Andreas Klein, MD
The purpose of this study is to evaluate the effects, good and bad of a new drug called ixazomib (also called MLN9708), when it is given along with a common treatment combination, called Dose-Adjusted EPOCH-R (DA-EPOCH-R, for short). This is a type of study called a phase I/II trial. In the phase I part, the dose of the study drug (ixazomib) will be adjusted (either up or down) to find the maximum (highest) dose that does not cause excessive (too many) harmful side effects. In the phase II part, this dose of ixazomib will be given at the maximum safe dose found in phase I. In both phase I and II, DA-EPOCH-R will be adjusted between cycles depending on how blood cell levels are affected between cycles. Ixazomib is considered investigational because it is not approved by the U.S. Food and Drug Administration (FDA). DA-EPOCH-R is a combination chemotherapy treatment developed over the last 14-15 years, and each of the drugs in this regimen is FDA-approved and considered part of the standard of care.
- Patients must have a histological diagnosis of any of the following (all stages allowed):
- Diffuse large b-cell lymphoma (DLBCL) (including transformation from a previously indolent non-Hodgkin lymphoma [NHL], so long as no prior systemic treatment was given for the indolent NHL)
- B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma
- Burkitt lymphoma
- MYC+ plasmablastic lymphoma by histology
- Patients must have measurable disease (defined as >= 1.5 cm in diameter)
- Patients must have MYC-rearrangement, as determined by fluorescent in-situ hybridization (FISH) (does not require central review)
- Patients who have had more than one cycle of prior chemoimmunotherapy for diagnosis of NHL are not eligible; NOTE: such patients must have fully recovered (ie, =< grade 1 toxicity) from the reversible effects of prior chemotherapy before starting treatment on the current protocol
- Patients who have had major surgery within 4 weeks prior to registration are not eligible
- Patients who have had radiotherapy within 14 days before registration are not eligible; NOTE: If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
Induction therapy will consist of 6 cycles of combination DA-EPOCH-R with ixazomib. During induction treatment, ixazomib will be given twice per cycle (1 cycle = 21 days during induction); the first dose will be given on day 1 and the second on either day 8 or 15.
Patients who do not go on to be treated with consolidative SCT will be treated with maintenance ixazomib for up to 1 year (or longer for continued clinical benefit with documented approval from Takeda, the PI, and DMC. Similar to induction, maintenance with uninterrupted ixazomib may not be well-tolerated; therefore during maintenance treatment, ixazomib 4 mg will be given days 1, 8, and 15 of each cycle (1 cycle = 28 days during maintenance), and no drug will be given on day 22.
CBC and Chem panels will be done throughout the study. Optional blood banking at the start of induction and maintenance cycle.