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
5 other identifiers
interventional
38
1 country
5
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Oct 2015
Longer than P75 for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 26, 2015
CompletedFirst Posted
Study publicly available on registry
June 25, 2015
CompletedStudy Start
First participant enrolled
October 28, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 26, 2020
CompletedResults Posted
Study results publicly available
December 8, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2024
CompletedFebruary 21, 2022
February 1, 2022
4.9 years
May 26, 2015
September 13, 2021
February 17, 2022
Conditions
Outcome Measures
Primary Outcomes (2)
To Determine the Recommended Phase II Dose (RP2D) of Ixazomib in Combination With DA-EPOCH-R.
The RP2D will be determined by the evaluation of dose-limiting toxicities (DLT) to find the Maximum Tolerated Dose (MTD) which will constitute the RP2D. DLTs will be 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 dose of ixazomib will start at 2.3 mg weekly (for phase I patients) when given concurrently with DA-EPOCH-R. Single-subject cohorts (escalating in ixazomib dose) will be enrolled until the MTD is encountered, after which expansion to 3-subject cohorts will be undertaken. The MTD from phase I will equate the RP2D for ixazomib given in conjunction with DA-EPOCH-R.
The first 21 days of treatment
12-month PFS (Progression Free Survival) of Treatment With Ixazomib in Combination With DA-EPOCH-R (Phase II)
12-month PFS will be defined as the percentage of patients alive and progression free 12 months from start of therapy. Patients lost to follow up will be censored from last point of contact. PFS was calculated using a Kplan-meier estimation with the probability of patients being progression free at 12 months, presented as the percentage based on this probability.
Up to 12 months from initiation of treatment
Secondary Outcomes (4)
Toxicity of Treatment With Ixazomib in Combination With DA-EPOCH-R
Assessed at the beginning each cycle with up to 6 cycles of induction treatment and up to 13 cycles of maintenance treatment (1 cycle =21 days) and at approximately 21 days after the last treatment.
Overall Survival (OS)
Up to approximately 30 months
Response Rate
After 2 cycles, then after 6 cycles and then at the discretion of the investigator for up to 13 maintenance cycles (1 cycle = 21 days)
Assess the Predictive Value of FDG-PET/CT Scans on PFS
Up to 1 year after treatment stopped
Other Outcomes (2)
Determine the Impact of Cell of Origin (COO) Upon Response Rate, PFS, and OS
Up to 1 year
Consolidation SCT (Stem Cell Transplant)
Up to 1 year
Study Arms (1)
Treatment (combination chemotherapy, rituximab, ixazomib)
EXPERIMENTALINDUCTION: 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. CNS PROPHYLAXIS: 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. MAINTENANCE: 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.
Interventions
Given IV
Given IT or intraventricularly
Given IV
Given IV
Given PO
Correlative studies
Given IT or intraventricularly
Given PO
Given IV
Given IT or intraventricularly
Given IV
Eligibility Criteria
You may qualify if:
- 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)
- The following results must be available or pending at time of registration, though results will not affect enrollment/treatment:
- B-cell chronic lymphocytic leukemia (CLL)/lymphoma (BCL)-2 rearrangement by FISH
- BCL-6 rearrangement by FISH NOTE: although not required, it is encouraged that MYC and BCL-2 be measured by immunohistochemistry (IHC) and clearly documented
- Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
- Absolute neutrophil count (ANC) \>= 1,000/mm\^3
- Platelets \>= 75,000/mm\^3
- Total bilirubin =\< 1.5 x upper limit of normal (ULN); NOTE: exceptions can be granted from principal investigator (PI) for instances of Gilbert's disease, and/or primarily indirect bilirubinemia, if due to recent transfusion and/or hemolysis
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SPGT\]) =\< 3 X institutional ULN
- +12 more criteria
You may not qualify if:
- 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
- Patients who have an infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment are not eligible
- Patients who have evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months are not eligible
- Patients who have undergone systemic treatment, within 14 days prior to registration, with strong inhibitors of cytochrome P450 superfamily (CYP)1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort are not eligible
- Patients who have a clinically active hepatitis B or C virus infection are not eligible; NOTE: those with evidence of exposure to hepatitis B virus (HBV) may enroll so long as HBV viral load is negative AND subject is willing/able to take appropriate antiviral prophylaxis to prevent reactivation
- Patients with any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol are not eligible
- Patients who have a known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent are not eligible
- Patients who have a known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing are not eligible
- Patients who have been diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease are not eligible; NOTE: Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
- Patients who have \>= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period are not eligible
- Patients who are participating in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of registration and throughout the duration of this trial are not eligible
- Female patients who are nursing or have a positive pregnancy test during screening are not eligible
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Northwestern Universitylead
- National Cancer Institute (NCI)collaborator
- Millennium Pharmaceuticals, Inc.collaborator
Study Sites (5)
Northwestern University
Chicago, Illinois, 60611, United States
Tufts University
Medford, Massachusetts, 02155, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901, United States
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (1)
Karmali R, Galvez C, Hamadani M, Gordon L, Winter J, Ma S, Nelson V, Fenske TS, Shah NN, Jagadeesh D, Klein A, Helenowski I, Chen R, Mi X, Petrich A, Evens AM, Pro B. A phase 1-2 trial of DA-EPOCH-R plus ixazomib for MYC-aberrant lymphoid malignancies: the DACIPHOR regimen. Blood Adv. 2024 Apr 9;8(7):1612-1620. doi: 10.1182/bloodadvances.2023011369.
PMID: 38237077DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The study closed accrual prior to the planned sample size being enrolled and treated on the study.
Results Point of Contact
- Title
- Barbara Pro, MD
- Organization
- Northwestern University
Study Officials
- PRINCIPAL INVESTIGATOR
Barbara Pro, MD
Northwestern University
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 26, 2015
First Posted
June 25, 2015
Study Start
October 28, 2015
Primary Completion
September 26, 2020
Study Completion
July 1, 2024
Last Updated
February 21, 2022
Results First Posted
December 8, 2021
Record last verified: 2022-02