Clinical Trial: Combination Chemotherapy, Rituximab, and Ixazomib Citrate in Treating Patients With Non-Hodgkin Lymphoma

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

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

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.

Detailed Summary:

PRIMARY OBJECTIVES:

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)

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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.

INDUCTION:

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 da
Sponsor: Northwestern University

Current Primary Outcome:

  • 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.


Original Secondary Outcome: Same as current

Information By: Northwestern University

Dates:
Date Received: May 26, 2015
Date Started: September 2015
Date Completion:
Last Updated: August 19, 2015
Last Verified: August 2015