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A Comparison of Three Chemotherapy Regimens for Patients with Newly Diagnosed Mantle Cell Lymphoma


Active: No
Cancer Type: Hematopoietic Malignancies
Lymphoma
Non-Hodgkin Lymphoma
Unknown Primary
NCT ID: NCT04115631
Trial Phases: Phase II Protocol IDs: EA4181 (primary)
NCI-2019-05536
EA4181
Eligibility: 18 - 70 Years, Male and Female Study Type: Treatment
Study Sponsor: ECOG-ACRIN Cancer Research Group
NCI Full Details: http://clinicaltrials.gov/show/NCT04115631

Summary

This phase II trial compares three chemotherapy regimens consisting of bendamustine, rituximab, high dose cytarabine, and acalabrutinib and studies how well they work in treating patients with newly diagnosed mantle cell lymphoma. Drugs used in chemotherapy, such as bendamustine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This study is being done to find out if one the drug combinations of bendamustine, rituximab, high dose cytarabine, and acalabrutinib is better or worse than the usual approach for mantle cell lymphoma.

Objectives

PRIMARY OBJECTIVE:
I. Positron mission tomography (PET)/computed tomography (CT) complete response (CR)/peripheral blood minimal residual disease (MRD) negative rate.

SECONDARY OBJECTIVES:
I. Progression-free survival at 36 months.
II. Toxicity rates (incidence of grade 3/4 infections, renal and neurologic toxicities, cumulative dose of cytarabine & acalabrutinib, dose reduction, and treatment discontinuation due to toxicity).
III. Objective response rate (ORR).
IV. Overall survival at 36 months.
V. Mobilization failure rate (defined as a yield < 2 x 10^6 CD34+ stem cells/kg with a maximum of 4 courses of apheresis).
VI. To compare PET/CT negative rate between the three arms.
VII. To evaluate the association between baseline PET quantitative assessment (qPET) and MRD status at end of treatment (EOT).
VIII. To evaluate the association between the change of qPET parameters from baseline to EOT and MRD, and compare this association across all 3 arms.
IX. To determine the incremental prognostic value of baseline qPET to standard risk markers (Mantle Cell Lymphoma International Prognostic Index [MIPI]) in predicting MRD status at EOT.
X. To determine the prognostic value of baseline, interim and EOT PET in predicting progression-free survival (PFS).

EXPLORATORY IMAGING OBJECTIVES:
I. Interim PET status both qualitatively (Deauville) and quantitatively will be correlated with MRD status at EOT (end of induction).
II. Explore the incremental prognostic value of interim qPET to standard risk markers (MIPI) in predicting MRD status at EOT.
III. Explore the incremental prognostic value of interim qPET to Ki67 in predicting MRD status at EOT.
IV. Explore the association of interim and EOT PET with overall survival (OS).

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive bendamustine hydrochloride intravenously (IV) on days 1 and 2 and rituximab IV or rituximab and hyaluronidase human subcutaneously (SC) on day 1 or 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients receive rituximab IV or rituximab and hyaluronidase human SC on day 1 and cytarabine IV every 12 hours (Q12 hours) on days 1 and 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28, bendamustine hydrochloride IV on days 1 and 2, and rituximab IV or rituximab and hyaluronidase human SC on day 1 or 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients receive acalabrutinib PO BID on days 1-7 and 22-28, rituximab IV or rituximab and hyaluronidase human SC on day 1, and cytarabine IV Q12 hours on days 1 and 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive acalabrutinib PO BID on days 1-28, bendamustine hydrochloride IV on days 1 and 2, and rituximab IV or rituximab and hyaluronidase human SC on day 1 or 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients in all arms undergo PET/CT scans throughout the trial, CT scans during follow up, and collection of blood samples throughout the trial.

After completion of study treatment, patients are followed up every 2-3 months for years 1-3, and then every 6 months for years 4-5, and then annually until year 10.

Treatment Sites in Georgia

Emory Saint Joseph's Hospital
5665 Peachtree Dunwoody Road NE
Atlanta, GA 30342
www.emoryhealthcare.org



Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

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