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A Randomized 3-Arm Phase II Study Comparing 1.) Bendamustine, Rituximab and High Dose Cytarabine (BR / CR) 2.) Bendamustine, Rituximab, High Dose Cytarabine and Acalabrutinib (BR / CR-A), and 3.) Bendamustine, Rituximab and Acalabrutinib (BR-A) in Patients < / = 70 years Old with Untreated Mantle Cell Lymphoma

Status
Active
Cancer Type
Trial Phase
Phase II
Eligibility
18 - 70 Years, Male and Female
Study Type
Treatment
NCT ID
NCT04115631
Protocol IDs
EA4181 (primary)
EA4181
NCI-2019-05536
Study Sponsor
ECOG-ACRIN Cancer Research Group

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 intravenously (IV) on days 1 and 2 and rituximab IV 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 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 IV on days 1 and 2, and rituximab IV 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 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 IV on days 1 and 2, and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years, and then every 6 months 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

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.
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