NCT04115631|Active Not RecruitingPhase 2DMCFDA Drug

A Comparison of Three Chemotherapy Regimens for the Treatment of Patients With Newly Diagnosed Mantle Cell Lymphoma

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

ECOG-ACRIN Cancer Research Group ClinicalTrials.gov

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3 other identifiers

EA4181NCI-2019-05536U10CA180820

Study Type

interventional

Target

360

Locations

1 country

Sites

504

Timeline

RegisteredOct 2019

StartedDec 2019

CompletionDec 2026

Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

360

participants targeted

Target at P75+ for phase_2

Timeline

8mo left

Started Dec 2019

Longer than P75 for phase_2

Geographic Reach

1 country

504 active sites

Status

active not recruiting

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

7.1 years study duration

Study Progress91%

Dec 2019Dec 2026

First Submitted

Initial submission to the registry

September 6, 2019

Completed

28 days until next milestone

First Posted

Study publicly available on registry

October 4, 2019

Completed

2 months until next milestone

Study Start

First participant enrolled

December 13, 2019

Completed

7.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Last Updated

May 5, 2026

Status Verified

April 1, 2026

Enrollment Period

7.1 years

First QC Date

September 6, 2019

Last Update Submit

April 29, 2026

Conditions

Liver Lymphoma Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

Composite of positron emission tomography (PET)/computed tomography (CT) complete response (CR) and peripheral blood (PB) minimal residual disease (MRD) negative rate
MRD status is defined as positive, negative, or indeterminate as measured from PB specimens following completion of treatment. Measures of frequencies and proportion, and location and dispersion will be used to describe categorical, and continuous variables respectively; 90% confidence intervals around these estimates will be computed. Kaplan-Meier method will be used to describe time-to-event endpoints and log-rank test to assess difference in time-to-event endpoints by levels of a categorical predictor. Cox proportional hazards (PH) regression model would be used to model the impact of baseline and other relevant variables on time-to-event endpoints.
Up to 8 weeks post treatment

Secondary Outcomes (5)

Progression-free survival (PFS)
From randomization to earliest of disease progression or death, assessed at 36 months
Incidence of adverse events
Up to 10 years post randomization
Objective response rate (ORR)
Up to 10 years post randomization
Overall survival (OS)
From randomization to death, assessed at 36 months
Mobilization failure rate
Up to 10 years post randomization

Other Outcomes (8)

PET/CT negative rate between the three arms
Up to 10 years post randomization
PET quantitative assessment (qPET)
At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Change of qPET parameters
Baseline to end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
+5 more other outcomes

Study Arms (3)

Arm A (bendamustine, rituximab, cytarabine)

EXPERIMENTAL

Patients receive 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 rituximab IV on day 1 and cytarabine IV every 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.

Drug: BendamustineDrug: Bendamustine HydrochlorideDrug: CytarabineBiological: Rituximab

Arm B (acalabrutinib, bendamustine, rituximab, cytarabine)

EXPERIMENTAL

Patients receive 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 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.

Drug: AcalabrutinibDrug: BendamustineDrug: Bendamustine HydrochlorideDrug: CytarabineBiological: Rituximab

Arm C (acalabrutinib, bendamustine, rituximab)

EXPERIMENTAL

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.

Drug: AcalabrutinibDrug: BendamustineDrug: Bendamustine HydrochlorideBiological: Rituximab

Interventions

RituximabBIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima

Arm A (bendamustine, rituximab, cytarabine)Arm B (acalabrutinib, bendamustine, rituximab, cytarabine)Arm C (acalabrutinib, bendamustine, rituximab)

AcalabrutinibDRUG

Given PO

Also known as: ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence

Arm B (acalabrutinib, bendamustine, rituximab, cytarabine)Arm C (acalabrutinib, bendamustine, rituximab)

BendamustineDRUG

Given IV

Also known as: SDX-105

Arm A (bendamustine, rituximab, cytarabine)Arm B (acalabrutinib, bendamustine, rituximab, cytarabine)Arm C (acalabrutinib, bendamustine, rituximab)

Bendamustine HydrochlorideDRUG

Given IV

Also known as: Bendamustin Hydrochloride, Bendeka, Cytostasan Hydrochloride, Levact, Ribomustin, SyB L-0501, Treanda

Arm A (bendamustine, rituximab, cytarabine)Arm B (acalabrutinib, bendamustine, rituximab, cytarabine)Arm C (acalabrutinib, bendamustine, rituximab)

CytarabineDRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Arm A (bendamustine, rituximab, cytarabine)Arm B (acalabrutinib, bendamustine, rituximab, cytarabine)

Eligibility Criteria

Age18 Years - 70 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Baseline measurements and evaluations must be obtained within 6 weeks of randomization to the study. Abnormal PET or CT scans may constitute evaluable disease. Patient must have at least one objective measurable disease parameter. Measurable disease in the liver is required if the liver is the only site of lymphoma.
MIPI score must be calculated and entered in Oncology Patient Enrollment Network (OPEN).
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
Patients must have untreated histologically confirmed mantle cell lymphoma, with cyclin D1 (BCL1) expression by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescent in situ hybridization (FISH). The diagnosis must be confirmed by formal hematopathology review at the enrolling center.
Patients being treated with gastric reducing agents proton pump inhibitors must be switched to an alternative drug before starting acalabrutinib.
Absolute neutrophil count (ANC) \>= 1,000/mcL (obtained with 14 days of randomization). If disease includes marrow involvement or hypersplenism, please reference the below revised ANC requirement:
ANC \>= 500/mcL
Platelets \>= 75,000 mcL (obtained with 14 days of randomization). If disease includes involvement or hypersplenism, please reference the below revised platelet requirement:
Platelets \>= 25,000/mcL
Total bilirubin =\< 2 x institutional upper limit of normal (ULN) (obtained with 14 days of randomization). If disease includes hepatic infiltration or is causing biliary obstruction, or if elevated bilirubin is due to Gilbert's disease, please reference the below revised bilirubin requirements:
Bilirubin =\< 3 x institutional ULN
Aspartate aminotransferase (AST) and alanine transaminase (ALT) =\< 2.5 x institutional ULN (obtained with 14 days of randomization). If disease includes hepatic infiltration or is causing biliary obstruction, or if elevated bilirubin is due to Gilbert's disease, please reference the below revised AST/ALT requirements:
AST/ALT =\< 5 x institutional ULN
Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (aPTT) in the absence of lupus anticoagulant) \< 2 x institutional ULN (obtained with 14 days of randomization). Patients receiving anticoagulant therapy (other than warfarin or equivalent vitamin K antagonists which are excluded), higher INR/aPTT may be permitted to enroll to this study after discussion with the primary investigator (PI).
Creatinine =\< institutional ULN, OR glomerular filtration rate (GFR) \>= 40 mL/min/1.73 m\^2 (obtained with 14 days of randomization).
+24 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

ECOG-ACRIN Cancer Research Grouplead
National Cancer Institute (NCI)collaborator

Study Sites (504)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC