Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Criteria


Inclusion Criteria:

- 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).

- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial.

- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated.

- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load.

- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial.

- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional classification. To be
eligible for this trial, patients should be class 2B or better.

- Patients must have a QT interval (QTc) =< 480 msec obtained within 14 days of
randomization.

- Women must not be pregnant or breast-feeding due to the potential harm to an unborn
fetus and possible risk for adverse events in nursing infants with the treatment
regimens being used. Patients must also not expect to conceive or father children from
the time of registration, while on study treatment, and until 12 months after the last
dose of study treatment. All females of childbearing potential must have a blood test
or urine study within 2 weeks prior to randomization to rule out pregnancy. A female
of childbearing potential is any woman, regardless of sexual orientation or whether
they have undergone tubal ligation, who meets the following criteria: has achieved
menarche at some point, has not undergone a hysterectomy or bilateral oophorectomy; or
has not been naturally postmenopausal (amenorrhea following cancer therapy does not
rule out childbearing potential) for at least 24 consecutive months (i.e., has had
menses at any time in the preceding 24 consecutive months).

- Women of childbearing potential and sexually active males must agree to use accepted
and effective method(s) of contraception or to abstain from sexual intercourse for the
duration of their participation in the study and for 12 months after treatment ends.

- Patients are not eligible if they require treatment with a strong cytochrome P450
(CYP) 3A inhibitor.

- Patients may not have received the following within 7 days prior to the first dose of
study drug:

- Strong and moderate CYP3A inhibitors

- Strong and moderate CYP3A inducers

- Patients are ineligible if they have any of the following:

- Malabsorption syndrome or disease significantly affecting gastrointestinal
function.

- Active bleeding or history of bleeding diathesis (e.g. hemophilia or von
Willebrand disease).

- Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic
thrombocytopenia purpura).

- Requires or receiving anticoagulation with warfarin or equivalent vitamin K
antagonists (e.g. phenprocoumon) within 7 days of first dose of study drug.

- History of significant cerebrovascular disease/event, including stroke or
intracranial hemorrhage, within 6 months before the first dose of study drug.

- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other
infections at study enrollment (defined as exhibiting ongoing signs/symptoms
related to the infection and without improvement, despite appropriate antibiotics
or other treatment).

- History of severe allergic reaction attributed to compounds of similar chemical
or biologic composition to rituximab, bendamustine, cytarabine, or acalabrutinib.

- Patients must be able to fulfill one of the following eligibility requirements
pertaining to biospecimen availability for submission following randomization:

- Archived formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen from the
original diagnostic biopsy is available for submission OR,

- If tumor tissue is not available, peripheral blood collected prior to initiation
of protocol therapy will be submitted

- NOTE: Biospecimens must be submitted within 60 days following randomization
to Adaptive Biotechnologies for ClonoSEQ ID molecular marker identification
of unique clonal immunoglobulin deoxyribonucleic acid (DNA) sequence. If
peripheral blood will be submitted, Adaptive Biotechnologies should be
contacted prior to patient randomization for guidance pertaining to
collection and submission requirements.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A (bendamustine, rituximab, cytarabine)
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: Bendamustine
    Given IV
    Other names:
    • SDX-105
  • Drug: Bendamustine Hydrochloride
    Given IV
    Other names:
    • Bendamustin Hydrochloride
    • Bendeka
    • Cytostasan Hydrochloride
    • Levact
    • Ribomustin
    • SyB L-0501
    • Treanda
  • Drug: Cytarabine
    Given IV
    Other names:
    • .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
  • Biological: Rituximab
    Given IV
    Other names:
    • 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
Experimental
Arm B (acalabrutinib, bendamustine, rituximab, cytarabine)
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: Acalabrutinib
    Given PO
    Other names:
    • ACP-196
    • Bruton Tyrosine Kinase Inhibitor ACP-196
    • Calquence
  • Drug: Bendamustine
    Given IV
    Other names:
    • SDX-105
  • Drug: Bendamustine Hydrochloride
    Given IV
    Other names:
    • Bendamustin Hydrochloride
    • Bendeka
    • Cytostasan Hydrochloride
    • Levact
    • Ribomustin
    • SyB L-0501
    • Treanda
  • Drug: Cytarabine
    Given IV
    Other names:
    • .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
  • Biological: Rituximab
    Given IV
    Other names:
    • 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
Experimental
Arm C (acalabrutinib, bendamustine, rituximab)
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: Acalabrutinib
    Given PO
    Other names:
    • ACP-196
    • Bruton Tyrosine Kinase Inhibitor ACP-196
    • Calquence
  • Drug: Bendamustine
    Given IV
    Other names:
    • SDX-105
  • Drug: Bendamustine Hydrochloride
    Given IV
    Other names:
    • Bendamustin Hydrochloride
    • Bendeka
    • Cytostasan Hydrochloride
    • Levact
    • Ribomustin
    • SyB L-0501
    • Treanda
  • Biological: Rituximab
    Given IV
    Other names:
    • 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

Recruiting Locations

University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
Contact:
Site Public Contact
913-588-3671
KUCC_Navigation@kumc.edu

University of Kansas Cancer Center
Kansas City, Kansas 66160
Contact:
Site Public Contact
913-588-3671
KUCC_Navigation@kumc.edu

University of Kansas Cancer Center - North
Kansas City, Missouri 64154
Contact:
Site Public Contact
913-588-3671
KUCC_Navigation@kumc.edu

University of Kansas Cancer Center-Overland Park
Overland Park, Kansas 66210
Contact:
Site Public Contact
913-588-3671
KUCC_Navigation@kumc.edu

University of Kansas Health System Saint Francis Campus
Topeka, Kansas 66606
Contact:
Site Public Contact
785-295-8000

More Details

Status
Recruiting
Sponsor
ECOG-ACRIN Cancer Research Group

Study Contact

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.