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Polatuzumab Vedotin, Venetoclax, and Rituximab and Hyaluronidase Human for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

Primary Purpose

Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Polatuzumab Vedotin
Rituximab
Rituximab and Hyaluronidase Human
Venetoclax
Sponsored by
Academic and Community Cancer Research United
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent B-Cell Non-Hodgkin Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Pathologically confirmed relapsed or primary refractory mantle cell lymphoma with concurrent or prior tissue sample immunohistochemistry (IHC) positive for cyclin D1 or that is positive for fluorescence in situ hybridization (FISH) or cytogenetics for t(11;14)

    • NOTE: Safety Portion only: MCL or indolent B cell non-Hodgkin lymphoma (NHL) (follicular lymphoma [FL] [grades I-IIIa] marginal zone lymphoma [MZL]), or, small lymphocytic lymphoma (SLL) stratified as low risk for tumor lysis syndrome (TLS), relapsed or progressed after at least two lines of therapy (or one BTK inhibitor containing line of therapy). No limit to prior lines of therapy
    • NOTE: Expansion Portion only: MCL relapsed or progressed after at least two lines of therapy or one BTK inhibitor line of therapy. Prior autologous stem cell transplant (AutoSCT) is allowed. No limit to number of prior therapies. May have received prior BTK inhibitor therapy
  • Measurable disease as defined with at least one lesion measuring >= 1 x 1.5 cm
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration)
  • Platelet count >= 75,000/mm^3 (obtained =< 14 days prior to registration)
  • Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration)
  • International normalized ratio =< 1.5 x upper limit of normal (ULN) for patients not receiving therapeutic anticoagulation (obtained =< 14 days prior to registration)
  • Partial thromboplastin time (PTT) or activated PTT (aPTT) =< 1.5 x ULN (obtained =< 14 days prior to registration)
  • Calculated creatinine (Cr) clearance >= 45 ml/min using the modified Cockcroft-Gault formula (obtained =< 14 days prior to registration)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x ULN (obtained =< 14 days prior to registration)
  • Total bilirubin < 1.5 x ULN (or =< 3 x ULN for patients with documented Gilbert syndrome) (obtained =< 14 days prior to registration)
  • Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Able to provide informed written consent, and ability to comply with study related procedures
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
  • Willing to provide tissue samples for mandatory correlative research
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of rituximab and hyaluronidase human, whichever is longer. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:

    • With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose. Men must refrain from donating sperm during this same period.
    • With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose to avoid exposing the embryo

Exclusion Criteria:

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational or chemotherapeutic agent which would be considered as a treatment for the primary neoplasm
  • Known CD20-negative status at relapse or progression
  • Prior allogeneic SCT
  • Completion of autologous SCT =< 100 days prior to registration
  • Radioimmunoconjugate =< 12 weeks prior to registration
  • Monoclonal antibody or antibody-drug conjugate (ADC) therapy within 5 half-lives or 4 weeks prior to registration, whichever is longer
  • Radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to registration (with the exception of ibrutinib to prevent tumor flare, patients taking ibrutinib who are progressing must discontinue ibrutinib 2 half-lives or 2 days prior to initiating protocol therapy)
  • Clinically significant toxicity (other than alopecia) from prior therapy that has not resolved to grade =< 2 (per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0) prior to registration
  • Current grade > 1 peripheral neuropathy
  • Any history of central nervous system (CNS) lymphoma or leptomeningeal infiltration
  • Treatment with systemic corticosteroids > 20 mg/day prednisone or equivalent Patients who are receiving corticosteroids =< 20 mg/day, prednisone or equivalent, for non-lymphoma treatment reasons must be documented to be on a stable dose for at >= 4 weeks prior to registration. If corticosteroid treatment is urgently required for lymphoma symptom control prior to the start of study treatment, up to 100 mg/day of prednisone or equivalent can be given for a maximum of 5 days, but all tumor assessments must be completed prior to start of corticosteroid treatment
  • History of severe allergic or anaphylactic reaction or known sensitivity to humanized or murine monoclonal antibodies rituximab, polatuzumab vedotin, and venetoclax
  • Active bacterial, viral, fungal, or other infection
  • Requirement for warfarin treatment (because of potential drug-drug interactions [DDIs] that may increase the exposure of warfarin)
  • Treatment with the following agents =< 7 days prior to registration

    • Strong and moderate CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin
    • Strong and moderate CYP3A inducers such as rifampin and carbamazepine. If taking proton pump inhibitors willing to avoid co-administration and stagger venetoclax dosing
  • Consumption of grapefruit, grapefruit products, Seville oranges (including marmalade that contains Seville oranges), or star fruit =< 3 days prior to registration
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Active hepatitis B or hepatitis C infection. Patients who have been successfully treated and cleared their virus as evidenced a negative hepatitis (Hep) B or Hep C polymerase chain reaction (PCR) are eligible
  • Known history of human immunodeficiency virus (HIV) positive status or known infection with human T-cell leukemia virus 1. For patients with unknown HIV status, HIV testing will be performed at screening if required by local regulations
  • History of PML (progressive multifocal leukoencephalopathy)
  • Vaccination with a live virus vaccine =< 28 days prior to registration
  • History of other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of the following: curatively treated carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the breast, basal- or squamous-cell skin cancer, stage I melanoma, or low-grade, early-stage localized prostate cancer
  • Any previously treated malignancy that has been in remission without treatment for =< 3 years prior to registration
  • Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)
  • Major surgical procedure other than for diagnosis =< 28 days prior to day 1 of cycle 1, or anticipation of a major surgical procedure during the course of the study
  • Inability or unwillingness to swallow pills
  • History of malabsorption syndrome or other condition that would interfere with enteral absorption
  • History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)

Sites / Locations

  • Mayo Clinic in Arizona
  • Carle Cancer Center NCI Community Oncology Research ProgramRecruiting
  • Iowa-Wide Oncology Research Coalition NCORP
  • Siouxland Regional Cancer CenterRecruiting
  • Michigan Cancer Research Consortium NCORPRecruiting
  • Mayo Clinic in Rochester
  • Washington University School of MedicineRecruiting
  • University of Nebraska Medical Center
  • Laura and Isaac Perlmutter Cancer Center at NYU LangoneRecruiting
  • University of Pennsylvania/Abramson Cancer Center
  • Huntsman Cancer Institute/University of Utah
  • University of Washington Medical Center - Montlake
  • Aurora Cancer Care-Milwaukee

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (rituximab, polatuzumab vedotin, venetoclax)

Arm Description

INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Complete response (CR) rate
Objective status of CR measured by positron emission tomography (PET)-computed tomography (CT) scans according to Lugano 2014.

Secondary Outcome Measures

Overall response rate (ORR)
The ORR at the end of induction will be estimated by the total number of patients who achieve a complete response (CR) or partial response (PR) by PET-CT scans according to Lugano 2014 divided by the total number of evaluable patients. The ORR between ibrutinib-naive and ibrutinib-pretreated patients will be compared using Fisher's exact test.
Best response rate to maintenance therapy
CR, PR, and stable disease (SD) rates for patients who continue to maintenance will be estimated by number of patients who continue on maintenance therapy and achieve CR, PR or SD, respectively, at the end of maintenance divided by the total number of evaluable patients who continue to maintenance.
Progression free survival (PFS)
The distribution of PFS will be estimated using the method of Kaplan-Meier. The PFS between ibrutinib-naive and ibrutinib-pretreated patients will be compared using log-rank test.
Overall survival (OS)
The distribution of OS will be estimated using the method of Kaplan-Meier. The OS between ibrutinib-naive and ibrutinib-pretreated patients will be compared using log-rank test.
Incidence of adverse events (AEs)
All AEs occurring on or after first study treatment will be summarized by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 grade.

Full Information

First Posted
November 19, 2020
Last Updated
September 14, 2023
Sponsor
Academic and Community Cancer Research United
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04659044
Brief Title
Polatuzumab Vedotin, Venetoclax, and Rituximab and Hyaluronidase Human for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
Official Title
A Phase 2 Trial of the Combination of Polatuzumab Vedotin, Venetoclax and Rituximab and Hyaluronidase Human for Relapsed and Refractory Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2021 (Actual)
Primary Completion Date
April 4, 2027 (Anticipated)
Study Completion Date
April 1, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Academic and Community Cancer Research United
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase II trial studies the effect of polatuzumab vedotin, venetoclax, and rituximab and hyaluronidase human in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Polatuzumab vedotin is a monoclonal antibody, polatuzumab, linked to a toxic agent called vedotin. Polatuzumab attaches to CD79B positive cancer cells in a targeted way and delivers vedotin to kill them. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cell growth. Rituximab hyaluronidase is a combination of rituximab and hyaluronidase. Rituximab binds to a molecule called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Hyaluronidase allows rituximab to be given by injection under the skin. Giving rituximab and hyaluronidase by injection under the skin is faster than giving rituximab alone by infusion into the blood. Giving polatuzumab vedotin, venetoclax, and rituximab and hyaluronidase human may work better than standard therapy in treating patients with mantle cell lymphoma.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the end of induction (EOI) complete response rate (CR) for treatment with the regimen of rituximab and hyaluronidase human + polatuzumab vedotin + venetoclax (RSc + Pola + Ven) in relapsed/refractory mantle cell lymphoma (MCL). SECONDARY OBJECTIVES: I. To evaluate the EOI overall response rate (ORR) for the combination of RSc + Pola + Ven in relapsed/refractory MCL. II. To evaluate the best response (CR, partial response [PR]) in patients who continue on to maintenance therapy and evaluate the improvement in the depth of response. III. To evaluate the progression free survival (PFS) and overall survival (OS) for the combination of RSc + Pola + Ven) in relapsed/ refractory MCL. IV. To compare the ORR, CR, PFS, and OS in ibrutinib refractory compared to ibrutinib naive patients. V. To evaluate regimen-related toxicity for patients treated with RSc + Pola + Ven. CORRELATIVE RESEARCH OBJECTIVES: I. To evaluate changes in minimal residual disease (MRD) status in both responding and non-responding patients at EOI and end of maintenance and compared to baseline as well as correlate MRD status with PFS and OS. II. To evaluate changes in systemic immune profiles and T cell activation induced by treatment with RSc + Pola + Ven. III. To evaluate the prognostic importance of high risk cytogenetic alterations, and other risk stratification scores in patients with relapsed/refractory MCL receiving RSc + Pola + Ven. IV. To evaluate features of the tumor microenvironment in patients with relapsed/refractory MCL receiving RSc +Pola+Ven. V. To evaluate molecular features associated with response in PDX models from patients with relapsed/refractory MCL receiving RSc +Pola+Ven. OUTLINE: INDUCTION: Patients receive rituximab intravenously (IV) on day 1 of cycle 1 and rituximab and hyaluronidase human subcutaneously (SC) over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax orally (PO) daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 90 days for up to 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3a Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Refractory Grade 1 Follicular Lymphoma, Refractory Grade 2 Follicular Lymphoma, Refractory Grade 3a Follicular Lymphoma, Refractory Mantle Cell Lymphoma, Refractory Marginal Zone Lymphoma, Refractory Small Lymphocytic Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (rituximab, polatuzumab vedotin, venetoclax)
Arm Type
Experimental
Arm Description
INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Polatuzumab Vedotin
Other Intervention Name(s)
ADC DCDS4501A, Antibody-Drug Conjugate DCDS4501A, DCDS4501A, FCU 2711, polatuzumab vedotin-piiq, Polivy, RG7596, Ro 5541077-000
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
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, Riabni, Rituxan, Rituximab ABBS, Rituximab ARRX, 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 SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, rituximab-abbs, Rituximab-arrx, Rituximab-pvvr, RTXM83, Ruxience, Truxima
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Rituximab and Hyaluronidase Human
Other Intervention Name(s)
Rituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase Human
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Complete response (CR) rate
Description
Objective status of CR measured by positron emission tomography (PET)-computed tomography (CT) scans according to Lugano 2014.
Time Frame
At the end of induction
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
The ORR at the end of induction will be estimated by the total number of patients who achieve a complete response (CR) or partial response (PR) by PET-CT scans according to Lugano 2014 divided by the total number of evaluable patients. The ORR between ibrutinib-naive and ibrutinib-pretreated patients will be compared using Fisher's exact test.
Time Frame
At the end of induction
Title
Best response rate to maintenance therapy
Description
CR, PR, and stable disease (SD) rates for patients who continue to maintenance will be estimated by number of patients who continue on maintenance therapy and achieve CR, PR or SD, respectively, at the end of maintenance divided by the total number of evaluable patients who continue to maintenance.
Time Frame
At the end of maintenance therapy
Title
Progression free survival (PFS)
Description
The distribution of PFS will be estimated using the method of Kaplan-Meier. The PFS between ibrutinib-naive and ibrutinib-pretreated patients will be compared using log-rank test.
Time Frame
From registration to the earliest date of documentation of disease progression by CT or PET/CT or death due to any cause, assessed up to 5 years
Title
Overall survival (OS)
Description
The distribution of OS will be estimated using the method of Kaplan-Meier. The OS between ibrutinib-naive and ibrutinib-pretreated patients will be compared using log-rank test.
Time Frame
From registration to death due to any cause, assessed up to 5 years
Title
Incidence of adverse events (AEs)
Description
All AEs occurring on or after first study treatment will be summarized by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 grade.
Time Frame
Up to 5 years
Other Pre-specified Outcome Measures:
Title
Minimal residual disease (MRD) analysis
Description
MRD status for both responders and non-responders at each time point will be reported descriptively, and explored for correlation with clinical factors and patient outcomes such as PFS and OS.
Time Frame
Up to the end of maintenance therapy
Title
T cell and cytokine subset analysis
Description
Systemic immune profiles and T cell activation will be investigated using multi-parameter flow cytometry, and cytokine analysis in the peripheral blood of patients.
Time Frame
Up to the end of maintenance therapy
Title
High risk cytogenetic alterations
Description
Will be summarized using frequency and percentages.
Time Frame
Up to the end of maintenance therapy
Title
Risk stratification scores
Description
Will be summarized using frequency and percentages.
Time Frame
Up to the end of maintenance therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age >= 18 years Pathologically confirmed relapsed or primary refractory mantle cell lymphoma with concurrent or prior tissue sample immunohistochemistry (IHC) positive for cyclin D1 or that is positive for fluorescence in situ hybridization (FISH) or cytogenetics for t(11;14) NOTE: Safety Portion only: MCL or indolent B cell non-Hodgkin lymphoma (NHL), follicular lymphoma (FL) (grades I-IIIa), marginal-zone lymphoma (MZL) or small lymphocytic lymphoma (SLL) stratified as low risk for tumor lysis syndrome (TLS), relapsed or progressed after at least two lines of therapy, or one line of a BTK inhibitor containing therapy, or Autologous Stem Cell Transplant (AutoSCT). No limit to prior lines of therapy NOTE: Expansion Portion only: MCL relapsed or progressed after at least two lines of therapy, or one line of a BTK inhibitor containing therapy, or Autologous Stem Cell Transplant (AutoSCT). No limit to number of prior therapies. May have received prior BTK inhibitor therapy Measurable disease as defined with at least one lesion measuring >= 1 x 1.5 cm by positron emission tomography (PET)-computed tomography (CT) using Lugano criteria Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration) Platelet count >= 75,000/mm^3 (obtained =< 14 days prior to registration) Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration) International normalized ratio =< 1.5 x upper limit of normal (ULN) for patients not receiving therapeutic anticoagulation (obtained =< 14 days prior to registration) Partial thromboplastin time (PTT) or activated PTT (aPTT) =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (obtained =< 14 days prior to registration) Total bilirubin < 1.5 x ULN (or =< 3 x ULN for patients with documented Gilbert syndrome) (obtained =< 14 days prior to registration) Calculated creatinine (Cr) clearance >= 45 ml/min using the modified Cockcroft-Gault formula (obtained =< 14 days prior to registration) Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only NOTE: A female of childbearing potential is a sexually mature female who: Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months) Able to provide informed written consent, and ability to comply with study related procedures Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) Willing to provide tissue samples for mandatory correlative research For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of rituximab and hyaluronidase human, whichever is longer. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose. Men must refrain from donating sperm during this same period. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose to avoid exposing the embryo Exclusion Criteria: Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Receiving any other investigational or chemotherapeutic agent which would be considered as a treatment for the primary neoplasm Known CD20-negative status at relapse or progression Prior allogeneic SCT Completion of autologous SCT =< 100 days prior to registration Treatment with radioimmunoconjugate =< 12 weeks prior to registration Monoclonal antibody or antibody-drug conjugate (ADC) therapy within 5 half-lives or 4 weeks prior to registration, whichever is longer Radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to registration (with the exception of ibrutinib to prevent tumor flare, patients taking ibrutinib who are progressing must discontinue ibrutinib 2 half-lives or 2 days prior to initiating protocol therapy) Clinically significant toxicity (other than alopecia) from prior therapy that has not resolved to grade =< 2 (per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0) prior to registration Current grade > 1 peripheral neuropathy Any history of central nervous system (CNS) lymphoma or leptomeningeal infiltration Treatment with systemic corticosteroids > 20 mg/day prednisone or equivalent Patients who are receiving corticosteroids =< 20 mg/day, prednisone or equivalent, for non-lymphoma treatment reasons must be documented to be on a stable dose for >= 4 weeks prior to registration. If corticosteroid treatment is urgently required for lymphoma symptom control prior to the start of study treatment, up to 100 mg/day of prednisone or equivalent can be given for a maximum of 5 days, but all tumor assessments must be completed prior to start of corticosteroid treatment History of severe allergic or anaphylactic reaction or known sensitivity to humanized or murine monoclonal antibodies rituximab, polatuzumab vedotin, or venetoclax Active bacterial, viral, fungal, or other infection Requirement for warfarin treatment (because of potential drug-drug interactions [DDIs] that may increase the exposure of warfarin) Treatment with the following agents =< 7 days prior to registration Strong and moderate CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin Strong and moderate CYP3A inducers such as rifampin and carbamazepine. If subject is taking proton pump inhibitors, subject is willing to avoid co-administration and stagger venetoclax dosing Consumption of grapefruit, grapefruit products, Seville oranges (including marmalade that contains Seville oranges), or star fruit =< 3 days prior to registration Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis Active hepatitis B or hepatitis C infection NOTE: Patients who have been successfully treated and cleared their virus as evidenced by a negative hepatitis (Hep) B or Hep C polymerase chain reaction (PCR) are eligible Known history of human immunodeficiency virus (HIV) positive status or known infection with human T-cell leukemia virus 1. For patients with unknown HIV status, HIV testing will be performed at screening History of PML (progressive multifocal leukoencephalopathy) Vaccination with a live virus vaccine =< 28 days prior to registration History of other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of the following: curatively treated carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the breast, basal- or squamous-cell skin cancer, stage I melanoma, or low-grade, early-stage localized prostate cancer Any previously treated malignancy that has been in remission without treatment for =< 3 years prior to registration Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm) Major surgical procedure other than for diagnosis =< 28 days prior to day 1 of cycle 1, or anticipation of a major surgical procedure during the course of the study Inability or unwillingness to swallow pills History of malabsorption syndrome or other condition that would interfere with enteral absorption History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine S Diefenbach
Organizational Affiliation
Academic and Community Cancer Research United
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Individual Site Status
Withdrawn
Facility Name
Carle Cancer Center NCI Community Oncology Research Program
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tyler J. Martin
Phone
217-326-4502
Email
tyler.martin@carle.com
First Name & Middle Initial & Last Name & Degree
Suparna Mantha
Facility Name
Iowa-Wide Oncology Research Coalition NCORP
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50309
Country
United States
Individual Site Status
Withdrawn
Facility Name
Siouxland Regional Cancer Center
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51101
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ACCRU Operations
Phone
507-538-7448
Email
ACCRU@mayo.edu
First Name & Middle Initial & Last Name & Degree
Donald B. Wender
Facility Name
Michigan Cancer Research Consortium NCORP
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ACCRU Operations
Phone
507-538-7448
Email
ACCRU@mayo.edu
First Name & Middle Initial & Last Name & Degree
Tareq Al Baghdadi
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Withdrawn
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ACCRU Operations
Phone
507-538-7448
Email
ACCRU@mayo.edu
First Name & Middle Initial & Last Name & Degree
Brad S. Kahl
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Individual Site Status
Withdrawn
Facility Name
Laura and Isaac Perlmutter Cancer Center at NYU Langone
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ACCRU Operations
Phone
507-538-7448
Email
ACCRU@mayo.edu
First Name & Middle Initial & Last Name & Degree
Catherine S. Diefenbach
Facility Name
University of Pennsylvania/Abramson Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Castillo
Phone
216-614-1846
Email
Jeniffer.Castillo@uphs.upenn.edu
First Name & Middle Initial & Last Name & Degree
Jakub Svoboda
Facility Name
Huntsman Cancer Institute/University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Withdrawn
Facility Name
University of Washington Medical Center - Montlake
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Individual Site Status
Withdrawn
Facility Name
Aurora Cancer Care-Milwaukee
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53209
Country
United States
Individual Site Status
Withdrawn

12. IPD Sharing Statement

Learn more about this trial

Polatuzumab Vedotin, Venetoclax, and Rituximab and Hyaluronidase Human for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

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