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

NCT04659044 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: ACCRU-LY-1806NCI-2020-08188P30CA015083
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of Patients Experiencing a Complete Response (CR)

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

  3 months

Secondary Outcomes (5)

• Overall Response Rate (ORR)

  3 months

• Best Response Rate to Maintenance Therapy

  At the end of maintenance therapy

• Progression Free Survival (PFS)

  10 months

• Overall Survival (OS)

  15 months

• Count of Patients Experiencing Grade 3+ Adverse Events (AEs)

  15 months

Other Outcomes (4)

• Minimal Residual Disease (MRD) Analysis

  Up to the end of maintenance therapy

• T Cell and Cytokine Subset Analysis

  Up to the end of maintenance therapy

• High Risk Cytogenetic Alterations

  Up to the end of maintenance therapy

Study Arms (1)

Treatment (rituximab, polatuzumab vedotin, venetoclax)

EXPERIMENTAL

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.

Drug: Polatuzumab Vedotin; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human; Drug: Venetoclax

Interventions

Polatuzumab Vedotin DRUG

Given IV

Also known as: ADC DCDS4501A, Antibody-Drug Conjugate DCDS4501A, DCDS4501A, FCU 2711, polatuzumab vedotin-piiq, Polivy, RG7596, Ro 5541077-000

Treatment (rituximab, polatuzumab vedotin, venetoclax)

Rituximab BIOLOGICAL

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, 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

Treatment (rituximab, polatuzumab vedotin, venetoclax)

Rituximab and Hyaluronidase Human BIOLOGICAL

Given SC

Also known as: Rituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase Human

Treatment (rituximab, polatuzumab vedotin, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (rituximab, polatuzumab vedotin, venetoclax)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Siouxland Regional Cancer Center

Sioux City, Iowa, 51101, United States

Location

Michigan Cancer Research Consortium NCORP

Ann Arbor, Michigan, 48106, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

polatuzumab vedotin; Rituximab; CT-P10; Hyaluronoglucosaminidase; venetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases

Results Point of Contact

• Title: Catherine Diefenbach M.D.
• Organization: Perlmutter Cancer Center at NYU Langone Health

Catherine.diefenbach@nyulangone.org

(212) 731-5670

Study Officials

• Catherine S Diefenbach

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2020
• First Posted: December 9, 2020
• Study Start: April 1, 2021
• Primary Completion: March 28, 2024
• Study Completion: March 29, 2024
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Locations

US (5)