Study of PV in Combination With Bendamustine and Rituximab for Patients With R/R MCL

NCT04913103 | Not Yet Recruiting Phase 2

• 1 other identifier: CLSG-MCL-POLA
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 7

Brief Summary

A Czech Lymphoma Study Group, phase II, open-label, study of polatuzumab-vedotin in combination with bendamustine and rituximab for patients with mantle cell lymphoma, who relapse after previous therapy with Bruton tyrosine kinase inhibitor

Conditions

Lymphoma, Mantle-Cell

Keywords

refractory/relapsed mantle cell lymphoma; polatuzumab-vedotin; bendamustine; rituximab

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  evaluation of the efficacy of the combination of polatuzumab vedotin plus bendamustine and rituximab (BR) with respect to progression-free survival (PFS)

  4 years

Secondary Outcomes (4)

• overall response rate (ORR)

  4 years

• duration of response (DoR)

  4 years

• event free survival (EFS)

  4 years

• overall survival (OS)

  4 years

Study Arms (1)

single arm, open-label

EXPERIMENTAL

combination of polatuzumab-vedotin, bendamustine and rituximab

Drug: Polatuzumab vedotin; Drug: Bendamustine Hydrochloride; Drug: Rituximab

Interventions

Polatuzumab vedotin DRUG

treatment by a study drug polatuzumab-vedotin, i.v.

Also known as: Polivy

single arm, open-label

Bendamustine Hydrochloride DRUG

treatment by a study drug bendamustin i.v.

Also known as: Bendamustine Accord, Bendamustine Glenmark, Bendamustine KABI

single arm, open-label

Rituximab DRUG

treatment by a study drug rituximab, i.v.

Also known as: Mabthera, Rixathon, Truxima

single arm, open-label

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written Informed Consent Form
• Adult patients with relapsed or refractory MCL after failure of BTK inhibitor-containing therapy (e.g. ibrutinib, acalabrutinib, zanubrutinib)
• Patients previously treated with bendamustine are eligible for the study treatment, in the case they had achieved objective response (CR or PR) and the last dose of bendamustine was administered ≥ 1 year before the estimated study treatment initiation date (C1D1)
• Tumor tissue at the lymphoma relapse after failure of BTK inhibitor. In case that a re-biopsy is not possible (e.g. urgent need to start study treatment), archival tissue blocks may be used to confirm the diagnosis
• Bone marrow examination by standard trephine biopsy including flow cytometry analysis within 8 weeks before study entry
• Age 18-80 years at the time of signing Informed Consent Form
• ECOG Performance Status of 0, 1, or 2
• Life expectancy ≥ 2 months
• Adequate hematologic function (unless due to underlying disease, as established for example, by extensive bone marrow involvement or due to hypersplenism secondary to the involvement of the spleen by MCL per the investigator), defined as follows:
• Hemoglobin ≥ 80g/L
• ANC ≥ 1,500/μL
• Platelet count ≥ 75,000/μL Enrollment of patients with lower counts is possible only after consulting the medical monitor.
• Adequate cardiac functions according to echocardiography (ECHO) within 6 months before study entry
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 12 months after the last dose of study treatment. Women must refrain from donating eggs during this same period. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
• Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

You may not qualify if:

• Prior organ transplantation
• Current Grade ≥ 2 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
• History of other malignancy that could affect compliance with the protocol or interpretation of results Patients with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study are eligible Patients with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for ≥ 2 years prior to enrollment are eligible Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage
• or 2) with no requirement for therapy at any time prior to study are eligible.
• Evidence of significant, uncontrolled, concomitant diseases that could affect compliance with the protocol or interpretation of results.
• Recent major surgery (e.g. within 4 weeks prior to the start of Cycle 1), other than for diagnosis
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or significant infections within 2 weeks before the start of Cycle 1.
• Clinically significant liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
• Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
• Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma):
• INR \> 1.5 x upper limit of normal (ULN) in the absence of therapeutic anticoagulation aPTT \> 1.5 x ULN in the absence of a lupus anticoagulant
• Serum AST and ALT \> 3 x ULN
• Total bilirubin \> 2 x ULN Patients with documented Gilbert disease may be enrolled if total bilirubin is \> 3.0 x ULN.
• Serum creatinine clearance \< 40 mL/min (using Cockcroft-Gault formula or creatinine levels assessed directly from the collected urine)
• Patients with suspected active or latent tuberculosis (as confirmed by a positive interferon-gamma release assay)

Sponsors & Collaborators

• Czech Lymphoma Study Group: lead

Study Sites (7)

University Hospital Brno

Brno, 625 00, Czechia

Location

University Hospital Hradec Králové

Hradec Králové, 500 05, Czechia

Location

University Hospital Olomouc

Olomouc, 775 20, Czechia

Location

University Hospital Ostrava

Ostrava, 70852, Czechia

Location

University Hospital Plzeň

Pilsen, 323 00, Czechia

Location

University Hospital Kralovske Vinohrady

Prague, 100 00, Czechia

Location

Charles University General Hospital

Prague, 12800, Czechia

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

polatuzumab vedotin; Bendamustine Hydrochloride; Rituximab

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

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pavel Klener, Prof.MD,PhD

  Czech Lymphoma Study Group

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pavel Klener, prof.MD,PhD

CONTACT

+420224962568; pavel.klener2@vfn.cz

Marketa Petrova, Ing.

CONTACT

+420224962676; petrova@lymphoma.cz

Study Design

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

Model Details: open-label, single arm, combination - polatuzumab vedotine + rituximab+bendamustin

Study Record Dates

• First Submitted: May 19, 2021
• First Posted: June 4, 2021
• Study Start: September 1, 2021
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2027
• Last Updated: June 4, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (7)