The Efficacy and Safety of Pola-ZR2 Versus ZR2 in the Treatment of Old Patients With de Novo Diffuse Large B-cell Lymphoma

NCT ID: NCT06522555

Last Updated: 2024-08-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-29

Study Completion Date

2029-08-10

Brief Summary

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A multicenter, prospective, randomized, open-label, controlled trial to evaluate the efficacy and safety of Pola-ZR2 (polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide) versus ZR2 (zanubrutinib, rituximab and lenalidomide) in the treatment of old patients with de novo diffuse large B-cell lymphoma

Detailed Description

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This study will evaluate the efficacy and safety of Pola-ZR2 versus ZR2 in the treatment of elderly de novo diffuse large B-cell lymphoma patients. Subjects will be randomly assigned 1:1 to Pola-ZR2 or ZR2 regimen. The stratification will be performed according to international prognostic index (2-3 / 4-5).

Patients in Pola-ZR2 group will receive 6 cycles of polatuzumab vedotin 1.8 mg/kg, day 2 on the 1st cycle and day 1 on the 2nd to 6th cycle, zanubrutinib 160mg bid, day 1-21, orally, lenalidomide 25mg qd, day 2-11, orally, rituximab 375mg/m², day 1, intravenously, every 21 days. Patients in ZR2 group will receive 6 cycles of zanubrutinib 160mg bid, day 1-21, orally, lenalidomide 25mg qd, day 2-11, orally, rituximab 375mg/m², day 1, intravenously, every 21 days.

Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.

Conditions

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Diffuse Large B-Cell Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pola-ZR2

six courses of polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy

Group Type EXPERIMENTAL

polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide

Intervention Type DRUG

Drug: Polatuzumab vedotin, Zanubrutinib, Lenalidomide and Rituximab (Pola-ZR2)

Induction therapy:

The Pola-ZR2 regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles.

Dosage:

Polatuzumab vedotin 1.8 mg/kg, day 2 on the 1st cycle and day 1 on the 2nd to 6th cycle; Zanubrutinib, 160 mg bid, po, day 1-21; Lenalidomide, 25 mg qd, po, day 2-11; Rituximab, 375 mg/m2, ivgtt, day 1.

Maintenance therapy:

Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.

ZR2

six courses of zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy

Group Type ACTIVE_COMPARATOR

zanubrutinib, rituximab and lenalidomide

Intervention Type DRUG

Drug: Zanubrutinib, Lenalidomide and Rituximab (ZR2)

Induction therapy:

The ZR2 regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles.

Dosage:

Zanubrutinib, 160 mg bid, po, day 1-21; Lenalidomide, 25 mg qd, po, day 2-11; Rituximab, 375 mg/m2, ivgtt, day 1.

Maintenance therapy:

Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.

Interventions

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polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide

Drug: Polatuzumab vedotin, Zanubrutinib, Lenalidomide and Rituximab (Pola-ZR2)

Induction therapy:

The Pola-ZR2 regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles.

Dosage:

Polatuzumab vedotin 1.8 mg/kg, day 2 on the 1st cycle and day 1 on the 2nd to 6th cycle; Zanubrutinib, 160 mg bid, po, day 1-21; Lenalidomide, 25 mg qd, po, day 2-11; Rituximab, 375 mg/m2, ivgtt, day 1.

Maintenance therapy:

Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.

Intervention Type DRUG

zanubrutinib, rituximab and lenalidomide

Drug: Zanubrutinib, Lenalidomide and Rituximab (ZR2)

Induction therapy:

The ZR2 regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles.

Dosage:

Zanubrutinib, 160 mg bid, po, day 1-21; Lenalidomide, 25 mg qd, po, day 2-11; Rituximab, 375 mg/m2, ivgtt, day 1.

Maintenance therapy:

Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Patients must satisfy all of the following criteria to be enrolled in the study:

* Histologically-confirmed diffuse large B-cell lymphoma (without central nervous system involvement)
* Aged ≥ 80 years old or aged 70-79 with comprehensive geriatric assessment stratified as unfit or frail
* International prognostic index score 2 to 5
* At least 1 measurable site of disease (defined as lymph nodes with the long diameters longer than 1.5cm, or extra-nodal sites with the long diameters longer than 1.0cm; meanwhile, any lesion site with at least 2 measurable vertical diameters)
* Able to swallow capsules
* Life expectancy of at least 3 months determined by researchers
* The patient or his or her legal representative must provide written informed consent prior to any special examination or procedure for the research.
* Anti-lymphoma drugs have not been used before (except glucocorticoids)

Exclusion Criteria

Presence of any of the following criteria will exclude a patient from enrollment:

* Uncontrolled blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases
* Laboratory measures meet the following criteria at screening (unless caused by lymphoma):

Neutrophils\<1.5×10\^9/L Platelets\<80×10\^9/L ALT or AST is 2 times higher than the upper limits of normal (ULN), serum bilirubin are 1.5 times higher than the ULN.

Creatinine is 1.5 times higher than the ULN or eGFR is lower than 40ml/min/1.73m\^2 (according to Cockcroft-Gault Equation or MDRD Equation).

* uncontrollable or significant cardiovascular diseases, including but not limited to: Left ventricular ejection fraction\<50% Cardiomyopathy, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy QTc prolongation with clinical significance, QTc interval\>470ms (females) or 480ms (males), type 2 second-degree atrioventricular block or third-degree atrioventricular block
* Patients with HbsAg positive are required to have HBV DNA\<1.0×10\^3 IU/ml before entering the group. In addition, if the patient is HBsAg negative but HBcAb positive (regardless of HBsAb status), HBV DNA test is also required, and HBV DNA\<1.0×10\^3 IU/ml is required before entering the group
* Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol
* HIV-infected patients
* History of stroke or intracranial hemorrhage within 6 months prior to start of therapy
* Other medical conditions determined by the researchers that may affect the study
Minimum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ruijin Hospital

OTHER

Sponsor Role lead

Responsible Party

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Zhao Weili

Professor and Director, Shanghai Institute of Hematology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Shanghai Institute of Hematology, Rui-Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Weili Zhao

Role: CONTACT

+862164370045 ext. 610707

Li Wang

Role: CONTACT

+862164370045 ext. 610707

Facility Contacts

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Weili Zhao

Role: primary

+862164370045 ext. 610707

Pengpeng Xu

Role: backup

+862164370045 ext. 610707

Other Identifiers

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POTENT STUDY

Identifier Type: -

Identifier Source: org_study_id

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