A Study Comparing Rituximab/Bendamustin(RB) Alternating With Rituximab/Bendamustin/Cytarabin(RBAC) With RB Therapy in Elderly Patients With Mentle Cell Lymphoma

Sponsor

Kim, Seok Jin (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05245656

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 2, multicenter, open-label, active-controlled randomized trial to determine efficacy and safety of rituximab/bendamustine (RB) alternating with rituximab/bendamustine/cytarabine (RBAC) compared with standard RB alone in the first-line treatment of elderly patients with mantle cell lymphoma, who are not eligible for high-dose therapy followed by autologous stem cell transplantation.

Condition or Disease	Intervention/Treatment	Phase
Mantle Cell Lymphoma	Drug: RB/RBAC alternating Drug: RB	Phase 2

Detailed Description

Eligible patients will be randomly assigned to either the investigational treatment arm (RB alternating with RBAC) or the standard treatment arm (RB) in a 1:1 ratio. Patients will be stratified by age (≥70 years vs. 60-69), histologic morphology (blastoid/pleomorphic vs. non-blastoid/non-pleomorphic), and MIPI-C risk score (0/1 vs. 2/3).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Trial Comparing Rituximab/Bendamustine(RB) Alternating With Rituximab/Bendamustine/Cytarabine(RBAC) With RB as Induction Therapy in Elderly Patients With Newly Diagnosed and Transplant-ineligible Mantle Cell Lymphoma

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Dec 31, 2029

Anticipated Study Completion Date :

Dec 31, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RB/RBAC alternating Every 4 weeks for 6 cycles RB (1st, 3rd, and 5th cycles) Rituximab + Bendamustine RBAC (2nd, 4th, and 6th cycles) Rituximab + Bendamustine + Cytarabine	Drug: RB/RBAC alternating Patients assigned to the RB alternating with RBAC arm will receive six cycles of alternating RB (odd cycles) or RBAC (even cycles) RB (1st, 3rd, and 5th cycles) Rituximab 375mg/m2, IV, D1 Bendamustine 90mg/m2, IV, D1-2 RBAC (2nd, 4th, and 6th cycles) Rituximab 375mg/m2, IV, D1 Bendamustine 70mg/m2, IV, D2-3 Cytarabine 500mg/m2, IV, D2-4
Active Comparator: RB Every 4 weeks for 6 cycles - Rituximab + Bendamustine	Drug: RB Every 4 weeks for 6 cycles Rituximab 375mg/m2, IV, D1 Bendamustine 90mg/m2, IV, D1-2

Arm

Intervention/Treatment

Experimental: RB/RBAC alternating

Every 4 weeks for 6 cycles RB (1st, 3rd, and 5th cycles) Rituximab + Bendamustine RBAC (2nd, 4th, and 6th cycles) Rituximab + Bendamustine + Cytarabine

Drug: RB/RBAC alternating

Patients assigned to the RB alternating with RBAC arm will receive six cycles of alternating RB (odd cycles) or RBAC (even cycles) RB (1st, 3rd, and 5th cycles) Rituximab 375mg/m2, IV, D1 Bendamustine 90mg/m2, IV, D1-2 RBAC (2nd, 4th, and 6th cycles) Rituximab 375mg/m2, IV, D1 Bendamustine 70mg/m2, IV, D2-3 Cytarabine 500mg/m2, IV, D2-4

Active Comparator: RB

Every 4 weeks for 6 cycles - Rituximab + Bendamustine

Drug: RB

Every 4 weeks for 6 cycles Rituximab 375mg/m2, IV, D1 Bendamustine 90mg/m2, IV, D1-2

Outcome Measures

Primary Outcome Measures

Progression-freesurvival [Up to 84 months]

Secondary Outcome Measures

Overall Survival [Up to 84 months]
Duration of Response [Up to 84 months]
Event Free Survival [Up to 84 months]
Overall response rate [Up to 84 months]
Adverse events [From the day 1 of the clinical trial to 28 days after last drug administration]

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

newly diagnosed, previously untreated, histologically confirmed CD20+ mantle cell lymphoma, confirmed by WHO classification criteria
age ≥70 years or 60-69 years if the patients are ineligible for high-dose therapy with autologous stem cell transplantation.
ECOG performance status 2 or less
Adequate organ functions

adequate heart function: LVEF ≥50% by echocardiography or MUGA
adequate renal function: serum creatinine ≤ 2.0mg/dL or CrCl ≥40 mL/min based on the Cockcroft-Gault method
adequate hepatic function: ≤2.5 times the upper limit of ALT (≤5 times the upper limit of ALT if the elevation is attributed by underlying lymphoma) and ≤2 times the upper limit of ALT (≤3 times the upper limit of total bilirubin if the elevation is attributed by underlying lymphoma)
adequate hematologic function: absolute neutrophil counts (ANC) ≥ 1,500/mL, platelet counts ≥ 100,000/mL (any ANC and platelet counts are allowed, if they were related to bone marrow involvement)

Written informed consent

Exclusion Criteria:

In-situ mantle cell lymphoma
Ann Arbor stage 1 disease
Prior treatment for Hodgkin lymphoma or non-Hodgkin lymphoma within the last 5 years.
Active malignancy within the past 3 years except for localized non-melanoma skin cancer, papillary thyroid cancer, cervical carcinoma in situ, breast cancer in situ, or localized prostate cancer that has been definitely treated,
Central nervous system involvement
HBsAg (+) or anti-HBc Ab (+) (patients will be eligible if they receive appropriate prophylactic antiviral therapy using entecavir, tenofovir, and so on)
History of prior hepatitis C infection (patients positive for HCV IgG will be eligible if they are negative for HCV-RNA)
Known history of human immunodeficiency virus (HIV) infection
any serious illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study

Congestive heart failure ≥ NYHA class 3
Acute coronary syndrome within 6 months (unstable angina or new-onset angina, myocardial infarct, or ventricular arrhythmia)
History of significant neurological or psychological disorder including dementia and seizure disorder
Severe chronic obstructive pulmonary disease with hypoxemia
Cerebrovascular disease including transient ischemic attack within the past 6 months
Non-healing wound, ulcer, or bone fracture
Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy

concomitant administration of any other experimental drugs under investigation
Known hypersensitivity to bendamustine, rituximab, cytarabine, or mannitol
major surgical procedure or significant trauma within 28 days before start of study treatment, open biopsy within 7 days before start of study treatment
If the patient's partner is a woman who could possibly get pregnant, men who didn't have a vasectomy must agree to use medically recommended methods for adequate contraception (tubal ligation, intrauterine devices, or barriers [diaphragm, cervical cap] in the patient's partner and the use of condoms in men) when sexually active.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Samsung Medical Center	Seoul	Gangnam-Gu	Korea, Republic of	06351

Sponsors and Collaborators

Kim, Seok Jin

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Kim, Seok Jin, Principal Investigator, Samsung Medical Center

ClinicalTrials.gov Identifier:

NCT05245656

Other Study ID Numbers:

2021-11-126

First Posted:

Feb 18, 2022

Last Update Posted:

Apr 25, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Lymphoma

Lymphoma, Mantle-Cell

Study Results

No Results Posted as of Apr 25, 2022