Pomalidomide Plus Anti-CD20 Antibody and Prednisone in Frontline Indolent B-Cell Lymphoma

Official title

Pomalidomide Plus Anti-CD20 Antibody and Prednisone in Frontline Indolent B-Cell Lymphoma: A Prospective, Multicenter, Phase II Study

Overview

A Phase II Study of Pomalidomide Combined with Anti-CD20 Monoclonal Antibody and Prednisone in Frontline Indolent B-Cell Lymphoma Objective: This prospective, single-arm, Phase II trial aims to evaluate the efficacy and safety of first-line pomalidomide plus anti-CD20 antibody and prednisone in patients with indolent B-cell lymphoma. Study Population: Approximately 30 adult patients (age ≥18 years) will be enrolled. Eligible histologies include follicular lymphoma (FL), CD20-positive marginal zone lymphoma (MZL: extranodal MALT, splenic SMZL, nodal NMZL), indolent mantle cell lymphoma (MCL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Patients must be treatment-naïve, have an indication for systemic therapy, ECOG performance status 0-2, and adequate bone marrow reserve (ANC ≥1.5×10⁹/L, platelets ≥75×10⁹/L, hemoglobin ≥9.0 g/dL; lower thresholds permitted if marrow/spleen involvement, per investigator discretion). Adequate organ function is required: bilirubin ≤2×ULN, ALT/AST ≤2.5×ULN, and creatinine clearance \>30 mL/min. Life expectancy must be ≥3 months, and written informed consent is mandatory. Exclusion Criteria: Patients are excluded if they have another malignancy within 5 years (unless curatively treated without recurrence), CNS lymphoma involvement, transformation to high-grade lymphoma, uncontrolled infection, severe comorbidities affecting study participation, significant non-lymphoma-related organ dysfunction (ALT/AST \>3×ULN, bilirubin \>2×ULN, creatinine \>1.5×ULN), active CNS dysfunction, major surgery within 30 days, pregnancy or lactation, lack of contraception in women of childbearing potential, known drug hypersensitivity, or any condition deemed unsuitable by the investigator. Treatment Regimen: Induction consists of six 28-day cycles. Anti-CD20 antibody is administered at 375 mg/m² weekly during Cycle 1 and on Day 1 of Cycles 2-6. Pomalidomide is given at 4 mg/day on Days 2-22 of Cycles 1-6. Prednisone is administered at 100 mg/day on Days 1-5 of Cycles 1-6. Maintenance therapy continues for 2 years with pomalidomide 4 mg/day on Days 1-14 and anti-CD20 antibody 375 mg/m² on Day 1 every 8 weeks. Endpoints: The primary endpoint is overall response rate (ORR). Secondary endpoints include complete response rate (CR), progression-free survival (PFS), overall survival (OS), and safety (hematologic and non-hematologic adverse events). Statistical Methods: Continuous variables will be summarized with descriptive statistics; categorical variables with frequencies and percentages. Time-to-event endpoints (PFS, OS, and duration of response) will be analyzed using the Kaplan-Meier method, reporting medians, quartiles, and 90% confidence intervals, along with event and censoring counts. ORR will be tested statistically and reported with a 90% confidence interval. Timeline: The study is expected to begin in January 2026, complete enrollment by December 2026, and conclude by December 2027. The total planned sample size is 30 patients.

Interventions

• Drug Pomalidomide
  Pomalidomide is given at 4 mg/day on Days 2-22 of Cycles 1-6. Anti-CD20 antibody is administered at 375 mg/m² weekly during Cycle 1 and on Day 1 of Cycles 2-6. Prednisone is administered at 100 mg/day on Days 1-5 of Cycles 1-6.

Primary outcome measures

• overall response rate [Time frame: At the end of Cycle 6 (each cycle is 28 days)]

Secondary outcome measures (3)

• complete response rate [Time frame: At the end of Cycle 6 (each cycle is 28 days)]
• progression-free survival [Time frame: one-year]
• overall survival [Time frame: one-year]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years, regardless of sex;
• Confirmed diagnosis of follicular lymphoma (FL), or histopathologically confirmed CD20-positive marginal zone lymphoma (MZL), including extranodal marginal zone lymphoma (MALT), splenic marginal zone lymphoma (SMZL), and nodal marginal zone lymphoma (NMZL),or confirmed diagnosis of indolent mantle cell lymphoma (MCL);
• Patients with a confirmed diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL);
• Confirmed diagnosis of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia;
• Presence of indications for treatment of indolent B-cell lymphoma;
• No prior systemic antitumor therapy for lymphoma;
• ECOG-PS score 0-2;
• Essentially normal bone marrow hematopoietic function, with routine blood tests as follows: white blood cell count >3000/uL, absolute neutrophil count ≥1.5 × 10\^9/L (use of granulocyte colony-stimulating factor is allowed), platelet count ≥75 × 10\^9/L (transfusion to reach this minimum platelet count is allowed), and hemoglobin ≥9.0 g/dL (prior red blood cell transfusion or use of recombinant human erythropoietin is allowed). If peripheral blood abnormalities are caused by lymphoma involvement of the bone marrow or spleen, neutrophils≥1.0 × 10\^9/L and platelets≥50 × 10\^9/L are acceptable (the investigator may determine at his/her discretion whether enrollment is appropriate);
• Normal function of major organs:

• Hepatic function: serum bilirubin ≤2.0 × ULN; serum ALT and AST ≤2.5 × ULN;
• Renal function: creatinine clearance >30 mL/min;
• Expected survival≥3 months as judged by the investigator; Voluntary written informed consent signed before trial screening;

Exclusion criteria

• Current or prior other malignancy, unless curative treatment has been performed and there has been no evidence of recurrence or metastasis within the past 5 years;
• Lymphoma involvement of the central nervous system or transformation to a higher-grade lymphoma;
• Hepatic or renal dysfunction unrelated to lymphoma: alanine aminotransferase (ALT) >3 times the upper limit of normal, aspartate aminotransferase (AST) >3 times the upper limit of normal, total bilirubin (TBIL) >2 times the upper limit of normal, or serum creatinine >1.5 times the upper limit of normal;
• Other serious medical conditions that would affect this study (e.g., uncontrolled diabetes, gastric ulcer, or other serious cardiopulmonary diseases). The investigator has the authority to make this determination;
• Severe or uncontrolled infection;
• Clinically manifest central nervous system dysfunction;
• Major surgery within the past 30 days (excluding lymph node biopsy);
• Pregnant or lactating women, or women of childbearing potential who have not used contraceptive measures;
• Allergy to the study drug; Patients considered unsuitable for enrollment by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• The First Affiliated Hospital of Soochow University — Suzhou

Publications

• Kiesewetter B, Willenbacher E, Willenbacher W, Egle A, Neumeister P, Voskova D, Mayerhoefer ME, Simonitsch-Klupp I, Melchardt T, Greil R, Raderer M; AGMT Investigators. A phase 2 study of rituximab plus lenalidomide for mucosa-associated lymphoid tissue lymphoma. Blood. 2017 Jan 19;129(3):383-385. doi: 10.1182/blood-2016-06-720599. Epub 2016 Nov 22. No abstract available. PMID 27879257
• Cohen JB, Switchenko JM, Koff JL, Sinha R, Kaufman JL, Khoury HJ, Bumpers N, Colbert A, Hutchison-Rzepka A, Nastoupil LJ, Heffner LT, Langston AA, Lechowicz MJ, Lonial S, Flowers CR. A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma. Br J Haematol. 2015 Nov;171(4):539-4 PMID 26248505
• Martin P, Jung SH, Pitcher B, Bartlett NL, Blum KA, Shea T, Hsi ED, Ruan J, Smith SE, Leonard JP, Cheson BD. A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). Ann Oncol. 2017 Nov 1;28(11):2806-2812. doi: 10.1093/annonc/mdx496. PMID 28945884
• Huntington SF, Schuster SJ, Ding W, Koehler AB, Brander DM, Rosenthal AC, Leis JF, Tun HW, Moustafa MA, Iqbal M, He W, Kearney AS, McKinlay TP, Gui M, Mato AR. DTRMWXHS-12, a novel Bruton tyrosine kinase inhibitor, in combination with everolimus and pomalidomide in patients with relapsed/refractory lymphomas: An open-label, multicenter, phase 1a/1b study. Am J Hematol. 2023 May;98(5):739-749. doi: PMID 36810799
• Walewski J, Paszkiewicz-Kozik E, Michalski W, Rymkiewicz G, Szpila T, Butrym A, Giza A, Zaucha JM, Kalinka-Warzocha E, Wieczorkiewicz A, Zimowska-Curylo D, Knopinska-Posluszny W, Tyczynska A, Romejko-Jarosinska J, Dabrowska-Iwanicka A, Gruszecka B, Jamrozek-Jedlinska M, Borawska A, Holda W, Porowska A, Romanowicz A, Hellmann A, Stella-Holowiecka B, Deptala A, Jurczak W. First-line R-CVP versus R-C PMID 31792945
• Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-Line Treatment of Patients With Indolent Non-Hodgkin Lymphoma or Mantle-Cell Lymphoma With Bendamustine Plus Rituximab Versus R-CHOP or R-CVP: Results of the BRIGHT 5-Year Follow-Up Study. J Clin Oncol. 2019 Apr 20;37(12):984-991. doi: 10.1200/JCO. PMID 30811293
• Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, Lopez-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, Andre M, Zachee P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Sall PMID 30184451
• Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15 PMID 25439689

Identifiers

NCT: NCT07609446 · （2026）No. 154

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗