NCT05025800

ALX148, Rituximab and Lenalidomide for the Treatment of Indolent and Aggressive B-cell Non-Hodgkin Lymphoma

A Phase I/II Open Label, Single Center, Study of the Combination of ALX148, Rituximab and Lenalidomide in Patients With Indolent and Aggressive B-Cell Non-Hodgkin Lymphoma

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 47 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial finds out the best dose, possible benefits and/or side effects of ALX148 in combination with rituximab and lenalidomide in treating patients with indolent and aggressive B-cell non-Hodgkin lymphoma. Immunotherapy with ALX148, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody that binds to a protein called CD20 found on B-cells, and may kill cancer cells. Giving ALX148 in combination with rituximab and lenalidomide may help to control the disease.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate safety and tolerability, and to determine the recommended phase II dose (RP2D) and schedule of CD47 antagonist ALX148 (ALX148) in combination with rituximab and lenalidomide in patients with relapsed or refractory B-non-Hodgkin lymphomas (NHLs) (both indolent and aggressive histology) in phase I. II. To evaluate the efficacy of the combination of ALX148, rituximab and lenalidomide at the RP2D (determined in phase I) in patients with previously untreated and high tumor burden indolent B-NHL in phase II. SECONDARY OBJECTIVE: I. To evaluate other toxicity and efficacy measures of the combination of ALX148, rituximab and lenalidomide. EXPLORATORY OBJECTIVE: I. To determine the pharmacodynamic effects and investigate biomarkers of response and resistance. OUTLINE: This is a phase I, dose-escalation study of ALX148 followed by a phase II study. Patients receive ALX148 intravenously (IV) over 1 hour once on days 1, 8, 15 and 22, or days 1 and 15, or day 1 depending on dose level. Patients also receive rituximab IV over 4-6 hours on days 1, 8, 15 and 22 of cycle 1, then on day 1 of cycles 2-6, and lenalidomide orally (PO) daily once (QD) on days 1-21 of cycles 1-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 7 and 30 days, then up to 3 years.

Conditions

• Aggressive B-Cell Non-Hodgkin Lymphoma
• Ann Arbor Stage III Grade 2 Follicular Lymphoma
• Ann Arbor Stage III Grade 3 Follicular Lymphoma
• Ann Arbor Stage III Marginal Zone Lymphoma
• Ann Arbor Stage IV Grade 1 Follicular Lymphoma
• Ann Arbor Stage IV Grade 2 Follicular Lymphoma
• Ann Arbor Stage IV Grade 3 Follicular Lymphoma
• Ann Arbor Stage IV Marginal Zone Lymphoma
• Composite Lymphoma
• Indolent B-Cell Non-Hodgkin Lymphoma
• Refractory Aggressive B-Cell Non-Hodgkin Lymphoma
• Refractory Follicular Lymphoma
• Refractory Grade 3b Follicular Lymphoma
• Refractory High Grade B-Cell Lymphoma
• Refractory Mantle Cell Lymphoma
• Refractory Marginal Zone Lymphoma
• Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma
• Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
• Refractory Transformed Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma
• Richter Syndrome

Interventions

Type	Name	Description
DRUG	CD47 Antagonist ALX148	Given IV
DRUG	Lenalidomide	Given PO
BIOLOGICAL	Rituximab	Given IV

Timeline

• Start date: 2021-10-13
• Primary completion: 2028-03-21
• Completion: 2028-03-21
• First posted: 2021-08-27
• Last updated: 2026-03-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study