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ALX148, Rituximab and Lenalidomide for the Treatment of Indolent and Aggressive B-cell Non-Hodgkin Lymphoma | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE1/PHASE2

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

NCT05025800•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Phase I: histologically confirmed B-cell NHL, including marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, large B-cell lymphoma (including transformed MZL, transformed FL, Richter Syndrome with ALC \< 5,000 109/L, FL grade 3B, high grade B-cell lymphoma and primary mediastinal B-cell lymphoma), and composite lymphoma (concomitant indolent and aggressive B-NHL)
•Phase I: have failed at least one line of systemic therapy and not be eligible for known standard of care curative treatment option; patients with mantle cell lymphoma and aggressive B-cell lymphoma will need to have received 2 prior lines of systemic therapy.
•Phase II: histologically confirmed follicular lymphoma, grade 1, 2, or 3a or marginal zone lymphoma
•Phase II: have had no prior systemic treatment for lymphoma
•Phase II: high tumor burden disease, defined by meeting 1 or more of the following GELF criteria
•* Bulky disease defined as: a nodal or extranodal (except spleen) mass \>7cm in its greater diameter or, involvement of at least 3 nodal or extranodal sites (each with a diameter greater than \>3 cm)
•* Presence of at least one of the following B symptoms: fever (\>38C) of unclear etiology, night sweats, weight loss greater than 10% within the prior 6 months
•* Symptomatic splenomegaly
•* Impending organ compression or involvement
•* Any one of the following cytopenias due to lymphoma: hemoglobin \< 10 g/dL (6.25 mmol/L), platelets \< 100 x 10\^9/L , or absolute neutrophil count (ANC) \< 1.5 x 10\^9 /L
+39 more criteria

Exclusion Criteria

•Known active central nervous system lymphoma or leptomeningeal disease, except subjects with a history of central nervous system lymphoma treated and in remission \> 6 months
•Burkitt lymphoma
•Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) or lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia
•Any prior history of other malignancy besides B-NHL, unless the patient has been free of disease for \>= 3 years and felt to be at low risk for recurrence by the treating physician, except:
•* Adequately treated localized skin cancer without evidence of disease
•* Adequately treated cervical carcinoma in situ without evidence of disease
•Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of lenalidomide capsules, or put the study outcomes at undue risk
•Known history of human immunodeficiency virus (HIV), or active hepatitis C virus, or active hepatitis B virus infection, or any uncontrolled active significant infection, including suspected or confirmed JC virus infection and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)
•* Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated. Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded. Subjects with a history of hepatitis C who received antiviral treatment are eligible as long as PCR is negative
•History of immunodeficiency (with the exception of hypogammaglobulinemia) or concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc., or chronic administration glucocorticoid equivalent of \> 10 mg/day of prednisone) within 28 days of the first dose of study drug
+2 more criteria

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

October 13, 2021

Primary Completion Date

March 21, 2028

Completion Date

March 21, 2028

Last Updated

March 20, 2026

Enrollment

ESTIMATED participants

Conditions

Aggressive B-Cell Non-Hodgkin LymphomaAnn Arbor Stage III Grade 2 Follicular LymphomaAnn Arbor Stage III Grade 3 Follicular LymphomaAnn Arbor Stage III Marginal Zone LymphomaAnn Arbor Stage IV Grade 1 Follicular LymphomaAnn Arbor Stage IV Grade 2 Follicular LymphomaAnn Arbor Stage IV Grade 3 Follicular LymphomaAnn Arbor Stage IV Marginal Zone LymphomaComposite LymphomaIndolent B-Cell Non-Hodgkin LymphomaRefractory Aggressive B-Cell Non-Hodgkin LymphomaRefractory Follicular LymphomaRefractory Grade 3b Follicular LymphomaRefractory High Grade B-Cell LymphomaRefractory Mantle Cell LymphomaRefractory Marginal Zone LymphomaRefractory Primary Mediastinal (Thymic) Large B-Cell LymphomaRefractory Transformed Follicular Lymphoma to Diffuse Large B-Cell LymphomaRefractory Transformed Marginal Zone Lymphoma to Diffuse Large B-Cell LymphomaRichter Syndrome

Interventions

CD47 Antagonist ALX148

DRUG

Lenalidomide

DRUG

Rituximab

BIOLOGICAL

Rituximab, Lenalidomide, and Ibrutinib in Treating Patients With Previously Untreated Stage II-IV Follicular Lymphoma

NCT01829568

Ann Arbor Stage II Grade 1 Contiguous Follicular LymphomaAnn Arbor Stage II Grade 1 Non-Contiguous Follicular Lymphoma+10 more

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ACTIVE_NOT_RECRUITINGPHASE1/PHASE2

First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma

NCT03625037

DLBCLHigh-grade B-cell Lymphoma (HGBCL)+7 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 20, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

Rituximab, Lenalidomide, and Ibrutinib in Treating Patients With Previously Untreated Stage II-IV Follicular Lymphoma

First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma

Cardiovascular Events Among Adults Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma Treated With Standard of Care Chimeric Antigen Receptor T Cell Therapy

A Study on Fractionated Rituximab to Avoid Lysis Syndrome in Aggressive B-Lymphoma