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

NCT05025800 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2021-0226NCI-2021-08492
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ann Arbor Stage III Grade 2 Follicular Lymphoma; Ann Arbor Stage III Grade 3 Follicular 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; Aggressive B-Cell Non-Hodgkin 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; Richter Syndrome

Outcome Measures

Primary Outcomes (2)

• Recommended phase II dose (RP2D) and schedule of ALX148 (Phase I)

  Up to 28 days

• Complete remission (CR) rate (Phase II)

  Response will be assessed by the investigator based on the 2014 Cheson Lugano criteria. The number and percentage of subjects with a CR at the end of treatment will be tabulated. The CR rate will be estimated with its exact 95% confidence interval (CI).

  At 6 months

Secondary Outcomes (6)

• Overall response rate (ORR) (CR + partial response [PR])

  After 6 cycles of treatment (At the end of Cycle 1 (each cycle is 28 days)

• Duration of response

  From the time by which measurement criteria for CR or PR, whichever is recorded first, is met until death or the first date by which progressive disease is documented, assessed up to 3 years

• Progression-free survival (PFS)

  From the date of cycle 1, day 1 (At the end of Cycle 1 (each cycle is 28 days)

• Overall survival (OS)

  From the date of cycle 1, day 1 (At the end of Cycle 1 (each cycle is 28 days)

• Incidence of treatment-emergent adverse events (AEs)

  Up to 30 days

Study Arms (1)

Treatment (ALX148, rituximab, lenalidomide)

EXPERIMENTAL

Patients receive ALX148 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 PO QD on days 1-21 of cycles 1-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: CD47 Antagonist ALX148; Drug: Lenalidomide; Biological: Rituximab

Interventions

CD47 Antagonist ALX148 DRUG

Given IV

Also known as: ALX 148, ALX-148, ALX148, CD47/SIRPa-blocking Agent ALX148, SIRPa Variant ALX148

Treatment (ALX148, rituximab, lenalidomide)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima

Treatment (ALX148, rituximab, lenalidomide)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (ALX148, rituximab, lenalidomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Pleural or peritoneal serous effusion (irrespective of cell content)
• Lactate dehydrogenase \[LDH\] \> upper limit of normal (ULN) or beta 2 microglobulin \> ULN
• Phase II: stage III or IV disease
• Bi-dimensionally measurable disease, with at least one nodal lesion \>= 1.5 cm or one extra-nodal lesion \>= 1 cm in longest diameter by computed tomography (CT), positron emission tomography (PET)/CT, and/or magnetic resonance imaging (MRI)
• Must be \>= 18 years of age

You may not qualify if:

• 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
• Known anaphylaxis or immunoglobulin (Ig)E-mediated hypersensitivity to murine proteins or to any component of ALX148, lenalidomide and/or rituximab.
• Requires chronic treatment with strong CYP3A inhibitors, for a list of strong CYP3A inhibitors. If patients have been on a strong CYP3A inhibitor in the past, they will not be eligible if the CYP3A inhibitor was administered within 7 days of the first dose of study drug
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study
• Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block
• Active bleeding or known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Composite Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone

Interventions

ALX148; Lenalidomide; Rituximab; CT-P10

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Complex and Mixed; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Paolo Strati, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: August 27, 2021
• Study Start: October 13, 2021
• Primary Completion (Estimated): March 21, 2028
• Study Completion (Estimated): March 21, 2028
• Last Updated: March 20, 2026

Record last verified: 2026-03

Locations

US (1)