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Aggressive B-Cell Non-Hodgkin LymphomaPhase 1/2NCT05025800

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

A Phase 1/2 study testing CD47 Antagonist ALX148, Lenalidomide and Rituximab in people with Aggressive B-Cell Non-Hodgkin Lymphoma and Ann Arbor Stage III Grade 2 Follicular Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CD47 Antagonist ALX148, Lenalidomide and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
1 siteUnited States
Study dates
13 Oct 2021to 21 Mar 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,000/mm^3, independent of growth factor support (within 28 days prior to signing informed consent)
  • Platelet counts >= 75,000/mm^3 or >= 50,000/mm^3 if bone marrow involvement with lymphoma, independent of transfusion support for >= 14 days in either situation (within 28 days prior to signing informed consent)
  • Hemoglobin > 8 g/dL, independent of transfusion support for >= 14 days (within 28 days prior to signing informed consent)
  • Serum aspartate transaminase (AST) and alanine transaminase (ALT) < 2 x upper limit of normal (ULN)
  • Creatinine clearance > 30 ml/min calculated by modified Cockcroft-Gault formula
  • Total bilirubin < 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3 g/dL
  • Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN
  • Must be able to adhere to the study visit schedule and other protocol requirements
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study (females of childbearing potential: must either completely abstain from heterosexual sexual conduct or must use 2 methods of reliable contraception, 1 highly effective [intrauterine device, birth control pills, hormonal patches, injections, vaginal rings, or implants] and at least 1 additional method [condom, diaphragm, cervical cap] of birth control). Reliable contraceptive methods must be started at least 4 weeks before lenalidomide, and continued for at least 4 weeks after last dose of lenalidomide. Males who are sexually active must be practicing complete abstinence or agree to a condom during sexual contact with a pregnant female or female of child bearing potential. Men must agree to not donate sperm during the study and 28 days after the last dose of lenalidomide. For females, these restrictions apply at least 4 weeks before study treatment, during the period of therapy and for 120 days after the last dose of study drug. For males, these restrictions apply during the period of therapy and for 28 days after the last dose of study drug
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study.
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program
  • Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
  • All study participants must be registered into the mandatory Revlimid REMS program, and be willing and able to comply with the requirements of the REMS program

Who cannot join

  • 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
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  • 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.
  • In regards to rituximab, exclusion is for known severe anaphylaxis to rituximab or any allergic reaction to rituximab that in the opinion of the PI and treating physician contraindicate re-challenge with 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
  • History of stroke or intracranial hemorrhage within 6 months prior to study entry
  • Vaccinated with live, attenuated vaccines within 4 weeks of study entry
  • Lactating or pregnant subjects
  • Administration of any investigational agent within 28 days of first dose of study drug
  • Patients who have undergone major surgery within 28 days or minor surgery within 3 days of first dose of study drug
  • Patients taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 10 mg/day prednisone (over these 4 weeks)
  • Life expectancy < 6 months
  • Neuropathy > grade 1
  • Prior exposure to lenalidomide or to a CD47/SIRP alpha antagonist/inhibitor, independently from indication
  • Patient who received chimeric antigen receptor (CAR) T-cell therapy within 1 month, autologous stem cell transplant within 3 months, allogeneic stem cell transplant within 6 months
  • Patients who have difficulty with or are unable to swallow oral medication, or have disease significantly affecting gastrointestinal function that would limit absorption of oral medication
  • Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)
  • History of hemolytic transfusion reaction secondary to allo-antibodies
  • Patients who have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. Agents with limited immunosuppressive activity (ex. Hydroxychloroquine) are allowed after discussion with the study PI ).
  • Patients who have a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Known history of symptomatic deep vein thrombosis or pulmonary embolism
  • Known history of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) or drug rash with eosinophilia and systemic symptoms (DRESS)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. To evaluate other toxicity and efficacy measures of the combination of ALX148, rituximab and lenalidomide.

EXPLORATORY OBJECTIVE:

  1. 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.

Being tested
CD47 Antagonist ALX148, Lenalidomide, Rituximab
Medical subject headings
Composite Lymphoma, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CD47 Antagonist ALX148Drug

    Also called ALX 148, ALX-148, ALX148, CD47/SIRPa-blocking Agent ALX148

    Given IV

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

Study groups in NCT05025800
Study groupRoleWhat they receive
Treatment (ALX148, rituximab, lenalidomide)ExperimentalPatients 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.
Receives: Drug: CD47 Antagonist ALX148; Drug: Lenalidomide; Biological: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to 28 days

  2. 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).

    Measured: At 6 months

Secondary outcomes (6)

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

    Will be assessed by the investigator based on Cheson, Lugano 2014. The number and percentage of subjects with an ORR will be tabulated. The best ORR will be recorded and summarized using exact method for 95% CI.

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

  2. Duration of response

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

    Measured: 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

  3. Progression-free survival (PFS)

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

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

  4. Overall survival (OS)

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

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

  5. Incidence of treatment-emergent adverse events (AEs)

    Safety summaries will include tabulations in the form of tables and listings. The frequency (number and percentage) of treatment-emergent AEs will be reported. Additional AE summaries will include AE frequency by AE severity and by relationship to study drug. Clinically significant abnormal laboratory values will be summarized.

    Measured: Up to 30 days

  6. Incidence of treatment-emergent AEs requiring temporary or permanent discontinuation of study drug or dose reductions

    Safety summaries will include tabulations in the form of tables and listings. The frequency (number and percentage) of treatment-emergent AEs will be reported. Additional AE summaries will include AE frequency by AE severity and by relationship to study drug. Clinically significant abnormal laboratory values will be summarized.

    Measured: Up to 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Aug 2021
  2. Study start13 Oct 2021
  3. Primary completion21 Mar 2028 (estimated)
  4. Study completion21 Mar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05025800
Sponsor's protocol ID
2021-0226
Other IDs
NCI-2021-08492, 2021-0226
Status last verified
Sep 2026
First submitted
5 Aug 2021
Last updated
18 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Duell J, Westin J. The future of immunotherapy for diffuse large B-cell lymphoma. Int J Cancer. 2025 Jan 15;156(2):251-261. doi: 10.1002/ijc.35156. Epub 2024 Sep 25.

    PubMed 39319495

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CD47 Antagonist ALX148, Lenalidomide and Rituximab in people with Aggressive B-Cell Non-Hodgkin Lymphoma and Ann Arbor Stage III Grade 2 Follicular Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended phase II dose (RP2D) and schedule of ALX148 (Phase I) (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05025800, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.

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