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Also known as monoclonal antibody, IMMU-115, hLL1, CD74, humanized CD74
milatuzumab · 4 trials · 10 indications
Dose-limiting toxicity was assessed during induction therapy for phase I.
Patients received a fixed dose of Veltuzumab IV 200 mg/m2 and Milatuzumab was dose escalated
Per International Response Criteria (Cheson JCO 2007) for target lesions and assessed by CT, MRI or PET: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses; Overall Response (OR) = CR + PR.
Will be assessed using laboratory and clinical data comparing baseline lab results and clinical condition to the lab results and clinical condition/adverse events during treatment and follow-up timepoints up to 2 years.
Will be assessed using the BILAG scoring model for lupus disease activity and symptoms by comparing baseline BILAG measurements against the BILAG measurements obtained during treatment and during follow-up for up to 2 years.
| Arm | Type | Description |
|---|---|---|
| Phase I | EXPERIMENTAL | Phase I portion of the study, a standard 3+3 dose escalation schema will be followed. Patients will receive veltuzumab IV weekly on day 1 for 4 doses and milatuzumab weekly on for 4 total doses during induction therapy. Induction therapy will be defined as the first 4 weeks of study therapy. During week 1 of induction therapy, patients will receive veltuzumab alone on day 1 and milatuzumab alone on day 2 to prevent overlapping infusion reactions. Starting week 2, veltuzumab will be given on day 1 and milatuzumab will be given on day 4. |
| Phase II | EXPERIMENTAL | Patients will receive veltuzumab IV weekly for 4 doses and milatuzumab IV weekly on day 2 of week 1 and on day 4 of weeks 2-4 for 4 total doses during induction therapy. Patients may continue on therapy to receive extended induction therapy provided they do not experience significant toxicity or rapid disease progression during the initial 4 week induction. |
| milatuzumab | EXPERIMENTAL | different doses of hLL1 |
| Multiple Doses | OTHER | Multiple Dose levels |
| Milatuzumab SC 250 mg | EXPERIMENTAL | Milatuzumab 250 mg will be administered subcutaneously once weekly for 4 weeks. |
| Milatuzumab 150 mg SC | EXPERIMENTAL | Milatuzumab 150 mg will be administered subcutaneously once weekly for 4 weeks. |
| Placebo SC | PLACEBO_COMPARATOR | Placebo will be administered subcutaneously once weekly for 4 weeks. |
| Name | Type | Description |
|---|---|---|
| milatuzumab | BIOLOGICAL | Patient will receive milatuzumab weekly for 4 total doses during induction therapy. Induction therapy will be defined as the first 4 weeks of study therapy. During week 1 of induction therapy, patients will receive milatuzumab on day 2. Starting in week 2, milatuzumab will be given on day 4. Provided the patient does not experience excessive toxicity or disease progression during induction therapy, the patient may continue treatment with extended induction therapy, consisting of veltuzumab day 1 and milatuzumab day 4 of weeks 12, 20, 28, and 36. |
| veltuzumab | BIOLOGICAL | Patient will receive veltuzumab weekly for 4 total doses during induction therapy. Induction therapy will be defined as the first 4 weeks of study therapy. Provided the patient does not experience excessive toxicity or disease progression during induction therapy, the patient may continue treatment with extended induction therapy, consisting of veltuzumab day 1 and milatuzumab day 4 of weeks 12, 20, 28, and 36. |
| Correlative/Special Studies | PROCEDURE | To correlate Fcγ receptor polymorphisms with response to treatment with the combination of veltuzumab and milatuzumab. Whole blood will be collected pre-treatment on day 1. |
| Quantitative T-, B-, and NK cell subsets | PROCEDURE | Quantitative T-, B-, and NK- cell subsets will be assessed using flow cytometry to quantify the percentage and absolute number of cells expressing CD4, CD8, CD56, CD16, CD19, and CD20 pre-treatment on day 1, after induction (week 5, day 1), and prior to the start of therapy on day 1 week 12, day 1 week 36, and then every 4 months for one year. |
| Pharmacokinetics | PROCEDURE | To assess the pharmacokinetics of veltuzumab in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Pharmacokinetics will be assessed with blood samples collected at the following time points: immediately pre- and post-infusion on day 1 of weeks 1, 2, 4, 12 and 36. One additional sample will be collected each of weeks 5 through 10 (sample may be collected any day during each of these weeks). |
| Human Anti-Human Antibodies | PROCEDURE | To monitor for the development of human anti-veltuzumab antibodies and human anti-milatuzumab antibodies (HAHA) in patients receiving treatment with veltuzumab and milatuzumab. Patients will be monitored for the development of HAHA at the following timepoints: pre-treatment on day 1 of week 1, pre-treatment on day 1 of week 4, pre-treatment on day 1 of week 12, and pre-treatment on day 1 of week 36. |
| veltuzumab and milatuzumab | BIOLOGICAL | Patient will receive veltuzumab and milatuzumab weekly for 4 total doses during induction therapy. Induction therapy will be defined as the first 4 weeks of study therapy. During week 1 of induction therapy, patients will receive veltuzumab on day 1 and milatuzumab on day 2. Starting in week 2, veltuxumab will be given on day 1 and milatuzumab will be given on day 4. Provided the patient does not experience excessive toxicity or disease progression during induction therapy, the patient may continue treatment with extended induction therapy, consisting of veltuzumab day 1 and milatuzumab day 4 of weeks 12, 20, 28, and 36. |
| Placebo | DRUG | Placebo will be administered subcutaneously once weekly for 4 weeks. |
Inclusion Criteria: * Histologically confirmed B-cell non-Hodgkin lymphoma (NHL), including any of the following: * Marginal zone lymphoma * Waldenstrom macroglobulinemia (lymphoplasmacytic lymphoma) * Follicular lymphoma * Mantle cell lymphoma * Relapsed or refractory disease after ≥ 1 pr...
Milatuzumab is an investigational monoclonal antibody studied in hematologic cancers and autoimmune conditions. Research indications include chronic lymphocytic lymphoma, multiple myeloma, B-cell non-Hodgkin lymphoma, and cutaneous lupus erythematosus. It remains in clinical development and is not an approved therapy for any of these conditions.
Milatuzumab targets CD74, a cell surface receptor. It is classified as an antagonist antibody directed against that target. By binding CD74, the antibody is designed to interfere with CD74-mediated signaling in cells that express the receptor, which include certain B-cell malignancies and immune cell populations.
Milatuzumab is being developed by Gilead Sciences, Inc., which trades on the Nasdaq under the ticker GILD. The company holds the asset as part of its oncology and immunology pipeline, and the compound is identified in public chemical databases under the ChEMBL identifier CHEMBL1743040.
Milatuzumab is in Phase 1 clinical development. It is an investigational agent and has not been approved by the FDA for any indication. Reported studies were early-stage Phase 1 or Phase 1/2 trials, and no active trials are currently listed for the program.
Completed studies include NCT01845740, a Phase 1b trial of subcutaneous milatuzumab in systemic and cutaneous lupus erythematosus with 22 participants, and NCT00989586, which tested veltuzumab and milatuzumab in relapsed or refractory B-cell non-Hodgkin lymphoma with 35 participants. NCT00603668 studied milatuzumab in chronic lymphocytic leukemia, and NCT00421525 studied it in multiple myeloma.
Yes. Milatuzumab is also known as hLL1, and the two names refer to the same monoclonal antibody. Early trial records, including the Phase 1/2 studies in chronic lymphocytic leukemia and multiple myeloma, list the agent as hLL1, while later records and the lupus study use the name milatuzumab.