Veltuzumab and Milatuzumab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Beth Christian

Status and phase: Completed; Phase 2; Phase 1

Conditions: Lymphoma

Treatments: Biological: veltuzumab and milatuzumab; Procedure: Quantitative T-, B-, and NK cell subsets; Biological: veltuzumab; Procedure: Pharmacokinetics; Procedure: Human Anti-Human Antibodies; Biological: milatuzumab; Procedure: Correlative/Special Studies

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00989586

OSU-09024

NCI-2011-03150 (Registry Identifier)

Details and patient eligibility

About

A phase I dose escalation study of veltuzumab and milatuzumab in relapsed and refractory B-cell NHL. The phase I study will be followed by a pilot phase II study.

Full description

A phase I/II study of veltuzumab combined with milatuzumab in relapsed and refractory non-Hodgkin's lymphoma. Both agents are well-tolerated in early phase clinical testing with infusion reactions as the primary observed toxicity. Preclinical testing in vitro and in vivo have demonstrated single agent activity for both veltuzumab and milatuzumab. In mantle cell lymphoma cell lines and SCID mouse models, synergist effects were observed when milatuzumab was combined with rituximab. Veltuzumab has several advantages over rituximab including slower off-rates, shorter infusion times, higher potency, and improved therapeutic responses in animal models. Previous and ongoing clinical investigations support the concept of combining monoclonal antibodies in NHL.

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 prior therapy

• Patients with rituximab-refractory disease (defined as having less than a partial response to the prior rituximab-containing regimen) or rituximab-sensitive disease (defined as having a complete response or partial response to the last rituximab-containing regimen [provided it has been ≥ 3 months since the last dose of rituximab]) are eligible.

• Age >18 years.

• Eastern Cooperative Oncology Group (ECOG)performance status 0-2.

• Patients must have normal organ and marrow function as defined below:

  • Absolute neutrophil count ≥ 1000/μL
  • Platelets ≥ 75,000/μL
  • Total bilirubin ≤ 2.0 X institutional upper limit of normal
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
  • Creatinine ≤ 2.0 mg/dL

• Patients who have relapsed after stem cell transplant are eligible for this trial.

• Patients with active Hepatitis B infection are not eligible.

• Non-pregnant and non-nursing. Women of child bearing potential and men must agree to use contraception prior to study entry and for duration of study participation.

• Must possess the ability to understand and the willingness to sign a written informed consent document.

Phase II

-Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension >10 mm or in the case of Waldenstrom's macroglobulinemia, the presence of an IgM paraprotein level 2x the upper limit of normal.

Exclusion criteria

• Must be recovered from all toxicities from prior therapy or radiation (excluding alopecia).
• No known CNS lymphoma.
• History of documented human anti-globulin antibodies.
• No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations.
• HIV-positive patients.
• Pregnant women.
• Patients with secondary malignancies with exception of non-melanomatous skin cancers.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 2 patient groups

Phase I

Experimental group

Description:

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.

Treatment:

Procedure: Correlative/Special Studies

Biological: milatuzumab

Procedure: Human Anti-Human Antibodies

Procedure: Pharmacokinetics

Procedure: Quantitative T-, B-, and NK cell subsets

Biological: veltuzumab

Procedure: Pharmacokinetics

Phase II

Experimental group

Description:

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.

Treatment:

Biological: veltuzumab and milatuzumab