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

Lymphoma Clinical Trial

Official title:

A Phase I/II Study of Veltuzumab (IMMU-106, hA20), a Humanized Anti-CD20 Monoclonal Antibody, Combined With Milatuzumab (IMMU-115, hLL1), a Humanized Anti-CD74 Monoclonal Antibody, in Relapsed and Refractory B-cell Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00989586
• Other study ID #: OSU-09024
• Secondary ID: NCI-2011-03150
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 2, 2009
• Last updated: September 2, 2015
• Start date: September 2009
• Est. completion date: September 2015

Study information

• Verified date: September 2015
• Source: Ohio State University Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: September 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• milatuzumab
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
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.

Procedure:
• Correlative/Special Studies
To correlate Fc? 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
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
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).
• Pharmacokinetics
To assess the pharmacokinetics of milatuzumab 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 2 of week 1 and day 1 of weeks 2, 4, 12 and 36. Additional samples will be collected days 3 through 6 of week 1.
• Human Anti-Human Antibodies
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.

Biological:
• veltuzumab and milatuzumab
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.

Locations

Country	Name	City	State
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Beth Christian	Immunomedics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine dose limiting toxicity (DLT)and maximum tolerated dose (MTD)for phase I and overall response rate for phase II along with defining toxicities for the combination.		up to 2 years	Yes
Secondary	Progression-free survival (PFS)		up to 2 years	No
Secondary	Fc?-receptor polymorphism response to treatment		up to 2 years	No
Secondary	Quantitative T-, B-, and NK-cell subsets using flow cytometry		up to 1 year	No
Secondary	Access pharmacokinetics		up to 2 years	No
Secondary	Monitor human anti-veltuzumab antibodies and human anti-milatuzumab (HAHA)		up to 2 years	No

External Links

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