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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Immunomedics, Inc.
Information provided by (Responsible Party):
Beth Christian, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00989586
First received: October 2, 2009
Last updated: September 28, 2014
Last verified: September 2014

October 2, 2009
September 28, 2014
September 2009
December 2014   (final data collection date for primary outcome measure)
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. [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
  • Overall objective response rate (Phase II) [ Designated as safety issue: No ]
  • Adverse events as assessed by NCI CTCAE v3.0 (Phase I) [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00989586 on ClinicalTrials.gov Archive Site
  • Progression-free survival (PFS) [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
  • Fcγ-receptor polymorphism response to treatment [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
  • Quantitative T-, B-, and NK-cell subsets using flow cytometry [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
  • Access pharmacokinetics [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
  • Monitor human anti-veltuzumab antibodies and human anti-milatuzumab (HAHA) [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Safety and toxicity profile as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Fcγ-receptor polymorphism analysis [ Designated as safety issue: No ]
  • Quantitative T-, B-, and NK-cell subsets [ Designated as safety issue: No ]
  • Pharmacokinetics [ Designated as safety issue: No ]
  • Human anti-human antibodies [ Designated as safety issue: No ]
  • Pharmacodynamics [ Designated as safety issue: No ]
  • CD74 expression [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Veltuzumab and Milatuzumab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
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

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • 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.
    Other Name: monoclonal antibody
  • Biological: 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.
    Other Name: monoclonal antibody
  • Procedure: Correlative/Special Studies
    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.
    Other Name: blood samples
  • Procedure: 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.
    Other Name: blood samples
  • Procedure: 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).
    Other Name: blood samples
  • Procedure: 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.
    Other Name: blood samples
  • Procedure: 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.
    Other Name: blood samples
  • 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.
    Other Name: monoclonal antibody
  • Experimental: Phase I
    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.
    Interventions:
    • Biological: milatuzumab
    • Biological: veltuzumab
    • Procedure: Correlative/Special Studies
    • Procedure: Quantitative T-, B-, and NK cell subsets
    • Procedure: Pharmacokinetics
    • Procedure: Pharmacokinetics
    • Procedure: Human Anti-Human Antibodies
  • Experimental: Phase II
    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.
    Intervention: Biological: veltuzumab and milatuzumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
36
March 2018
December 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00989586
OSU-09024, NCI-2011-03150
Yes
Beth Christian, Ohio State University Comprehensive Cancer Center
Beth Christian
Immunomedics, Inc.
Principal Investigator: Beth Christian, MD Ohio State University
Ohio State University Comprehensive Cancer Center
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP