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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
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: milatuzumab
Biological: veltuzumab
Procedure: Correlative/Special Studies
Procedure: Quantitative T-, B-, and NK cell subsets
Procedure: Pharmacokinetics
Procedure: Human Anti-Human Antibodies
Biological: veltuzumab and milatuzumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 36
Study Start Date: September 2009
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00989586

Locations
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Beth Christian
Immunomedics, Inc.
Investigators
Principal Investigator: Beth Christian, MD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Beth Christian, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00989586     History of Changes
Other Study ID Numbers: OSU-09024, NCI-2011-03150
Study First Received: October 2, 2009
Last Updated: September 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:
recurrent mantle cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
recurrent marginal zone lymphoma
Waldenstrom macroglobulinemia

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies
Antibodies, Monoclonal
Immunoglobulins
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014