Study of Veltuzumab and 90Y-Epratuzumab in Relapsed/Refractory, Aggressive NHL

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Immunomedics, Inc.
Sponsor:
Information provided by (Responsible Party):
Immunomedics, Inc.
ClinicalTrials.gov Identifier:
NCT01101581
First received: March 16, 2010
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

The goal of this study is to evaluate a new approach to immunotherapy in NHL by combining two antibodies, veltuzumab and epratuzumab. For treatment, epratuzumab has also been attached to a radioactive isotope called 90yttrium (90Y-epratuzumab). Veltuzumab and 90Y-epratuzumab attack different areas on lymphoma cells. Because of this, treatment with the combination may provide more effective treatment in NHL than either veltuzumab or 90Y-epratuzumab given alone.


Condition Intervention Phase
Non Hodgkin's Lymphoma
NHL
Aggressive NHL
Diffuse Large B-cell Lymphoma
Drug: Veltuzumab and 90Y-Epratuzumab Tetraxetan
Drug: 90Y-epratuzumab tetraxetan
Drug: veltuzumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Veltuzumab Combined With 90Y-Epratuzumab Tetraxetan in Patients With Relapsed/Refractory, Aggressive Non- Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Immunomedics, Inc.:

Primary Outcome Measures:
  • Safety/dose limiting toxicity [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Patients are closely monitored during and after all infusions, and then at intervals over a 12-week post-treatment evaluation period. Safety evaluations required in all patients include vital signs, physical examination, CBC, serum chemistries, serum immunoglobulins, urinalysis, peripheral blood B-cell levels (immunophenotyping based on CD19), and HAHA (to be analyzed by Sponsor). Adverse events and abnormal laboratories will be graded for toxicity according to NCI CTC v3.0 criteria.


Secondary Outcome Measures:
  • Efficacy [ Time Frame: 12 weeks-5 years ] [ Designated as safety issue: No ]

    CT or PET/CT imaging will be used to quantify changes in index lesions identified on baseline imaging, with responses classified according to revised response criteria for NHL (Cheson, 2007).

    Patients with stable disease or objective responses continue limited follow-up evaluations, including CT evaluations, physical examinations and serum laboratories every 3 months for the first year and then every 6 months up to a total of 5 years or until progression of disease.



Estimated Enrollment: 70
Study Start Date: May 2010
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Veltuzumab and 90Y-Epratuzumab Tetraxetan
Veltuzumab and 90Y-Epratuzumab Tetraxetan target different b-cells. Veltuzumab will be administered in all 4 weekly study drug treatments. 90Y-Epratuzumab Tetraxetan will be administered only on days 8 & 15. The dose of veltuzumab remains the same for all patients.
Drug: Veltuzumab and 90Y-Epratuzumab Tetraxetan
Veltuzumab will be administered subcutaneously in phase 2. 90Y-Epratuzumab tetraxetan will be administered intravenously. Veltuzumab is given once weekly for 4 weeks. 90Y-Epratuzumab is also given at treatment weeks 2 & 3 (days 8 & 15).
Other Names:
  • veltuzumab
  • IMMU-106
  • hA20
  • humanized CD20
  • epratuzumab-tetraxetan
  • 90Y-hLL2
  • IMMU-102
  • humanized CD22
Drug: 90Y-epratuzumab tetraxetan
Other Names:
  • 90Y-hLL2
  • 90Y-hLL2-DOTA
  • 90Y-CD22
Drug: veltuzumab
Veltuzumab will be administered subcutaneously on days 1, 8, 15 and 23
Other Names:
  • hA20
  • humanized CD20
  • IMMU-106
Experimental: 90Y-epratuzumab tetraxetan
90Y-epratuzumab tetraxetan will be administered 6 mCi/m2 on days 8 and 15.
Drug: 90Y-epratuzumab tetraxetan
Other Names:
  • 90Y-hLL2
  • 90Y-hLL2-DOTA
  • 90Y-CD22

Detailed Description:

The treatment portion of this study consists of study drug administrations each week for four weeks in a row (a total of 4 treatment days). Patients will then return at intervals up to 12 weeks for blood samples and for evaluations to see if their disease responded and to monitor any adverse effects related to treatment. Some blood tests may then need to be repeated at least a few times and/or until any abnormal findings at earlier evaluations have resolved. Otherwise, patients will continue to be evaluated every 3 months for two years, then every 6 months up to 5 years or until the disease worsens. Participation in the study will end when NHL disease worsens.

  Eligibility

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

Inclusion Criteria:

  • Male or female, >18 years old
  • Histological diagnosis of CD20+ B-cell NHL, with DLBCL or other aggressive lymphomas by WHO lymphoma criteria including mantle cell lymphoma and transformed follicular lymphoma.
  • Failed at least one prior standard treatment regimen for NHL
  • If DLBCL, either received, ineligible for or refused high-dose chemotherapy with stem cell transplant
  • Measurable NHL disease by CT, with at least one lesion >1.5 cm in one dimension
  • Adequate performance status (>70 Karnofsky scale, 0-1 ECOG)* with an estimated life expectancy of at least 6 months
  • Laboratory parameters:

    • Adequate hematology (Hemoglobin >/= 10 g/dL, ANC >/= 1.5 ´ 109/L, platelets >/=100 x 109/L) without ongoing transfusional support
    • Adequate renal and liver function (creatinine and bilirubin </= 1.5 x IULN; AST and ALT </= 2.5 x IULN)
  • Otherwise, <Grade 1 toxicity at study entry by NCI CTC version 3.0.
  • 3 months beyond any prior rituximab or veltuzumab treatment, 12 weeks beyond autologous stem cell transplant and 4 weeks beyond chemotherapy, other experimental treatments, or any radiation therapy to the index lesion(s).
  • Screened for hepatitis B (no time limit) and negative by tests included in NCCN guidelines (hepatitis B surface antigen/antibodies, core antigen/antibodies, hepatitis B e-antigen).
  • Patients of childbearing potential must be willing to practice birth control during the study until at least 12 weeks after last veltuzumab infusion; women of childbearing potential must have a negative urine or serum pregnancy test to enter the study.
  • Ability to provide signed, informed consent

Exclusion Criteria:

  • Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test

    • NCI CTC Grade 3 or 4 infusion reaction to prior anti-CD20 antibodies (rituximab, veltuzumab, etc.)
    • A known anti-antibody response to prior antiCD20 antibodies (HACA positive, HAHA positive, etc)
    • Prior radioimmunotherapy, including Zevalin or Bexxar.
    • Prior high-dose chemotherapy with peripheral blood stem cell transplant.
    • Prior therapy with other human or humanized monoclonal antibodies, unless HAHA tested and negative
    • Primary CNS lymphoma, HIV lymphoma or transformed lymphoma, or presence of symptomatic CNS metastases or carcinomatous meningitis.
    • Rituximab or veltuzumab resistant, defined as having progressed during or within 6 months of any prior rituximab or veltuzumab treatment.
    • Bulky disease by CT, defined as any single mass >10 cm in its greatest diameter
    • Bone marrow involvement ≥25%
    • Prior external beam radiation therapy to >30% bone marrow.
    • Pleural effusion with positive cytology for lymphoma
    • Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive
    • Known autoimmune disease or presence of autoimmune phenomena.
    • Evidence of infection or requiring antibiotics within 7 days.
    • Use of systemic corticosteroids within 2 weeks, except low dose regimens (prednisone, <20 mg/day, or equivalent) which may continue if unchanged.
    • Prior malignancies (other than non-melanoma skin cancer or carcinoma in situ of the cervix) unless disease free for 5 years.
    • Prior malignancy with less than a 5-year disease-free interval, excluding nonmelanoma skin cancers and carcinoma in situ of the cervix.
    • Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations
  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: NCT01101581

Contacts
Contact: Michael Sosnowski (973) 727-4279 msosnowski@immunomedics.com
Contact: Fran Bozza 973-605-8200

Locations
United States, Delaware
Helen F. Graham Cancer Center Recruiting
Newark, Delaware, United States, 19713
Contact: Katie Alexander, RN       kalexander@christianacare.org   
United States, Florida
MDACC Orlando Recruiting
Orlando, Florida, United States, 32806
Contact: Casey Kulsar, RN       casey.kulscar@orlandohealth.com   
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Bonnie Sauder, RN       bonnie.sauder@moffitt.org   
Principal Investigator: Michael Tomblyn, MD         
United States, Indiana
Goshen Center for Cancer Care Recruiting
Goshen, Indiana, United States, 46526
Contact: Tracy Thorne, RN    574-364-2439    tthorne@iuhealth.com   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Jennifer Jensen, RN       jensen.jennifer@mayo.edu   
United States, New York
Weill Med College of Cornell Univ/NYH Recruiting
New York, New York, United States, 10021
Contact: Hannah Campbell       hac2012@med.cornell.edu   
United States, Pennsylvania
University of Pennsylvania Cancer Center Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Immunomedics, Inc.
Investigators
Study Chair: William Wegener, MD, PhD Immunomedics, Inc.
  More Information

Publications:
Responsible Party: Immunomedics, Inc.
ClinicalTrials.gov Identifier: NCT01101581     History of Changes
Other Study ID Numbers: IM-T-hA20/90Y-hLL2-01
Study First Received: March 16, 2010
Last Updated: December 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Immunomedics, Inc.:
Diffuse Large cell NHL
Mantle cell NHL
Lymphoblastic lymphoma
Diffuse mixed cell lymphoma
Diffuse large cell lymphoma
large noncleaved cell lymphoma

Additional relevant MeSH terms:
Aggression
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Behavioral Symptoms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014