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

August 12, 2021 updated by: Gilead Sciences

Phase I/II Study of Veltuzumab Combined With 90Y-Epratuzumab Tetraxetan in Patients With Relapsed/Refractory, Aggressive Non- Hodgkin's Lymphoma

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Delaware
      • Newark, Delaware, United States, 19713
        • Helen F. Graham Cancer Center
    • Florida
      • Orlando, Florida, United States, 32806
        • MDACC Orlando
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Indiana
      • Goshen, Indiana, United States, 46526
        • Goshen Center for Cancer Care
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10021
        • Weill Med College of Cornell Univ/NYH
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • IMMU-106
  • hA20
  • veltuzumab
  • 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:
  • IMMU-106
  • hA20
  • humanized CD20
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety/dose limiting toxicity
Time Frame: 12 weeks
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.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy
Time Frame: 12 weeks-5 years

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.
12 weeks-5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 1, 2010

Primary Completion (ACTUAL)

December 1, 2016

Study Completion (ACTUAL)

March 1, 2017

Study Registration Dates

First Submitted

March 16, 2010

First Submitted That Met QC Criteria

April 8, 2010

First Posted (ESTIMATE)

April 12, 2010

Study Record Updates

Last Update Posted (ACTUAL)

August 18, 2021

Last Update Submitted That Met QC Criteria

August 12, 2021

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IM-T-hA20/90Y-hLL2-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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