A Safety Study in Patients With Chronic Lymphocytic Leukemia

December 17, 2014 updated by: Seagen Inc.

A Phase 1/2, Multi-Dose Study of SGN-40 (Anti-huCD40 mAb) in Patients With Chronic Lymphocytic Leukemia

This is an open-label, dose-escalation study to determine the tolerability, safety profile, and antitumor activity of SGN-40 in patients with CLL. All patients will receive dose escalation during the first two weeks regardless of cohort designation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A minimum of three patients will be entered into each dose-level cohort for five weeks. Escalation to the next cohort will occur when three patients have received at least one infusion at the highest scheduled dose level, and at least one patient has completed the entire five week dosing schedule. Cohorts will be enrolled at a maximal dose level of 3, 4, 6, or 8 mg/kg/week. Initial therapy will last for 5 weeks. Responding patients will receive additional infusions every two weeks x 4 at the maximal dose for each specific cohort.

Study Type

Interventional

Enrollment (Actual)

12

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
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami, Sylvester Comprehensive Cancer Center
    • New York
      • New York, New York, United States, 10021
        • Weill Medical College/Cornell University
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research 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:

  1. Patients must have a histologic diagnosis of CLL as defined by the WHO criteria and exhibit active disease requiring treatment as per the NCI working group on CLL.
  2. Patients must have a fresh tumor specimen available (peripheral blood or bone marrow) for flow cytometry evaluation (e.g. CD40, CD38, CD20, CD19, and CD5).For the phase 2 portion of the study, CD40 expression on malignant cells must be confirmed prior to registration.

  3. Patients must have relapsed after receiving at least one fludarabine containing regimen or an equivalent purine analog.

    At study start patients must be at least 8 weeks or 5 plasma half-lives (whichever is greater) from prior chemotherapy/radiation/investigational agents, 8 weeks from prior antibody therapy and 6 months from autologous stem cell transplant.

  4. Patients must have an ECOG performance status ≤ 2 and a life expectancy > 3 months.

  5. Patients must have the following required baseline laboratory data:

    • Platelet count ≥ 50,000/mm3 (may be maintained by transfusion)
    • Hemoglobin ≥ 7.5 g/dL (may be maintained by transfusions or growth factors)
    • Absolute neutrophil count ≥ 1,000/mm3 (may be maintained by growth factors)
    • ALT/AST ≤ 2.0 times ULN
    • Total bilirubin ≤ 2.0 times ULN (unless related to hemolysis)
    • Creatinine < 2.0 times ULN
  6. Females of childbearing potential must have a negative B-hCG pregnancy test result within 3 days prior to the first dose and must agree to use an effective contraceptive method during the course of the study and for 6 months following the last dose of study drug.
  7. If a deep venous thrombosis or other vascular event has required medical or surgical intervention in the past year, patients must either: a) be on a stable dose of anticoagulant therapy (i.e., Coumadin and/or Heparin) for at least three weeks or b) have completed anticoagulant therapy at least three months prior to registration with radiographic confirmation that thrombosis is resolved. Prophylactic anticoagulant therapy for indwelling catheters is acceptable.
  8. Patients must be at least 18 years of age.
  9. Patients must be available for periodic blood sampling, study-related assessments, and management of toxicity at the treating institution.
  10. Patients must give written informed consent. A copy of the signed informed consent form will be retained by the treating institution.

Exclusion Criteria:

  1. Patients who have been treated previously with any anti-CD40 antibody.
  2. Patients with a documented history within 6 months of registration of a cerebral vascular event (stroke or TIA), unstable angina, or myocardial infarction.
  3. Patients with active CNS or leptomeningeal disease.
  4. Patients who have received allogeneic stem cell transplant.
  5. Patients who have had major surgery within four weeks prior to enrollment.
  6. Patients with a known hypersensitivity to recombinant proteins or any excipient contained in the drug formulation.
  7. Patients with a history of another primary malignancy that has not been in remission for at least 5 years (non-melanoma skin cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear are exempt from the five year limit).
  8. Patients with any systemic viral, bacterial, or fungal infection that has required antibiotic therapy within four weeks prior to enrollment. Prophylactic antibiotics and antiviral therapy are permitted prior to registration and are required during the study period (e.g. Bactrim, acyclovir).
  9. Patients with known HIV, hepatitis B (by surface antigen expression), or active hepatitis C infection.
  10. Patients on systemic steroids who have not been on a stable daily dose during the four weeks immediately prior to first dose of SGN-40. Maximum steroid dose is 10 mg prednisone per day or equivalent.
  11. Patients with a history of migraines or severe headaches requiring medical therapy (other than occasional acetaminophen, aspirin, or non-steroidal anti-inflammatory drugs) within 12 months of enrollment.
  12. Patients who are pregnant or breastfeeding.
  13. Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment.
  14. Patients with dementia or altered mental status that would preclude the understanding and/or rendering of informed consent.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
SGN-40
Drug: SGN-40 (anti-huCD40 mAb)
1-8 mg/kg IV; Days 1, 4, 8, 15, 22, 29 of Cycle 1 and Days 1, 15, 29 and 43 of Cycles 2-6.
Other Names:
  • dacetuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To determine the maximum tolerated dose (MTD) of multiple doses of SGN-40
To evaluate the safety profile, immunogenicity, and pharmacokinetics of SGN-40
To test the antitumor activity of SGN-40 in patients with CLL who have demonstrated recurrence or progression after at least one systemic therapy

Collaborators and Investigators

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

Sponsor

Seagen Inc.

Collaborators

Genentech, Inc.

Investigators

  • Study Director: Jonathan Drachman, MD, Seagen Inc.

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

Helpful Links

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

July 1, 2005

Primary Completion (Actual)

October 1, 2006

Study Completion (Actual)

October 1, 2006

Study Registration Dates

First Submitted

January 25, 2006

First Submitted That Met QC Criteria

January 25, 2006

First Posted (Estimate)

January 27, 2006

Study Record Updates

Last Update Posted (Estimate)

December 18, 2014

Last Update Submitted That Met QC Criteria

December 17, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SG040-0003

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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