Investigation of Safety, Tolerability and Maximum Tolerated Dose (MTD) of BI 2536 in Patients With Recurrent Advanced Aggressive Non-Hodgkin's Lymphoma (NHL)

October 31, 2013 updated by: Boehringer Ingelheim

An Open Phase I Single Dose Escalation Study of BI 2536 Administered Intravenously in Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma

RATIONALE: BI 2536 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of BI 2536 in treating patients with refractory or relapsed advanced non-Hodgkin's lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of BI 2536 in patients with refractory or relapsed advanced aggressive non-Hodgkin's lymphoma.
  • Determine the safety and tolerability of this drug in these patients.

Secondary

  • Determine the pharmacokinetic profile of this drug in these patients.
  • Determine, preliminarily, the antitumor activity of this drug in these patients.

OUTLINE: This is a dose-escalation, open-label, uncontrolled, multicenter study.

Patients receive BI 2536 IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of BI 2536 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity during the first treatment course. Up to 24 patients are treated at the MTD.

After completion of study treatment, patients are followed periodically until disease progression or initiation of another cancer treatment.

PROJECTED ACCRUAL: A maximum of 50 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • 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
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198-6805
        • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
    • New York
      • Rochester, New York, United States, 14642
        • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Texas
      • Houston, Texas, United States, 77030-4009
        • M. D. Anderson Cancer Center at University of Texas

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed advanced aggressive non-Hodgkin's lymphoma (NHL), including any of the following subtypes:

    • B-cell NHL, including any of the following subtypes:

      • Diffuse large B-cell lymphoma
      • Primary mediastinal (thymic) B-cell lymphoma
      • Intravascular large B-cell lymphoma
      • Immunoblastic B-cell lymphoma
      • Mantle cell lymphoma
      • Burkitt's lymphoma
      • Follicular grade 3b lymphoma

    • T-cell NHL, including any of the following subtypes:

      • Anaplastic large cell lymphoma
      • Peripheral T-cell lymphoma, not otherwise specified
  • De novo or transformed disease

  • Refractory (i.e., disease not amenable to standard therapy) or relapsed disease, as evidenced by 1 of the following:

    • Refractory to OR relapsed after ≥ 1 prior combination chemotherapy regimen
    • Refractory to OR relapsed after prior CD20-based immunotherapy (for patients eligible to receive such therapy)
    • Refractory after prior high-dose chemotherapy and autologous stem cell transplantation AND ≥ 100 days post transplantation
  • At least 1 bidimensionally measurable lesion ≥ 1.5 cm by CT scan, MRI, x-ray, or clinical examination
  • No active CNS lymphoma

PATIENT CHARACTERISTICS:

Performance status

  • ECOG 0-2

Life expectancy

  • At least 3 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • No known coagulopathy

Hepatic

  • ALT and/or AST ≤ 2.5 times upper limit of normal (ULN) (< 5 times ULN if due to hepatic lymphoma)
  • Bilirubin ≤ 1.5 times ULN

Renal

  • Creatinine ≤ 2.0 mg/dL

Immunologic

  • No known HIV infection
  • No serious active infection that requires IV antibiotics or antifungal or antiviral agents

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception during and for 1 year after completion of study treatment
  • No known or suspected alcohol or drug abuse
  • No sensory or motor neuropathy ≥ grade 3
  • No other malignancy within the past 5 years except nonmelanoma skin cancer
  • No other life-threatening illness or organ dysfunction that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • See Radiotherapy
  • More than 3 weeks since prior and no concurrent immunotherapy
  • No prior allogeneic bone marrow transplantation

Chemotherapy

  • See Disease Characteristics
  • More than 3 weeks since prior and no concurrent chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

  • No concurrent hormonal therapy

Radiotherapy

  • No prior radiotherapy to the only site of measurable disease unless there is documented disease progression after completion of radiotherapy
  • More than 8 weeks since prior and no concurrent systemic radioimmunotherapy

  • More than 3 weeks since prior and no concurrent radiotherapy

    • Concurrent palliative radiotherapy to sites other than the only measurable target lesion allowed for symptom control provided the reason for radiotherapy does not reflect progressive disease

Other

  • No concurrent warfarin for therapeutic anticoagulation

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
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose as measured by CTCAE v3.0 at days 1-22 of each course
Time Frame: up to 22 days of each course
up to 22 days of each course
Dose-limiting toxicity as measured by CTCAE v3.0 at days 1-22 of each course
Time Frame: up to 22 days of each course
up to 22 days of each course

Secondary Outcome Measures

Outcome Measure
Time Frame
Objective tumor response by CT scan or MRI as measured by RECIST criteria on day 22 of each even numbered course
Time Frame: day 22 of every second course
day 22 of every second course
Pharmacokinetics as measured in blood samples at days 1, 2, 3, and 8 during first course and on day 1 of each subsequent course
Time Frame: day 22 of each course
day 22 of each course

Collaborators and Investigators

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

Sponsor

Boehringer Ingelheim

Investigators

  • Study Chair: Julie M. Vose, MD, University of Nebraska

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)

August 1, 2008

Study Registration Dates

First Submitted

October 20, 2005

First Submitted That Met QC Criteria

October 20, 2005

First Posted (Estimate)

October 21, 2005

Study Record Updates

Last Update Posted (Estimate)

November 1, 2013

Last Update Submitted That Met QC Criteria

October 31, 2013

Last Verified

October 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000446176
  • BOEH-BI-1216.3
  • UNMC-16005

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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