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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00243087
• Other study ID #: CDR0000446176
• Secondary ID: BOEH-BI-1216.3UN
• Status: Completed
• Phase: Phase 1
• First received: October 20, 2005
• Last updated: October 31, 2013
• Start date: July 2005

Study information

• Verified date: October 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ukraine: State Expert Center of the Ministry of Health of Ukraine
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• BI 2536

Locations

Country	Name	City	State
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose as measured by CTCAE v3.0 at days 1-22 of each course		up to 22 days of each course	No
Primary	Dose-limiting toxicity as measured by CTCAE v3.0 at days 1-22 of each course		up to 22 days of each course	No
Secondary	Objective tumor response by CT scan or MRI as measured by RECIST criteria on day 22 of each even numbered course		day 22 of every second course	No
Secondary	Pharmacokinetics as measured in blood samples at days 1, 2, 3, and 8 during first course and on day 1 of each subsequent course		day 22 of each course	No