Clinical trial NCT00243087: Investigation of Safety, Tolerability and Maximum Tolerated Dose (MTD) of BI 2536 in Patients With Recurrent Advanced Aggressive Non-Hodgkin's Lymphoma (NHL)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Keywords: stage IV adult diffuse large cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
stage IV grade 3 follicular lymphoma
recurrent grade 3 follicular lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
recurrent adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
anaplastic large cell lymphoma
recurrent adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult T-cell leukemia/lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-10-21
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose as measured by CTCAE v3.0 at days 1-22 of each course
timeFrame: up to 22 days of each course
measure: Dose-limiting toxicity as measured by CTCAE v3.0 at days 1-22 of each course
timeFrame: up to 22 days of each course
Secondary outcomes:
measure: Objective tumor response by CT scan or MRI as measured by RECIST criteria on day 22 of each even numbered course
timeFrame: day 22 of every second course
measure: Pharmacokinetics as measured in blood samples at days 1, 2, 3, and 8 during first course and on day 1 of each subsequent course
timeFrame: day 22 of each course
Other outcomes:
Locations:
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
Study officials:
affiliation: University of Nebraska
name: Julie M. Vose, MD
role: STUDY_CHAIR
References: