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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: BI 2536


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: BI 2536|nan|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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