Trials / Terminated
TerminatedNCT00933985
Obatoclax Mesylate, Vincristine Sulfate, Doxorubicin Hydrochloride, and Dexrazoxane Hydrochloride in Treating Young Patients With Relapsed or Refractory Solid Tumors, Lymphoma, or Leukemia
A Phase I Study of Obatoclax (Pan Anti-Apoptotic BCL-2 Family Small Molecule Inhibitor), in Combination With Vincristine/Doxorubicin/Dexrazoxane, in Children With Relapsed/Refractory Solid Tumors or Leukemia
- Status
- Terminated
- Phase
- Phase 1
- Study type
- Interventional
- Enrollment
- 22 (actual)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 21 Years
- Healthy volunteers
- Not accepted
Summary
This phase I trial is studying the side effects and best dose of obatoclax mesylate when given together with vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride in treating young patients with relapsed or refractory solid tumors, lymphoma, or leukemia. Obatoclax mesylate may stop the growth of cancer cells by blocking some of the proteins needed for cell growth and causing the cells to self-destruct. Drugs used in chemotherapy, such as vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving obatoclax mesylate together with combination chemotherapy may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase II dose of obatoclax (obatoclax mesylate) administered as a single agent on day 1 and in combination with vincristine ( vincristine sulfate), doxorubicin (doxorubicin hydrochloride), and dexrazoxane (dexrazoxane hydrochloride) at day 8 in children with refractory solid tumors. II. To define and describe the toxicities of obatoclax administered on this schedule. III. To characterize the pharmacokinetics of obatoclax in children with refractory solid tumors or relapsed leukemia. SECONDARY OBJECTIVES: I. To preliminarily define the antitumor activity of obatoclax in children with refractory or relapsed solid tumors and leukemias within the confines of a Phase I study. II. To preliminarily assess leukemic blast characteristics associated with obatoclax activity. III. To preliminarily assess the biological activity of obatoclax by investigating effects on cell death regulatory pathways. OUTLINE: This is a dose-escalation study of obatoclax mesylate. STRATUM 1 (dose-escalation): Patients receive obatoclax mesylate intravenously (IV) over 3 hours on days 1 and 8 and vincristine sulfate IV, doxorubicin hydrochloride IV, and dexrazoxane hydrochloride IV on day 8 of course 1 (28 days). Drugs are administered on day 1 of subsequent courses and repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. STRATUM 2: Patients receive obatoclax mesylate (at starting dose in stratum 1), vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride as in stratum 1. STRATUM 3: Patients receive obatoclax mesylate (at the MTD determined in stratum 1), vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride as in stratum 1. After completion of study therapy, patients are followed up for 30 days.
Conditions
- Acute Leukemias of Ambiguous Lineage
- Acute Undifferentiated Leukemia
- Angioimmunoblastic T-cell Lymphoma
- Blastic Phase Chronic Myelogenous Leukemia
- Childhood Burkitt Lymphoma
- Childhood Chronic Myelogenous Leukemia
- Childhood Diffuse Large Cell Lymphoma
- Childhood Immunoblastic Large Cell Lymphoma
- Childhood Nasal Type Extranodal NK/T-cell Lymphoma
- Cutaneous B-cell Non-Hodgkin Lymphoma
- Hepatosplenic T-cell Lymphoma
- Intraocular Lymphoma
- Noncutaneous Extranodal Lymphoma
- Peripheral T-cell Lymphoma
- Recurrent Childhood Acute Lymphoblastic Leukemia
- Recurrent Childhood Acute Myeloid Leukemia
- Recurrent Childhood Anaplastic Large Cell Lymphoma
- Recurrent Childhood Grade III Lymphomatoid Granulomatosis
- Recurrent Childhood Large Cell Lymphoma
- Recurrent Childhood Lymphoblastic Lymphoma
- Recurrent Childhood Small Noncleaved Cell Lymphoma
- Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
- Recurrent Mycosis Fungoides/Sezary Syndrome
- Recurrent/Refractory Childhood Hodgkin Lymphoma
- Refractory Chronic Lymphocytic Leukemia
- Refractory Hairy Cell Leukemia
- Relapsing Chronic Myelogenous Leukemia
- Small Intestine Lymphoma
- Unspecified Childhood Solid Tumor, Protocol Specific
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | dexrazoxane hydrochloride | Given IV |
| DRUG | doxorubicin hydrochloride | Given IV |
| DRUG | obatoclax mesylate | Given IV |
| DRUG | liposomal vincristine sulfate | Given IV |
| OTHER | pharmacological study | Correlative studies |
| OTHER | laboratory biomarker analysis | Correlative studies |
Timeline
- Start date
- 2009-06-01
- Primary completion
- 2013-04-01
- Completion
- 2013-04-01
- First posted
- 2009-07-08
- Last updated
- 2014-05-01
Locations
20 sites across 2 countries: United States, Canada
Source: ClinicalTrials.gov record NCT00933985. Inclusion in this directory is not an endorsement.