Oxaliplatin, Ifosfamide and Etoposide in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma

Refractory Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase I Trial of the Combination of Oxaliplatin (NSC 266046, IND 57004), Ifosfamide, and Etoposide in Recurrent or Refractory Pediatric Solid Tumors and Lymphomas

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00101205
• Other study ID #: NCI-2009-00075
• Secondary ID: NCI-2009-00075CD
• Status: Terminated
• Phase: Phase 1
• First received: January 7, 2005
• Last updated: February 21, 2014
• Start date: November 2004

Study information

• Verified date: April 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase I trial is studying the side effects and best dose of oxaliplatin and etoposide in treating young patients with recurrent or refractory solid tumors or lymphomas. Drugs used in chemotherapy, such as oxaliplatin and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Oxaliplatin may also help etoposide work better by making cancer cells more sensitive to the drug. Giving oxaliplatin together with etoposide may kill more cancer cells.

Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of oxaliplatin and etoposide in pediatric patients with recurrent or refractory solid tumors or lymphoma.

II. Determine the dose-limiting toxic effects of this regimen in these patients.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetic profile of this regimen in these patients. II. Correlate the extent of oxaliplatin and etoposide exposure with toxic effects and therapeutic effects of this regimen in these patients.

III. Determine, preliminarily, the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oxaliplatin IV over 2 hours on day 1 and etoposide IV over 1 hour on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oxaliplatin and etoposide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

• Life expectancy > 8 weeks

• Albumin > 2 g/dL

• Histologically confirmed diagnosis of 1 of the following: solid tumor; histologic verification not required for brainstem tumors or optic pathway tumors; lymphoma; recurrent or refractory to conventional therapy OR no known effective therapy exists; bone marrow involvement allowed

• Performance Status: Karnofsky >= 50 % (patients > 10 years of age) OR Lansky >= 50% (patients for =< 10 years of age)

• Absolute neutrophil count > 1,000/mm^3

• Platelet count > 100,000/mm^3 (transfusion independent)

• Hemoglobin > 8 g/dL (transfusion allowed)

• ALT < 5.0 times ULN

• Creatinine normal OR glomerular filtration rate >= 80 mL/min/1.73 m^2

• Calcium normal (electrolyte supplements allowed)

• Echocardiogram and EKG normal

• Shortening fraction >= 27% OR ejection fraction > 50%

• No evidence of dyspnea at rest

• No exercise intolerance

• Pulse oximetry > 94% on room air

• Neurologic deficits due to CNS tumor must be relatively stable for >= 2 weeks before study entry

• Seizure disorder allowed provided well-controlled by non-enzyme-inducing anticonvulsants

• No peripheral neurotoxicity > grade 1

• Sodium, potassium, and magnesium normal (electrolyte supplements allowed)

• At least 1 week since prior biologic agents

• More than 1 week since prior growth factors

• More than 6 months since prior allogeneic peripheral blood stem cell transplantation AND no active graft-versus-host disease

• More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)

• More than 2 weeks since prior focal radiotherapy for symptomatic metastatic sites

• More than 6 weeks since prior substantial bone marrow radiotherapy

• More than 3 months since prior craniospinal (> 24 Gy), whole pelvis, or total-body radiotherapy

• Recovered from all prior therapy

• No concurrent enzyme-inducing anticonvulsants, including, but not limited to, the following: Barbiturates; Phenytoin; Carbamazepine

Exclusion Criteria:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No uncontrolled infection

• No history of life-threatening hypersensitivity to platinum-containing agents

• No prior oxaliplatin

• No other concurrent investigational agents

• No other concurrent anticancer therapy

• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angioimmunoblastic T-cell Lymphoma
• B-cell Childhood Acute Lymphoblastic Leukemia
• B-cell Chronic Lymphocytic Leukemia
• Burkitt Lymphoma
• Childhood Burkitt Lymphoma
• Childhood Diffuse Large Cell Lymphoma
• Childhood Grade III Lymphomatoid Granulomatosis
• Childhood Immunoblastic Large Cell Lymphoma
• Childhood Nasal Type Extranodal NK/T-cell Lymphoma
• Hepatosplenic T-cell Lymphoma
• Hodgkin Disease
• Intraocular Lymphoma
• Leukemia
• Leukemia, Hairy Cell
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Extranodal NK-T-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral
• Lymphomatoid Granulomatosis
• Mycosis Fungoides
• Noncutaneous Extranodal Lymphoma
• Peripheral T-cell Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Childhood Acute Lymphoblastic 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
• Sezary Syndrome
• Small Intestine Lymphoma
• T-cell Childhood Acute Lymphoblastic Leukemia
• T-cell Large Granular Lymphocyte Leukemia
• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• oxaliplatin
Given IV
• etoposide
Given IV

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD of the combination of oxaliplatin and etoposide assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0		21 days	Yes
Primary	MTD of the addition of ifosfamide to the combination of oxaliplatin and etoposide assessed by CTCAE version 3.0		21 days	Yes