Flavopiridol in Treating Children With Relapsed or Refractory Solid Tumors or Lymphomas

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00012181

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of flavopiridol in treating children who have relapsed or refractory solid tumors or lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Childhood Brain Stem Glioma Recurrent Childhood Cerebellar Astrocytoma Recurrent Childhood Cerebral Astrocytoma Recurrent Childhood Ependymoma Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Liver Cancer Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Malignant Germ Cell Tumor Recurrent Childhood Medulloblastoma Recurrent Childhood Rhabdomyosarcoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Childhood Soft Tissue Sarcoma Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor Recurrent Childhood Visual Pathway and Hypothalamic Glioma Recurrent Childhood Visual Pathway Glioma Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Recurrent Neuroblastoma Recurrent Osteosarcoma Recurrent Retinoblastoma Recurrent Wilms Tumor and Other Childhood Kidney Tumors Recurrent/Refractory Childhood Hodgkin Lymphoma Unspecified Childhood Solid Tumor, Protocol Specific	Drug: alvocidib Other: pharmacological study	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

Determine the maximum tolerated dose of flavopiridol in children with relapsed or refractory solid tumors or lymphomas.
Determine the toxic effects and pharmacokinetics of this drug in these patients.
Determine the antitumor activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive flavopiridol IV over 1 hour on days 1-3. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3 to 6 patients receive escalating doses of flavopiridol 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.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 18 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A PHASE I STUDY OF FLAVOPIRIDOL (NSC# 649890; IND# 46211) IN PATIENTS WITH RELAPSED OR REFRACTORY PEDIATRIC SOLID TUMORS OR LYMPHOMAS

Study Start Date :

Apr 1, 2001

Actual Primary Completion Date :

Jan 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (alvocidib) Patients receive flavopiridol IV over 1 hour on days 1-3. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: alvocidib Given IV Other Names: FLAVO flavopiridol HMR 1275 L-868275 Other: pharmacological study Correlative studies Other Names: pharmacological studies

Arm

Intervention/Treatment

Experimental: Treatment (alvocidib)

Patients receive flavopiridol IV over 1 hour on days 1-3. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: alvocidib

Given IV

Other Names:

FLAVO

flavopiridol

HMR 1275

L-868275

Other: pharmacological study

Correlative studies

Other Names:

pharmacological studies

Outcome Measures

Primary Outcome Measures

MTD defined as the dose at which fewer than one-third of patients experience DLT assessed using Common Toxicity Criteria version 2.0 [Day 21]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed relapsed or refractory solid tumor or lymphoma including:
Neuroblastoma
Osteosarcoma
Ewing's sarcoma
Rhabdomyosarcoma
Wilms tumor
CNS tumors
Histological verification not required for brainstem tumors
No acute leukemia
Not eligible for higher priority COG phase I/II study
Performance status - Karnofsky 50-100% (over age 10)
Performance status - Lansky 50-100% (age 10 and under)
At least 2 months
Absolute neutrophil count at least 1,000/mm^3
Platelet count at least 75,000/mm^3 (transfusion independent)
Hemoglobin at least 8.0 g/dL (transfusion allowed)
No granulocytopenia, anemia, and/or thrombocytopenia due to bone marrow involvement
Bilirubin no greater than 1.5 times normal
SGPT no greater than 5 times normal
Albumin at least 2 g/dL
Creatinine no greater than 1.5 times normal
Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal
Shortening fraction at least 27% by echocardiogram
Ejection fraction at least 50% by MUGA
Stable neurologic deficits within the past 2 weeks for patients with CNS tumors
CNS toxicity less than grade 2
No active graft-versus-host disease
No active uncontrolled infection or other serious medical condition
No uncontrolled diabetes mellitus
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
At least 7 days since prior biologic therapy and recovered
Prior bone marrow or stem cell transplantation allowed
At least 6 months since prior allogeneic stem cell transplantation
At least 1 week since prior growth factors
No concurrent immunomodulating agents
At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
No other concurrent chemotherapy
Concurrent dexamethasone for CNS tumors allowed if on stable dose for at least 2 weeks prior to study
Concurrent corticosteroids allowed only for increased intracranial pressure in patients with CNS tumors
At least 2 weeks since prior local (small port) palliative radiotherapy
At least 6 months since prior radiotherapy to 50% or more of the pelvis
At least 6 months since prior craniospinal radiotherapy
At least 6 weeks since other prior substantial bone marrow radiotherapy
Recovered from prior radiotherapy
No concurrent radiotherapy except localized palliative radiotherapy
No concurrent anticonvulsants