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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Recurrent Childhood Medulloblastoma; Recurrent Neuroblastoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Osteosarcoma; Recurrent Childhood Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent Childhood Liver Cancer; Recurrent Retinoblastoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Unspecified Childhood Solid Tumor, Protocol Specific; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Rhabdomyosarcoma

Treatments: Drug: alvocidib; Other: pharmacological study

Study type: Interventional

Funder types: NIH

Identifiers

NCT00012181

NCI-2012-01854

COG-ADVL0017

NCI-A0972

CDR0000068491

CCG-AO972

ADVL0017

U01CA097452 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of flavopiridol in children with relapsed or refractory solid tumors or lymphomas.

II. Determine the toxic effects and pharmacokinetics of this drug in these patients.

III. 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.

Enrollment: 30 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Treatment (alvocidib)

Experimental group

Description:

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.

Treatment:

Other: pharmacological study

Drug: alvocidib