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

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

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.

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.

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