Ewing's Sarcoma

ADVL0319: A Phase I Study of CC-5013 in Pediatric Patients with Relapsed / Refractory Solid Tumors or Myelodysplastic Syndrome

Date Last Modified: 06-12-2006
Date First Published: 03-28-2005

TypeStatusAge Range (yrs.)SponsorProtocol ID
Treatment Active 1-21 COG ADVL0319

Outline

This is a dose-escalation, multicenter study. Patients are stratified according to diagnosis (solid tumor vs myelodysplastic syndromes [MDS]).

Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients with solid tumors receive escalating doses of lenalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients with MDS receive a fixed dose (do not undergo dose escalation) of lenalidomide.

After completion of study treatment, patients are followed annually.

Objectives

Primary

  1. Determine the maximum tolerated dose and recommended phase II dose of lenalidomide in pediatric patients with relapsed or refractory solid tumors.
  2. Determine the toxic effects of this drug in these patients.
  3. Determine the pharmacokinetics of this drug in these patients.

Secondary

  1. Determine, preliminarily, the feasibility of administering this drug to pediatric patients with relapsed or refractory myelodysplastic syndromes.
  2. Determine, preliminarily, the antitumor activity of this drug in both patient populations.
  3. Determine immunologic changes in patients treated with this drug.

Projected Accrual

Approximately 3-52 patients (3-42 with solid tumors and up to 10 with myelodysplastic syndromes) will be accrued for this study within 1-17 months.

Entry Criteria

Disease Characteristics:

  • Diagnosis of 1 of the following:
    • Histologically confirmed solid tumor
      • No brain tumors
    • Myelodysplastic syndromes (MDS)
      • No refractory anemia with excess blasts in transformation or other forms of AML
      • NO FAB diagnosis or refractory anemia with excess blasts in transition and other forms of AML
      • Newly diagnosed MDS with chromosome 5q abnormalities
  • Measurable or evaluable disease (solid tumor patients only)
  • No known curative or life-prolonging therapy exists
  • No bone marrow involvement by tumor (solid tumor patients only)
  • No CNS tumors
  • Relapsed or refractory disease including relapse after stem cell transplantation

Prior / Concurrent Therapy:

Biologic therapy

  • Recovered from prior immunotherapy
  • At least 1 week since prior biologic agents
  • At least 1 week since prior hematologic growth factors (2 weeks for pegfilgrastim)
  • At least 3 months since prior stem cell transplant or rescue (without total body irradiation [TBI])
  • Prior thalidomide allowed
  • No other concurrent immunotherapy
  • No other concurrent biologic therapy

Chemotherapy

  • More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
  • No concurrent chemotherapy

Endocrine therapy

  • Concurrent dexamethasone allowed provided the dose has been either decreasing or stable for the past 7 days

Radiotherapy

  • See Biologic therapy
  • Recovered from prior radiotherapy
  • At least 2 weeks since prior local palliative (small port) radiotherapy
  • At least 6 months since prior TBI, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis
  • At least 6 weeks since other prior substantial bone marrow radiotherapy
  • No concurrent radiotherapy

Surgery

  • Not specified

Other

  • No other concurrent investigational drugs or agents
  • No other concurrent anticancer agents

Patient Characteristics:

Age

  • 1 to 21

Performance status

  • Karnofsky 50-100% (for patients > 10 years of age)
  • Lansky 50-100% (for patients ≤ 10 years of age)

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm3 (for patients with solid tumors)
  • Platelet count ≥ 100,000/mm3 (30,000 for patients with MDS)
    • Only patients with MDS may receive transfusions to support platelet counts
  • Hemoglobin ≥ 8.0 g/dL (transfusions allowed)

      • Hepatic

      • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
      • ALT ≤ 5 times ULN
      • Albumin ≥ 2 g/dL 

      Renal

      • Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min

      OR

      • Creatinine based on age as follows:
        • Creatinine ≤ 0.8 mg/dL (for patients ≤ 5 years of age)
        • Creatinine ≤ 1 mg/dL (for patients 6 to 10 years of age)
        • Creatinine ≤ 1.2 mg/dL (for patients 11 to 15 years of age)
        • Creatinine ≤ 1.5 mg/dL (for patients over 15 years of age)

          Cardiovascular

          • No parent or sibling with a known history of venous thrombosis before the age of 50 OR thrombosis before the age of 40
          • No thromboembolic event except catheter-related thrombosis

          Other

          • Not pregnant or nursing
          • Negative pregnancy test
          • Fertile patients must use effective contraception
          • Body surface area ≥ 0.4m2
          • No uncontrolled infection
          • No active graft-vs-host disease from prior stem cell transplant or rescue

          Who should I contact for more information?

          Rebecca Turner, CCRP
          Cincinnati Children's Hospital Medical Center
          Department of Hematology / Oncology
          3333 Burnet Ave., Cincinnati, OH 45229-3039
          Phone:  513-636-2799
          cancer@cchmc.org