Lenalidomide in Treating Young Patients With Relapsed or Refractory Solid Tumors or Myelodysplastic Syndromes

Study Overview
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Brief Summary
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This phase I trial is studying the side effects and best dose of lenalidomide in treating young patients with relapsed or refractory solid tumors or myelodysplastic syndromes. Lenalidomide may stop the growth of solid tumors or myelodysplastic syndromes by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose and recommended phase II dose of lenalidomide in pediatric patients with relapsed or refractory solid tumors. II. Determine the toxic effects of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients. SECONDARY OBJECTIVES: I. Determine, preliminarily, the feasibility of administering this drug to pediatric patients with relapsed or refractory myelodysplastic syndromes. II. Determine, preliminarily, the antitumor activity of this drug in both patient populations. III. Determine immunologic changes in patients treated with this drug. 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. PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Official Title
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Phase I Study of CC-5013 (Lenalidomide NSC# 703813) in Pediatric Patients With Relapsed/Refractory Solid Tumors or Myelodysplastic Syndrome

Conditions
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Childhood Myelodysplastic Syndromes, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Refractory Anemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Ringed Sideroblasts, Refractory Cytopenia With Multilineage Dysplasia, Secondary Myelodysplastic Syndromes, Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 acute myeloid leukemia (AML) No FAB diagnosis of refractory anemia with excess blasts in transition and other forms of AML Newly diagnosed MDS with chromosome 5q abnormalities Relapsed or refractory disease including relapse after stem cell transplantation 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 Performance status - Karnofsky 50-100% (for patients > 10 years of age) Performance status - Lansky 50-100% (for patients ≤ 10 years of age) Absolute neutrophil count ≥ 1,000/mm^3 (for patients with solid tumors) Platelet count ≥ 100,000/mm^3 (30,000 for patients with MDS) Only patients with MDS may receive transfusions to support platelet counts Hemoglobin ≥ 8.0 g/dL (transfusions allowed) Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT ≤ 110* Albumin ≥ 2 g/dL Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min 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) No parent or sibling with a known history of venous thrombosis before the age of 50 OR arterial thrombosis before the age of 40 No thromboembolic event except catheter-related thrombosis Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double-method contraception 4 weeks before, during, and for ≥ 4 weeks after completion of study treatment Body surface area ≥ 0.4m^2 No uncontrolled infection No active graft-vs-host disease from prior stem cell transplant or rescue 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 More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered No concurrent chemotherapy Concurrent dexamethasone allowed provided the dose has been either decreasing or stable for the past 7 days 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 No other concurrent investigational drugs or agents No other concurrent anticancer agents

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (lenalidomide)<br>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. | Drug: lenalidomide<br>* Given orally<br>* Other names: Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of lenolidomide defined as the maximum dose at which fewer than one-third of patients experience DLT | Graded using the CTCAE version 3.0. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response assessed using RECIST criteria | A patient will be considered to have responded if she or he demonstrates either a bone marrow or cytogenetic response. Each patient will be classified according to the maximum response of the two criteria, where the classification from maximum to minimum will be: CR, PR or nonresponse. | Up to 30 days after completion of study treatment | 
| Adverse events defined using the NCI CTCAE version 3.0 |  | Up to 30 days after completion of study treatment |