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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00104962

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: lenalidomide	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2005

Actual Primary Completion Date :

Jun 1, 2009

Actual Study Completion Date :

Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (lenalidomide) 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 Given orally Other Names: CC-5013 IMiD-1 Revlimid

Arm

Intervention/Treatment

Experimental: Treatment (lenalidomide)

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

Given orally

Other Names:

CC-5013

IMiD-1

Revlimid

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of lenolidomide defined as the maximum dose at which fewer than one-third of patients experience DLT [28 days]
Graded using the CTCAE version 3.0.

Secondary Outcome Measures

Overall response assessed using RECIST criteria [Up to 30 days after completion of study treatment]
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.
Adverse events defined using the NCI CTCAE version 3.0 [Up to 30 days after completion of study treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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