RATIONALE: Monoclonal antibodies such as alemtuzumab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as methotrexate and mercaptopurine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of alemtuzumab with or without methotrexate and mercaptopurine in treating young patients who have relapsed acute lymphoblastic leukemia.

Condition	Treatment or Intervention	Phase
recurrent childhood acute lymphoblastic leukemia	Drug: alemtuzumab  Drug: mercaptopurine  Drug: methotrexate  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy	Phase II

OBJECTIVES: Primary

• Determine the response rate to alemtuzumab alone and in combination with methotrexate and mercaptopurine in children with acute lymphoblastic leukemia in second or refractory relapse.
• Determine the toxicity of these regimens in these patients.

Secondary

• Determine the pharmacokinetics of alemtuzumab in these patients.
• Determine the immune response in patients treated with alemtuzumab.
• Determine changes in the number of CD52-positive cells in the blood and marrow of patients treated with alemtuzumab.
• Determine the rate and timing of clearance of peripheral circulating lymphoblasts in patients treated with these regimens.

OUTLINE: This is a multicenter study.

• Course 1: Patients receive alemtuzumab IV over 2 hours on days 1-5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission (CR), partial remission (PR), or cytolytic PR at day 29 proceed to course 2.
• Courses 2 and 3: Patients receive alemtuzumab IV over 2 hours on days 1, 8, 15, and 22; methotrexate IV continuously over 24 hours on day 1 and then orally once daily on days 8, 15, and 22; and oral mercaptopurine once daily on days 1-28. Patients with a CR or PR at day 29 proceed to course 3. In course 3, patients receive alemtuzumab, methotrexate, and mercaptopurine as in course 2.
• CNS prophylaxis: Patients receive methotrexate intrathecally on day 15 of course 1 and on day 1 of courses 2 and 3.

PROJECTED ACCRUAL: A total of 10-25 patients will be accrued for this study within 2.5 years.

Ages Eligible for Study:  up to  21 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of acute lymphoblastic leukemia
• Meets 1 of the following criteria:
• Second or subsequent bone marrow relapse
• Failed ≥ 2 regimens for remission induction
• More than 25% blasts in bone marrow aspirate (M3 marrow)
• CD52 expression on ≥ 25% of malignant cells at relapse
• Philadelphia chromosome-positive patients must have failed prior imatinib mesylate
• No clinical evidence of extramedullary testicular disease
• No laboratory evidence of CNS disease

PATIENT CHARACTERISTICS: Age

• 21 and under

Performance status

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

Life expectancy

• At least 8 weeks

Hematopoietic

• Not specified

Hepatic

• ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
• Creatinine normal for age

Pulmonary

• Pulse oximetry > 94%
• No evidence of dyspnea at rest
• No exercise intolerance

Immunologic

• No serious uncontrolled infection
• No autoimmune hemolytic anemia
• No autoimmune thrombocytopenia

Other

• Not pregnant or nursing
• No nursing for 3 months after study participation
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation
• Seizure disorder allowed provided patients are on anticonvulsants and symptoms are well controlled
• CNS toxicity ≤ grade 2
• No other serious uncontrolled medical condition (e.g., diabetes)

PRIOR CONCURRENT THERAPY: Biologic therapy

• Recovered from prior immunotherapy
• At least 8 weeks since prior biologic agents (e.g., monoclonal antibodies)
• More than 1 week since prior growth factor(s)
• At least 4 months since prior stem cell transplantation
• No evidence of active acute or chronic graft-versus-host disease post allogeneic stem cell transplantation
• No prior alemtuzumab or its components
• No other concurrent anticancer immunomodulating agents

Chemotherapy

• One dose of prior intrathecal (IT) methotrexate, cytarabine, and hydrocortisone; IT cytarabine alone; or IT methotrexate alone allowed as part of initial diagnostic spinal tap
• More than 2 weeks since prior myelosuppressive chemotherapy and recovered
• No other concurrent anticancer chemotherapy agents

Endocrine therapy

• More than 2 weeks since prior steroids and recovered

Radiotherapy

• More than 2 weeks since prior radiotherapy and recovered

Surgery

• Not specified

California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States; Recruiting
      Lucile Packard Children's Hospital at Stanford University Medical Center, Palo Alto,  California,  94304,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States; Recruiting
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States; Recruiting
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States; Recruiting
Maryland
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States; Recruiting
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      University Hospital at State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States; Recruiting
Ohio
      Children's Hospital Medical Center of Akron, Akron,  Ohio,  44308-1062,  United States; Recruiting
Oregon
      Doernbecher Children's Hospital at Oregon Health & Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213-2583,  United States; Recruiting
Tennessee
      St. Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States; Recruiting
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-9063,  United States; Recruiting
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States; Recruiting
Canada, Ontario
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada; Recruiting
Canada, Quebec
      Hopital Sainte Justine, Montreal,  Quebec,  H3T 1C5,  Canada; Recruiting

Study chairs or principal investigators

Anne Angiolillo, MD,  Study Chair,  Children's National Medical Center   
Alice L. Yu, MD, PhD,  UCSD Cancer Center   

Study ID Numbers:  CDR0000378240; COG-ADVL0222
Record last reviewed:  July 2004
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00089349
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-08