Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Alemtuzumab With or Without Methotrexate and Mercaptopurine in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	30 and under at diagnosis	NCI	COG-ADVL0222 ADVL0222, NCI-05-C-0248, NCT00089349

Objectives

Primary

1. Determine the response rate to alemtuzumab alone and in combination with methotrexate and mercaptopurine in children with acute lymphoblastic leukemia in second or greater relapse or twice induction failure.
2. Determine the toxicity of these regimens in these patients.

Secondary

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

Entry Criteria

Disease Characteristics:

• Diagnosis of acute lymphoblastic leukemia (ALL)
  • Meets 1 of the following criteria:
    • Second or subsequent bone marrow relapse
    • Failed ≥ 2 regimens for remission induction
      • Patients who relapse while receiving standard ALL maintenance chemotherapy do not require a waiting period prior to study entry
• 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

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

• Recovered from prior 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
• Prior hydroxyurea therapy allowed
• No other concurrent anticancer chemotherapy agents

Endocrine therapy

• Prior steroid therapy allowed

Radiotherapy

• More than 2 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Patient Characteristics:

Age

• 30 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 ≤ 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)

Expected Enrollment

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

Outcomes

Complete or partial response to alemtuzumab at day 29 of study therapy

Complete or partial response to combination therapy at day 48 of study therapy

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, or patients with CNS disease that achieve a CNS 1 or CNS 2 status, 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 1 of courses 2 and 3 on day 1 of courses 2 and 3.

   [Note: * CNS-negative patients receive methotrexate intrathecally on day 15 of course 1 and day 1 of courses 2 and 3]

Angiolillo AL, Yu AL, Reaman G, et al.: A phase II study of Campath-1H in children with relapsed or refractory acute lymphoblastic leukemia: a Children's Oncology Group report. Pediatr Blood Cancer 53 (6): 978-83, 2009.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Anne Angiolillo, MD, Protocol chair		Ph: 202-476-5000
Alice Yu, MD, PhD, Protocol co-chair		Ph: 858-822-5354

Registry Information
Official Title		A Phase II Study Of Campath-1H In Children With Acute Lymphoblastic Leukemia In Second or Greater Relapse or Twice Induction Failure
Trial Start Date		2004-07-06
Registered in ClinicalTrials.gov		NCT00089349
Date Submitted to PDQ		2004-07-06
Information Last Verified		2006-12-13
NCI Grant/Contract Number		CA97452

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