Alemtuzumab With or Without Methotrexate and Mercaptopurine in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia
Intervention: alemtuzumab (Drug); mercaptopurine (Drug); methotrexate (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Children's Oncology Group Official(s) and/or principal investigator(s):
Anne Angiolillo, MD, Study Chair, Affiliation: Childrens Research Institute
Alice L. Yu, MD, PhD, Affiliation: University of California, San Diego
Summary
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: This phase II trial is studying how well giving alemtuzumab with or without
methotrexate and mercaptopurine works in treating young patients with relapsed acute
lymphoblastic leukemia.
Clinical Details
Official title: A Phase II Study Of Campath-1H In Children With Acute Lymphoblastic Leukemia In Second or Greater Relapse or Twice Induction Failure
Study design: Treatment, Open Label
Primary outcome: Complete or partial response to alemtuzumab at day 29 of study therapy
Secondary outcome: Complete or partial response to combination therapy at day 48 of study therapy
Detailed description:
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 greater
relapse or twice induction failure.
- 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, 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
PROJECTED ACCRUAL: A total of 10-25 patients will be accrued for this study within 2. 5
years.
Eligibility
Minimum age: N/A.
Maximum age: 30 Years.
Gender(s): Both.
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
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)
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
Locations and Contacts
Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States
Children's Hospital and Health Center - San Diego, San Diego, California 92123-4282, United States
Children's Hospital of Orange County, Orange, California 92868, United States
Stanford Comprehensive Cancer Center - Stanford, Stanford, California 94305, United States
Children's Hospital Cancer Center, Denver, Colorado 80218-1088, United States
Children's National Medical Center, Washington, District of Columbia 20010-2970, United States
University of Florida Shands Cancer Center, Gainesville, Florida 32610-0232, United States
Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States
Indiana University Cancer Center, Indianapolis, Indiana 46202-5289, United States
Kosair Children's Hospital, Louisville, Kentucky 40232, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States
University of Minnesota Medical Center & Children's Hospital - Fairview, Minneapolis, Minnesota 55455, United States
University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States
Overlook Hospital, Morristown, New Jersey 07962, United States
Herbert Irving Comprehensive Cancer Center at Columbia University, New York, New York 10032, United States
SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States
Columbus Children's Hospital, Columbus, Ohio 43205-2696, United States
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-9786, United States
Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada
St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States
Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-6310, United States
Baylor University Medical Center - Houston, Houston, Texas 77030-2399, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390, United States
Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States
Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: July 2004
Last updated: May 23, 2008
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