Alemtuzumab With or Without Methotrexate and Mercaptopurine in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00089349

Purpose

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.

Condition	Intervention	Phase
Leukemia	Drug: alemtuzumab Drug: mercaptopurine Drug: methotrexate	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Mercaptopurine 6-Mercaptopurine Methotrexate Alemtuzumab Campath

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Study Of Campath-1H In Children With Acute Lymphoblastic Leukemia In Second or Greater Relapse or Twice Induction Failure

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Complete or partial response to alemtuzumab at day 29 of study therapy [ Designated as safety issue: No ]

Secondary Outcome Measures:

Complete or partial response to combination therapy at day 48 of study therapy [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	July 2004

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

Ages Eligible for Study:	up to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00089349

Show 29 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Anne Angiolillo, MD	Childrens Research Institute
Investigator:	Alice L. Yu, MD, PhD	University of California, San Diego

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000378240, COG-ADVL0222, NCI-05-C-0248
Study First Received:	August 4, 2004
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00089349
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

recurrent childhood acute lymphoblastic leukemia

Study placed in the following topic categories:

Folic Acid
Lymphatic Diseases
Leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma

Alemtuzumab
Methotrexate
6-Mercaptopurine
Lymphoproliferative Disorders
Lymphoma
Recurrence

Additional relevant MeSH terms:

Antimetabolites
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Reproductive Control Agents

Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Abortifacient Agents
Antirheumatic Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 14, 2009