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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00089349
First received: August 4, 2004
Last updated: June 4, 2013
Last verified: June 2013
  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. 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.


Condition Intervention Phase
Recurrent Childhood Acute Lymphoblastic Leukemia
Biological: alemtuzumab
Drug: methotrexate
Drug: mercaptopurine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Campath-1H in Children With Acute Lymphoblastic Leukemia in Second or Greater Relapse or Twice Induction Failure

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response rate to Campath-1H alone [ Time Frame: Day 29, course 1 ] [ Designated as safety issue: No ]
  • Response to combined treatment with Campath-1H and chemotherapy [ Time Frame: Day 29, course 2 ] [ Designated as safety issue: No ]
  • Tolerability of the combination therapy evaluated by dose-limiting toxicity [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: July 2004
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

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.

Biological: alemtuzumab
Given IV
Other Names:
  • anti-CD52 monoclonal antibody
  • Campath-1H
  • MoAb CD52
  • Monoclonal Antibody Campath-1H
  • Monoclonal Antibody CD52
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP

Detailed Description:

PRIMARY OBJECTIVES:

I. 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.

II. Determine the toxicity of these regimens in these patients.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of alemtuzumab in these patients. II. Determine the immune response in patients treated with alemtuzumab. III. Determine changes in the number of CD52-positive cells in the blood and marrow of patients treated with alemtuzumab.

IV. 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.

  Eligibility

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

Inclusion Criteria:

  • 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
  • Performance status - Karnofsky 50-100% (for patients > 10 years of age)
  • Performance status - Lansky 50-100% (for patients ≤ 10 years of age)
  • At least 8 weeks
  • ALT ≤ 5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
  • Creatinine normal for age
  • Pulse oximetry > 94%
  • No evidence of dyspnea at rest
  • No exercise intolerance
  • No serious uncontrolled infection
  • No autoimmune hemolytic anemia
  • No autoimmune thrombocytopenia
  • 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)
  • 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
  • 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
  • Prior steroid therapy allowed
  • More than 2 weeks since prior radiotherapy and recovered
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
COG Phase I Consortium
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Anne Angiolillo COG Phase I Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00089349     History of Changes
Obsolete Identifiers: NCT00229606
Other Study ID Numbers: NCI-2012-01814, ADVL0222, CDR0000378240, NCI-05-C-0248, COG-ADVL0222, U01CA097452
Study First Received: August 4, 2004
Last Updated: June 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Methotrexate
Alemtuzumab
Antibodies
Antibodies, Monoclonal
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Dermatologic Agents
Folic Acid Antagonists

ClinicalTrials.gov processed this record on July 31, 2014