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Combination Chemotherapy and Alemtuzumab in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

This study has been terminated.
(slow accrual)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00262925
First received: December 6, 2005
Last updated: April 25, 2014
Last verified: October 2013
  Purpose

This phase II trial is studying how well giving combination chemotherapy together with alemtuzumab works in treating patients with relapsed or refractory acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving combination chemotherapy together with alemtuzumab may kill more cancer cells.


Condition Intervention Phase
Recurrent Adult Acute Lymphoblastic Leukemia
Biological: alemtuzumab
Drug: asparaginase
Drug: methotrexate
Drug: dexamethasone
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: vincristine
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 MOAD (Methotrexate, Vincristine, L-asparaginase and Dexamethasone) With Subcutaneous Campath for Adults With Relapsed or Refractory Acute Leukemia (ALL)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Complete Response Rate [ Time Frame: assessed before the first consolidation cycle and first cytoreduction cycle, before the first and after the last maintenance cycle; after discontinuing treatment, assessed every 3 months if < 2 years and every 6 months if 2-5 years from study entry ] [ Designated as safety issue: No ]

    Complete response requires that all of the following be present for at least four weeks.

    1. Peripheral Blood Counts: Neutrophil count >= 1.0 x 109/L, Platelet count >= 100 x 109/L, Reduced hemoglobin concentration or hematocrit has no bearing on remission status, Leukemic blasts must not be present in the peripheral blood.

    2 .Bone Marrow Aspirate and Biopsy: Cellularity of bone marrow biopsy must be > 20% with maturation of all cell lines, <= 5% blasts.

    3. Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present.



Secondary Outcome Measures:
  • Overall Survival [ Time Frame: assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry ] [ Designated as safety issue: No ]
    Time from registration to death from any cause. Patients alive were censored at follow up.


Enrollment: 12
Study Start Date: June 2006
Study Completion Date: February 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, enzyme inhibitor therapy)

INDUCTION THERAPY: Patients receive methotrexate IV; vincristine IV and asparaginase IM ; oral dexamethasone ; and alemtuzumab SC.

CONSOLIDATION THERAPY: Patients receive methotrexate IV and asparaginase IM.

CYTOREDUCTION THERAPY: Patients receive vincristine IV and methotrexate IV; leucovorin calcium IV; and oral dexamethasone.

MAINTENANCE THERAPY: Patients receive oral mercaptopurine; oral methotrexate; vincristine IV; and oral dexamethasone.

Biological: alemtuzumab
Given subcutaneously
Other Names:
  • anti-CD52 monoclonal antibody
  • Campath-1H
  • MoAb CD52
  • Monoclonal Antibody Campath-1H
  • Monoclonal Antibody CD52
Drug: asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: methotrexate
Given IV or orally
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: dexamethasone
Given orally
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: mercaptopurine
Given orally
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: vincristine
Given IV
Other Names:
  • vincristine sulfate
  • leurocristine sulfate
  • VCR
  • Vincasar PFS

Detailed Description:

OBJECTIVES:

I. Determine the complete response rate in patients with relapsed or refractory acute lymphoblastic leukemia treated with methotrexate, vincristine, asparaginase, and dexamethasone (MOAB) in combination with alemtuzumab.

II. Determine disease-free and/or overall survival of patients treated with this regimen.

III. Determine the toxic effects of this regimen in these patients.

IV. Correlate the density of cluster of differentiation 52 (CD52) molecules on the surface of leukemic lymphoblasts with response in patients treated with this regimen.

V. Correlate the presence of minimal residual disease at the time of maximal response to this regimen with overall outcome in these patients.

OUTLINE: This is a multicenter study. The study had two steps. Step 1: 5 mg dose of Campath (alemtuzumab); Step 2: 10 mg dose of Campath.

INDUCTION THERAPY: Patients receive methotrexate intravenously (IV) on day 1; vincristine IV and asparaginase intramuscularly (IM) on day 2; oral dexamethasone on days 1-10; and alemtuzumab subcutaneously (SC) on days 1, 4, and 7. Treatment repeats every 10 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete remission (CR) proceed to consolidation therapy.

CONSOLIDATION THERAPY: Patients receive methotrexate IV on day 1 and asparaginase IM on day 2. Treatment repeats every 10 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who remain in CR proceed to cytoreduction therapy.

CYTOREDUCTION THERAPY: Patients receive vincristine IV and methotrexate IV over 6 hours on day 1; leucovorin calcium IV continuously over 24 hours on days 1 and 2 and then orally 4 times a day on day 3; and oral dexamethasone on days 2-6. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients who remain in CR proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive oral mercaptopurine on days 1-30; oral methotrexate on days 1, 8, 15, and 22; vincristine IV on day 1; and oral dexamethasone on days 1-5. Treatment repeats every 30 days for 36 courses in the absence of disease progression or unacceptable toxicity.

Patients are assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry.

PROJECTED ACCRUAL: Allowing for two dose levels, a maximum of 48 patients may be accrued approximately in 30 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Refractory or relapsed acute lymphoblastic leukemia

    • Must be in first relapse or have failed to achieve complete remission with 1 prior regimen
  • Prior central nervous system (CNS) leukemia allowed provided cerebrospinal fluid is normal
  • ECOG Performance status of 0-3
  • Bilirubin normal
  • Creatinine normal
  • Human immunodeficiency virus (HIV) negative
  • Negative pregnancy test
  • Fertile patients must use effective contraception

Exclusion criteria:

  • Hepatitis B positivity
  • Bacterial or fungal infection
  • Infection requiring treatment with antibiotics
  • Active cytomegalovirus infection by molecular detection methods
  • Known hypersensitivity to alemtuzumab or its components
  • Pregnant or nursing
  • Other malignancy within the past 5 years except adequately treated basal cell skin cancer or cervical carcinoma
  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: NCT00262925

  Show 58 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Peter Wiernik Montefiore Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00262925     History of Changes
Other Study ID Numbers: NCI-2009-00518, E1904, U10CA021115
Study First Received: December 6, 2005
Results First Received: April 25, 2014
Last Updated: April 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
MOAD
Methotrexate
Vincristine
L-asparaginase
Dexamethasone
Subcutaneous Campath

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
6-Mercaptopurine
Alemtuzumab
Antibodies
Antibodies, Monoclonal
Asparaginase
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Levoleucovorin
Methotrexate
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Inflammatory Agents
Antidotes
Antiemetics
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on November 20, 2014