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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00262925
First received: December 6, 2005
Last updated: October 25, 2013
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 tablet
Drug: vincristine sulfate
Other: laboratory biomarker analysis
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 for MOAD in combination with Campath in adult patients with relapsed or refractory ALL [ Time Frame: After 6 courses of induction treatment, assessed up to 5 years ] [ Designated as safety issue: No ]
    With this two-stage design, the probability of stopping at the end of the first stage is 0.60 if the true response rate is 50%, but is 0.04 if the true response rate is 75%; this design has a power of 92% and a one-sided type I error of 0.09. The response at another dose level of Campath will be described in technical report separately.

  • Disease-free survival [ Time Frame: From the date of documented complete remission to the date of first treatment failure (relapse or death before relapse), assessed up to 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From the date of registration to date of death, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: From baseline to up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
    All toxicities will be monitored closely using ECOG's standard AE mechanism. Dose-limiting toxicity (DLT) is defined as a treatment-related toxicity that happens in induction or consolidation and results in prolonged delay of two weeks or longer, including patients who discontinue therapy permanently due to treatment-related toxicity.

  • Association of CD52 expression levels with outcome [ Time Frame: From baseline to up to 5 years ] [ Designated as safety issue: No ]
    Levels of CD52 expression in terms of intensity of fluorescence staining will be compared between patients who achieve CR and patients who do not, using the Wilcoxon rank sum test. Effect size is defined as the difference in means of the two groups divided by the assumed common standard deviation of the two groups. This power calculation is based on the power of the t-test to detect the same effect size and the Pitman efficiency of the Wilcoxon rank sum test to the t-test being at least 0.864.

  • Correlation of the presence of minimal residual disease with overall outcome [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  • Minimal residual disease (MRD) levels by flow cytometry [ Time Frame: Day 1 of each course of consolidation therapy ] [ Designated as safety issue: No ]
    MRD levels will be retrospectively correlated with clinical response.


Enrollment: 85
Study Start Date: June 2006
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, enzyme inhibitor therapy)

Detailed Description Section

INDUCTION THERAPY: Patients receive methotrexate IV; vincristine IV and asparaginase IM; oral dexamethasone; and alemtuzumab SC on days 1, 4, and 7.

CONSOLIDATION THERAPY: Patients receive methotrexate IV and asparaginase IM.

CYTOREDUCTION THERAPY: Patients receive vincristine IV and oral 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 tablet
Given orally
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Other: laboratory biomarker analysis
Correlative studies

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 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.

INDUCTION THERAPY: Patients receive methotrexate IV on day 1; vincristine IV and asparaginase intramuscularly (IM) on day 2; oral dexamethasone on days 1-10; and alemtuzumab subcutaneously 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.

After completion of study treatment, patients are followed periodically for 5 years from the date of registration to this study.

  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 CNS leukemia allowed provided cerebrospinal fluid is normal
  • Performance status - ECOG 0-3
  • Bilirubin normal
  • No hepatitis B positivity
  • Creatinine normal
  • HIV negative
  • No bacterial or fungal infection
  • No infection requiring treatment with antibiotics
  • No active cytomegalovirus infection by molecular detection methods
  • No known hypersensitivity to alemtuzumab or its components
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except adequately treated basal cell skin cancer or cervical carcinoma
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00262925

  Show 58 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Peter Wiernik Eastern Cooperative Oncology Group
  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, NCI-2009-00518, CDR0000450765, ECOG-E1904, E1904, E1904, U10CA021115
Study First Received: December 6, 2005
Last Updated: October 25, 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
Campath 1G
Alemtuzumab
Asparaginase
Dexamethasone
Vincristine
BB 1101
Antibodies
Antibodies, Monoclonal
Antibodies, Neoplasm
Dexamethasone acetate
Dexamethasone 21-phosphate
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014