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

April 14, 2015 updated by: National Cancer Institute (NCI)

A Phase II Study of MOAD (Methotrexate, Vincristine, L-asparaginase and Dexamethasone) With Subcutaneous Campath for Adults With Relapsed or Refractory Acute Leukemia (ALL)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Aurora, Illinois, United States, 60504
        • Rush - Copley Medical Center
      • Chicago, Illinois, United States, 60616
        • Mercy Hospital and Medical Center
      • Joliet, Illinois, United States, 60435
        • Joliet Oncology-Hematology Associates Limited
      • Skokie, Illinois, United States, 60076
        • Edward H Kaplan MD and Associates
      • Urbana, Illinois, United States, 61801
        • Carle Clinic-Urbana Main
    • Indiana
      • Michigan City, Indiana, United States, 46360
        • Saint Anthony Memorial Health Center
    • Iowa
      • Sioux City, Iowa, United States, 51104
        • Saint Luke's Regional Medical Center
      • Sioux City, Iowa, United States, 51101
        • Siouxland Hematology Oncology Associates
      • Sioux City, Iowa, United States, 51104
        • Mercy Medical Center-Sioux City
    • Kansas
      • Chanute, Kansas, United States, 66720
        • Cancer Center of Kansas - Chanute
      • Dodge City, Kansas, United States, 67801
        • Cancer Center of Kansas - Dodge City
      • El Dorado, Kansas, United States, 67042
        • Cancer Center of Kansas - El Dorado
      • Fort Scott, Kansas, United States, 66701
        • Cancer Center of Kansas - Fort Scott
      • Independence, Kansas, United States, 67301
        • Cancer Center of Kansas-Independence
      • Kingman, Kansas, United States, 67068
        • Cancer Center of Kansas-Kingman
      • Lawrence, Kansas, United States, 66044
        • Lawrence Memorial Hospital
      • Liberal, Kansas, United States, 67901
        • Cancer Center of Kansas-Liberal
      • Newton, Kansas, United States, 67114
        • Cancer Center of Kansas - Newton
      • Parsons, Kansas, United States, 67357
        • Cancer Center of Kansas - Parsons
      • Pratt, Kansas, United States, 67124
        • Cancer Center of Kansas - Pratt
      • Salina, Kansas, United States, 67401
        • Cancer Center of Kansas - Salina
      • Wellington, Kansas, United States, 67152
        • Cancer Center of Kansas - Wellington
      • Wichita, Kansas, United States, 67208
        • Cancer Center of Kansas-Wichita Medical Arts Tower
      • Wichita, Kansas, United States, 67208
        • Associates In Womens Health
      • Wichita, Kansas, United States, 67214
        • Cancer Center of Kansas - Main Office
      • Wichita, Kansas, United States, 67214
        • Via Christi Regional Medical Center
      • Wichita, Kansas, United States, 67214
        • Wesley Medical Center
      • Wichita, Kansas, United States, 67214
        • Wichita CCOP
      • Winfield, Kansas, United States, 67156
        • Cancer Center of Kansas - Winfield
    • Minnesota
      • Burnsville, Minnesota, United States, 55337
        • Fairview Ridges Hospital
      • Coon Rapids, Minnesota, United States, 55433
        • Mercy Hospital
      • Edina, Minnesota, United States, 55435
        • Fairview-Southdale Hospital
      • Fridley, Minnesota, United States, 55432
        • Unity Hospital
      • Hutchinson, Minnesota, United States, 55350
        • Hutchinson Area Health Care
      • Maplewood, Minnesota, United States, 55109
        • Saint John's Hospital - Healtheast
      • Maplewood, Minnesota, United States, 55109
        • Minnesota Oncology Hematology PA-Maplewood
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Medical Center
      • Minneapolis, Minnesota, United States, 55407
        • Abbott-Northwestern Hospital
      • Robbinsdale, Minnesota, United States, 55422
        • North Memorial Medical Health Center
      • Saint Louis Park, Minnesota, United States, 55416
        • Park Nicollet Clinic - Saint Louis Park
      • Saint Louis Park, Minnesota, United States, 55416
        • Metro-Minnesota CCOP
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital
      • Saint Paul, Minnesota, United States, 55102
        • United Hospital
      • Shakopee, Minnesota, United States, 55379
        • Saint Francis Regional Medical Center
      • Stillwater, Minnesota, United States, 55082
        • Lakeview Hospital
      • Waconia, Minnesota, United States, 55387
        • Ridgeview Medical Center
      • Willmar, Minnesota, United States, 56201
        • Rice Memorial Hospital
      • Woodbury, Minnesota, United States, 55125
        • Minnesota Oncology and Hematology PA-Woodbury
    • New York
      • Bronx, New York, United States, 10467-2490
        • Montefiore Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822-2001
        • Geisinger Medical Center
      • Hazleton, Pennsylvania, United States, 18201
        • Geisinger Medical Center-Cancer Center Hazelton
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Milton S Hershey Medical Center
      • Lewistown, Pennsylvania, United States, 17044
        • Lewistown Hospital
      • State College, Pennsylvania, United States, 16801
        • Geisinger Medical Group
      • State College, Pennsylvania, United States, 16803
        • Mount Nittany Medical Center
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Geisinger Wyoming Valley
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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

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.
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time from registration to death from any cause. Patients alive were censored at follow up.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Peter Wiernik, Montefiore Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

February 1, 2013

Study Registration Dates

First Submitted

December 6, 2005

First Submitted That Met QC Criteria

December 6, 2005

First Posted (Estimate)

December 7, 2005

Study Record Updates

Last Update Posted (Estimate)

May 5, 2015

Last Update Submitted That Met QC Criteria

April 14, 2015

Last Verified

October 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00518
  • U10CA021115 (U.S. NIH Grant/Contract)
  • E1904 (Other Identifier: Eastern Cooperative Oncology Group)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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