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

Condition(s) targeted: Recurrent Adult Acute Lymphoblastic Leukemia

Intervention: alemtuzumab (Biological); asparaginase (Drug); methotrexate (Drug); dexamethasone (Drug); leucovorin calcium (Drug); mercaptopurine (Drug); vincristine (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Peter Wiernik, Principal Investigator, Affiliation: Montefiore Medical Center

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.

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)

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Complete Response Rate

Secondary outcome: Overall Survival

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Rush - Copley Medical Center, Aurora, Illinois 60504, United States

Mercy Hospital and Medical Center, Chicago, Illinois 60616, United States

Joliet Oncology-Hematology Associates Limited, Joliet, Illinois 60435, United States

Edward H Kaplan MD and Associates, Skokie, Illinois 60076, United States

Carle Clinic-Urbana Main, Urbana, Illinois 61801, United States

Saint Anthony Memorial Health Center, Michigan City, Indiana 46360, United States

Mercy Medical Center-Sioux City, Sioux City, Iowa 51104, United States

Saint Luke's Regional Medical Center, Sioux City, Iowa 51104, United States

Siouxland Hematology Oncology Associates, Sioux City, Iowa 51101, United States

Cancer Center of Kansas - Chanute, Chanute, Kansas 66720, United States

Cancer Center of Kansas - Dodge City, Dodge City, Kansas 67801, United States

Cancer Center of Kansas - El Dorado, El Dorado, Kansas 67042, United States

Cancer Center of Kansas - Fort Scott, Fort Scott, Kansas 66701, United States

Cancer Center of Kansas-Independence, Independence, Kansas 67301, United States

Cancer Center of Kansas-Kingman, Kingman, Kansas 67068, United States

Lawrence Memorial Hospital, Lawrence, Kansas 66044, United States

Cancer Center of Kansas-Liberal, Liberal, Kansas 67901, United States

Cancer Center of Kansas - Newton, Newton, Kansas 67114, United States

Cancer Center of Kansas - Parsons, Parsons, Kansas 67357, United States

Cancer Center of Kansas - Pratt, Pratt, Kansas 67124, United States

Cancer Center of Kansas - Salina, Salina, Kansas 67401, United States

Cancer Center of Kansas - Wellington, Wellington, Kansas 67152, United States

Associates In Womens Health, Wichita, Kansas 67208, United States

Cancer Center of Kansas - Main Office, Wichita, Kansas 67214, United States

Cancer Center of Kansas-Wichita Medical Arts Tower, Wichita, Kansas 67208, United States

Via Christi Regional Medical Center, Wichita, Kansas 67214, United States

Wesley Medical Center, Wichita, Kansas 67214, United States

Wichita CCOP, Wichita, Kansas 67214, United States

Cancer Center of Kansas - Winfield, Winfield, Kansas 67156, United States

Fairview Ridges Hospital, Burnsville, Minnesota 55337, United States

Mercy Hospital, Coon Rapids, Minnesota 55433, United States

Fairview-Southdale Hospital, Edina, Minnesota 55435, United States

Unity Hospital, Fridley, Minnesota 55432, United States

Hutchinson Area Health Care, Hutchinson, Minnesota 55350, United States

Minnesota Oncology Hematology PA-Maplewood, Maplewood, Minnesota 55109, United States

Saint John's Hospital - Healtheast, Maplewood, Minnesota 55109, United States

Abbott-Northwestern Hospital, Minneapolis, Minnesota 55407, United States

Hennepin County Medical Center, Minneapolis, Minnesota 55415, United States

North Memorial Medical Health Center, Robbinsdale, Minnesota 55422, United States

Metro-Minnesota CCOP, Saint Louis Park, Minnesota 55416, United States

Park Nicollet Clinic - Saint Louis Park, Saint Louis Park, Minnesota 55416, United States

Regions Hospital, Saint Paul, Minnesota 55101, United States

United Hospital, Saint Paul, Minnesota 55102, United States

Saint Francis Regional Medical Center, Shakopee, Minnesota 55379, United States

Lakeview Hospital, Stillwater, Minnesota 55082, United States

Ridgeview Medical Center, Waconia, Minnesota 55387, United States

Rice Memorial Hospital, Willmar, Minnesota 56201, United States

Minnesota Oncology and Hematology PA-Woodbury, Woodbury, Minnesota 55125, United States

Montefiore Medical Center, Bronx, New York 10467-2490, United States

Case Western Reserve University, Cleveland, Ohio 44106, United States

Geisinger Medical Center, Danville, Pennsylvania 17822-2001, United States

Geisinger Medical Center-Cancer Center Hazelton, Hazleton, Pennsylvania 18201, United States

Penn State Milton S Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States

Lewistown Hospital, Lewistown, Pennsylvania 17044, United States

Geisinger Medical Group, State College, Pennsylvania 16801, United States

Mount Nittany Medical Center, State College, Pennsylvania 16803, United States

Geisinger Wyoming Valley, Wilkes-Barre, Pennsylvania 18711, United States

University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792, United States

Starting date: June 2006
Last updated: April 14, 2015