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

Phase 2

Terminated

Conditions: Recurrent Adult Acute Lymphoblastic Leukemia

Interventions: Biological: alemtuzumab
Drug: asparaginase
Drug: methotrexate
Drug: dexamethasone
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: vincristine

Registration Number: NCT00262925

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 12

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (chemotherapy, enzyme inhibitor therapy)	alemtuzumab	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.
Treatment (chemotherapy, enzyme inhibitor therapy)	leucovorin calcium	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.
Treatment (chemotherapy, enzyme inhibitor therapy)	methotrexate	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.
Treatment (chemotherapy, enzyme inhibitor therapy)	dexamethasone	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.
Treatment (chemotherapy, enzyme inhibitor therapy)	asparaginase	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.
Treatment (chemotherapy, enzyme inhibitor therapy)	mercaptopurine	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.
Treatment (chemotherapy, enzyme inhibitor therapy)	vincristine	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.

Primary Outcome Measures

Name	Time	Method
Complete Response Rate	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	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.

Trial Locations

Locations (58): Mercy Hospital and Medical Center
🇺🇸
Chicago, Illinois, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
Rush - Copley Medical Center
🇺🇸
Aurora, Illinois, United States
Joliet Oncology-Hematology Associates Limited
🇺🇸
Joliet, Illinois, United States
Edward H Kaplan MD and Associates
🇺🇸
Skokie, Illinois, United States
Carle Clinic-Urbana Main
🇺🇸
Urbana, Illinois, United States
Mercy Medical Center-Sioux City
🇺🇸
Sioux City, Iowa, United States
Saint Anthony Memorial Health Center
🇺🇸
Michigan City, Indiana, United States
Saint Luke's Regional Medical Center
🇺🇸
Sioux City, Iowa, United States
Cancer Center of Kansas - Dodge City
🇺🇸
Dodge City, Kansas, United States
Cancer Center of Kansas - Fort Scott
🇺🇸
Fort Scott, Kansas, United States
Via Christi Regional Medical Center
🇺🇸
Wichita, Kansas, United States
Wichita CCOP
🇺🇸
Wichita, Kansas, United States
Fairview Ridges Hospital
🇺🇸
Burnsville, Minnesota, United States
Mercy Hospital
🇺🇸
Coon Rapids, Minnesota, United States
Fairview-Southdale Hospital
🇺🇸
Edina, Minnesota, United States
Hutchinson Area Health Care
🇺🇸
Hutchinson, Minnesota, United States
Unity Hospital
🇺🇸
Fridley, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸
Maplewood, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸
Maplewood, Minnesota, United States
Metro-Minnesota CCOP
🇺🇸
Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸
Saint Paul, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸
Shakopee, Minnesota, United States
Ridgeview Medical Center
🇺🇸
Waconia, Minnesota, United States
Lakeview Hospital
🇺🇸
Stillwater, Minnesota, United States
Minnesota Oncology and Hematology PA-Woodbury
🇺🇸
Woodbury, Minnesota, United States
Rice Memorial Hospital
🇺🇸
Willmar, Minnesota, United States
Geisinger Medical Center-Cancer Center Hazelton
🇺🇸
Hazleton, Pennsylvania, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Lewistown Hospital
🇺🇸
Lewistown, Pennsylvania, United States
Penn State Milton S Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
Mount Nittany Medical Center
🇺🇸
State College, Pennsylvania, United States
Geisinger Wyoming Valley
🇺🇸
Wilkes-Barre, Pennsylvania, United States
Geisinger Medical Group
🇺🇸
State College, Pennsylvania, United States
Wesley Medical Center
🇺🇸
Wichita, Kansas, United States
Lawrence Memorial Hospital
🇺🇸
Lawrence, Kansas, United States
Cancer Center of Kansas - Pratt
🇺🇸
Pratt, Kansas, United States
Cancer Center of Kansas - Salina
🇺🇸
Salina, Kansas, United States
Cancer Center of Kansas-Independence
🇺🇸
Independence, Kansas, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas - Chanute
🇺🇸
Chanute, Kansas, United States
Cancer Center of Kansas - Main Office
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas - Newton
🇺🇸
Newton, Kansas, United States
Cancer Center of Kansas - Parsons
🇺🇸
Parsons, Kansas, United States
Cancer Center of Kansas - Wellington
🇺🇸
Wellington, Kansas, United States
Cancer Center of Kansas - Winfield
🇺🇸
Winfield, Kansas, United States
Cancer Center of Kansas-Kingman
🇺🇸
Kingman, Kansas, United States
Associates In Womens Health
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas - El Dorado
🇺🇸
El Dorado, Kansas, United States
Cancer Center of Kansas-Liberal
🇺🇸
Liberal, Kansas, United States
North Memorial Medical Health Center
🇺🇸
Robbinsdale, Minnesota, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Abbott-Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Siouxland Hematology Oncology Associates
🇺🇸
Sioux City, Iowa, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸
Saint Louis Park, Minnesota, United States
United Hospital
🇺🇸
Saint Paul, Minnesota, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States