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

Recurrent Adult Acute Lymphoblastic Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00262925
• Other study ID #: NCI-2009-00518
• Secondary ID: E1904U10CA021115
• Status: Terminated
• Phase: Phase 2
• First received: December 6, 2005
• Last updated: April 14, 2015
• Start date: June 2006
• Est. completion date: February 2013

Study information

• Verified date: October 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: February 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Adult Acute Lymphoblastic Leukemia

Intervention

Biological:
• alemtuzumab
Given subcutaneously

Drug:
• asparaginase
Given IM
• methotrexate
Given IV or orally
• dexamethasone
Given orally
• leucovorin calcium
Given IV
• mercaptopurine
Given orally
• vincristine
Given IV

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response Rate	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	No
Secondary	Overall Survival	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	No