Subcutaneous Alemtuzumab (CAMPATH®, MabCampath®) in Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia

NCT00328198 | Completed Phase 2 Results DMC

• 2 other identifiers: CAM2032005-005074-69
• Study Type: interventional
• Target: 86
• Locations: 6 countries
• Sites: 21

Brief Summary

This is a Phase II, open-label, prospective, multicenter study to evaluate the efficacy and safety of subcutaneously administered alemtuzumab (CAMPATH, MabCampath) as therapy for patients with relapsed or refractory B-CLL who have been previously treated.

Conditions

B-Cell Chronic Lymphocytic Leukemia (B-CLL)

Keywords

CAMPATH; Alemtuzumab; Leukemia; MabCampath; Chronic; Subcutaneous; CLL; C-CLL; Relapsed; Refractory; Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Best Disease Response as Determined by the Independent Response Review Panel (IRRP)

  Participants were evaluated by the IRRP according to National Cancer Institute (NCI) 1996 response criteria. The best response observed during the study is summarized. Response categories include Complete Response (CR) with normal physical exam, marrow cells and blood values, Partial Response (PR) with a \>= 50% decrease from baseline in lymphocytes, lymphadenopathy and liver or spleen exam, Stable Disease (SD) without significant progression from baseline, or Progressive Disease (PD) with increased size/number of nodes, size of liver or spleen, increase in lymphocytes, aggressive histology.

  up to 44 weeks

• Percentage of Participants Who Had an Overall Response (OR) as Determined by the Independent Response Review Panel (IRRP)

  Participants were evaluated by the IRRP according to National Cancer Institute (NCI) 1996 response criteria. The percentage of participants whose best response observed during the study was either a Complete Response (CR) or a Partial Response (PR). Overall Response (OR) = CR + PR. A Complete Response (CR) exhibits a normal physical exam, marrow cells and blood values. A Partial Response (PR) has a \>= 50% decrease from baseline in lymphocytes, lymphadenopathy and liver or spleen exam.

  up to 44 weeks

Secondary Outcomes (5)

• Kaplan-Meier Estimates of Progression Free Survival as Determined by the Independent Response Review Panel (IRRP)

  up to 5 years

• Kaplan-Meier Estimates of Duration of Response as Determined by the Independent Response Review Panel (IRRP)

  up to 5 years

• Kaplan-Meier Estimates of Overall Survival

  up to 5 years

• Participants With a Minimal Residual Disease (MRD) Status of Negative

  44 weeks

• Participants With Treatment-Emergent Adverse Events (TEAE)

  up to 18 weeks of treatment plus 45 days

Study Arms (2)

Dose escalation

EXPERIMENTAL

Alemtuzumab is administered using escalating doses and alternating injection sites. The dose is escalated as tolerated using 3mg, 10mg, and 30mg administered subcutaneously (SC) (if tolerated).

Biological: Alemtuzumab

No escalation

EXPERIMENTAL

Alemtuzumab treatment is started immediately at the 30mg dose (with no escalation period), administered subcutaneously at alternating injection sites 3 times per week for up to 18 weeks.

Biological: Alemtuzumab

Interventions

Alemtuzumab BIOLOGICAL

Alemtuzumab is administered using escalating doses and alternating injection sites. The dose is escalated as tolerated using 3mg, 10mg, and 30mg administered subcutaneously (SC) (if tolerated). When escalation to 30 mg is tolerated, all subsequent doses are administered at 30 mg SC 3 times per week at alternating injection sites for up to 18 weeks. Part 1 of the study: The first 20 patients will be randomized to either Arm 1 (dose escalation) or Arm 2 (no escalation). Part 1 of the study has been completed; no additional patients will be enrolled in Part 1. An assigned review panel has reviewed the safety data from Part 1 and determined that all patients will be enrolled and treated under a no escalation schedule for Part 2 of the study.

Also known as: Campath®, MabCampath®

Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of B-cell chronic lymphocytic leukemia (B-CLL); according to the National Cancer Institute Working Group (NCI WG) Criteria.
• World Health Organization (WHO) performance status of 0, 1, or 2.
• Life expectancy ≥ 12 weeks.
• Previous therapy with at least one but no more than 5 regimens (single agent or combination regimen). One therapy regimen is defined as consecutive, contiguous cycles of the same drug(s) with no treatment interruptions lasting \> 3 months.
• Patient requires treatment for CLL per the following criteria: -Rai stage III or IV; -Rai stage 0-II with at least one of the following - evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia; Massive (i.e. greater than 6 cm below the left costal margin) or progressive splenomegaly; Progressive lymphocytosis with an increase of greater than 50% over a 2-month period or an anticipated doubling time of less than 6 months; Lymphocyte count \> 100\*10\^9/L; B symptoms.
• More than 3 weeks since prior chemotherapy. Patient must have recovered from the acute side effects incurred as a result of previous therapy.
• More than 3 weeks since using investigational agents. Patient must have recovered from the acute side effects incurred as a result of previous therapy.
• Serum creatinine and conjugated (direct) bilirubin less than or equal to 2 times the institutional upper limit of normal (ULN) unless secondary to direct infiltration of the liver with CLL.
• Female patients with childbearing potential must have a negative pregnancy test (serum or urine) within 2 weeks of first dose of study drug(s). All patients must agree to use an effective contraceptive method while on study treatment, if appropriate, and for a minimum of 6 months following study therapy.
• Signed, written informed consent (in the US, includes The Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization)

You may not qualify if:

• Positive Coombs test and evidence of active hemolysis.
• Platelet count less than 50\*10\^9/L without splenomegaly.
• History of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanized monoclonal antibodies.
• Previously treated with CAMPATH.
• Previous bone marrow transplant.
• Known central nervous system (CNS) involvement with B-CLL
• Active infection, including human immunodeficiency virus (HIV) positive.
• Active second malignancy.
• Recent documented history (within 2 years) of active tuberculosis (TB), current active TB infection, currently receiving anti-tuberculous medication (e.g., INH, rifampin, streptomycin, pyrazinamide, or others).
• Active hepatitis or a history of prior viral hepatitis B or hepatitis C, or positive hepatitis B serologies. Patients with a positive hepatitis B surface antibody (HBsAb) test with a documented history of prior hepatitis B immunization are eligible as long as other criteria are met (i.e. negative tests for: hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) and hepatitis C virus antibody (HCVAb)).
• Other severe, concurrent diseases (e.g., cardiac or pulmonary disease), mental disorders, or major organ malfunction (liver, kidney) that could interfere with the patient ability to participate in the study.
• Pregnant or nursing women.
• Cytomegalovirus (CMV) positive by polymerase chain reaction (PCR) (above the level of detection). A patient that is PCR positive will require treatment to reduce the viral load to a non-detectable level; but such a patient may be considered for study entry once the infection has been treated.
• Medical condition requiring chronic use of oral corticosteroids at a dose higher than physiologic replacement.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead
• Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma: collaborator

Study Sites (21)

Moores Cancer Center

La Jolla, California, 92093-0820, United States

Location

Wilshire Oncology Medical Group

La Verne, California, 91750, United States

Location

University of Colorado Cancer Center at University of Colorado Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Centers

Colorado Springs, Colorado, 80909, United States

Location

North Mississippi Hematology & Oncology Associates, Ltd.

Tupelo, Mississippi, 38801, United States

Location

Mid Ohio Oncology Hematology, Inc.

Columbus, Ohio, 43213, United States

Location

Joe Arrington Cancer Center

Lubbock, Texas, 79140, United States

Location

Academisch Ziekenhuis der Vrije Universiteit Brussel

Brussels, 1090, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, B-9000, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, B-3000, Belgium

Location

University Hospital Brno

Brno, 625 00, Czechia

Location

University Hospital Hradec Kralove (UH HK)

Hradec Králové, Czechia

Location

Hopital Hotel-Dieu

Clermont-Ferrand, 63058, France

Location

Hopital Claude Huriez

Lille, 59037, France

Location

Hopital Hotel-Dieu, CHU de Nantes-Service d'Hematologie Clinique

Nantes, France

Location

Institute of Hematology, Clinical Centre of Serbia

Belgrade, 11 000, Serbia

Location

Clinic of Hematology, Clinical Centre Vojvodina Novi Sad

Novi Sad, 21000, Serbia

Location

Leeds General Infirmary

Leeds, LS1 3EX, United Kingdom

Location

Royal Liverpool and Broadgreen Hospitals

Liverpool, L7 8XP, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia; Bronchiolitis Obliterans Syndrome; Recurrence

Interventions

Alemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Genzyme Medical Information
• Organization: Genzyme Corporation

1-800-745-4447

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2006
• First Posted: May 19, 2006
• Study Start: May 1, 2006
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: March 13, 2014
• Results First Posted: August 10, 2012

Record last verified: 2014-02

Locations

FR (3); US (7); GB (3); SE (2); CZ (2); BE (4)