Fludarabine (Fludara®) Plus Alemtuzumab (CAMPATH®, MabCampath®) vs Fludarabine Alone in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients

NCT00086580 | Completed Phase 3 Results DMC

• 2 other identifiers: CAM3142004-000149-39
• Study Type: interventional
• Target: 335
• Locations: 15 countries
• Sites: 48

Brief Summary

This is a Phase 3, prospective, multicenter, open-label, randomized, controlled study to evaluate and compare the efficacy and safety of fludarabine plus alemtuzumab versus fludarabine alone as second-line therapy for patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). Patients who meet all eligibility criteria and sign the informed consent document may be entered on the study.

Conditions

B-Cell Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) Assessment

  Progression-free survival was defined as the number of days from the date of randomization to the date of first objective documentation of progressive disease (PD) as determined by the treatment-blinded IRRP, or death due to any cause. Results are expressed in months.

  Up to 6 years

Secondary Outcomes (15)

• Participant Best Response to Treatment Assessed by the Independent Response Review Panel (IRRP)

  Up to 9 months

• Kaplan-Meier Estimates of Overall Survival Time

  Up to 6 years

• Kaplan Meier Estimates for Time to Disease Progression Assessed by the Independent Response Review Panel (IRRP)

  Up to 6 years

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

  Up to 6 years

• Kaplan-Meier Estimates for Time to Alternative Therapy

  Up to 6 years

Other Outcomes (4)

• Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) for Participants With Rai Stage I-II

  Up to 6 years

• Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) for Participants With Rai Stage III-IV

  Up to 6 years

• Kaplan-Meier Estimates of Overall Survival Time for Participants With Rai Stage I-II

  Up to 6 years

Study Arms (2)

Combination Arm (FluCAM)

EXPERIMENTAL

Biological: FluCAM [Fludara + Campath]

Fludarabine Alone

ACTIVE COMPARATOR

Biological: fludarabine phosphate

Interventions

FluCAM [Fludara + Campath] BIOLOGICAL

Phase A: Escalating Doses of alemtuzumab (Campath) Alone Day 1: alemtuzumab 3 mg intravenously (IV) over 2 hours. Day 2: alemtuzumab 10 mg IV over 2 hours if 3 mg was tolerated, else repeat 3 mg daily until tolerated. Day 3: alemtuzumab 30 mg IV over 2 hours if 10 mg was tolerated, else repeat 10 mg daily until tolerated. Participants were allowed 3-14 days to escalate to 30 mg. Once 30 mg was tolerated, the participant had to begin Phase B within 7 days. Phase B: FluCAM Cycle 1: Days 1,2,3 fludarabine phosphate administered at 30 mg/m\^2 over 30 minutes IV, followed within 1 hour by alemtuzumab 30 mg IV over 2 hours. A similar schedule is set for Cycles 2 through 6; duration of alemtuzumab infusions vary from 2-6 hours. Each 28-day period is 1 cycle. Fludarabine phosphate dosage is based on participants' body surface area at the beginning of each cycle. FluCAM administered up to a maximum of 6 cycles, based upon participants' response to therapy and toxicity.

Also known as: alemtuzumab, fludarabine phosphate, Fludara, Campath

Combination Arm (FluCAM)

fludarabine phosphate BIOLOGICAL

Fludarabine phosphate (Fludara) is administered at a dose of 25 mg/m\^2 IV over 15 to 30 minutes daily for 5 consecutive days (days 1 through 5) every 28 days (per package instructions). Each 28-day period is 1 cycle. The dose of fludarabine phosphate will be based on the participant's body surface area as calculated at the beginning of each cycle. Participants treated with fludarabine phosphate up to a maximum of 6 cycles, based upon their response to therapy and toxicity.

Also known as: Fludara

Fludarabine Alone

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.
• Relapsed or refractory disease after 1 prior regimen except patients who were refractory to (i.e., progressed on) fludarabine or alemtuzumab therapy. Patients who previously responded (complete response or partial response) to fludarabine or alemtuzumab therapy, but who have relapsed at the time of study entry, may be eligible but response to fludarabine or alemtuzumab therapy must have lasted \>12 months (i.e., \>12 months from a documented response to a documented relapse).
• Binet stage A, stage B, or stage C or Rai Stage I through IV disease with evidence of progression as evidenced by the presence of one or more of the following:
• I. Evidence of progressive marrow failure as manifested by: 1) a decrease in hemoglobin to \<11g/dL, or 2) a decrease in platelet count to \<100 x 10\^9/L within the previous 6 months, or 3) a decrease in absolute neutrophil count (ANC) to \<1.0 X 10\^9/L.
• II. Progressive splenomegaly to \>2 cm below the left costal margin or other organomegaly.
• III. Progressive lymphadenopathy.
• IV. Progressive lymphocytosis with an increase of 50% over a 2-month period, or an anticipated doubling time of less than 6 months.
• World Health Organization (WHO) performance status (PS) of 0 or 1.
• Life expectancy \>12 weeks.
• Anti-cancer therapy, major surgery, or irradiation was completed \>3 weeks before randomization in this study. Patient must have recovered from the acute side effects incurred as a result of previous therapy.
• Serum creatinine less than or equal to 2.0 x institutional upper limits of normal (ULN) and calculated creatinine clearance (CrCl) greater than or equal to 30mL/min using the Cockroft and Gault formula.
• Adequate liver function as indicated by a total bilirubin, AST, and ALT less than or equal to 2 x the institutional ULN value, unless directly attributable to the patient's tumor.
• Female patients with childbearing potential must have a negative serum pregnancy test with 2 weeks of first dose of study drug(s). Male and female 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.

You may not qualify if:

• Previously treated with \>1 prior regimen for B-CLL.
• Previously treated with a fludarabine plus alemtuzumab (FluCAM) regimen for B-CLL.
• Positive Coombs test and actively hemolyzing.
• Absolute neutrophil count (ANC) \<1.5 x 10\^9/L or platelet count \<75 x 10\^9/L, unless due to bone marrow involvement.
• Medical condition requiring chronic use of pharmacologic doses of oral corticosteroids, i.e. anything other than replacement dose levels.
• History of anaphylaxis following exposure to monoclonal antibodies.
• Use of investigational agents within 6 weeks prior to study randomization.
• Active infection or history of severe infection (grade 4) within 3 months prior to study randomization.
• Known to be human immunodeficiency virus (HIV) positive.
• Autoimmune thrombocytopenia.
• Active second malignancy.
• Known central nervous system (CNS) involvement with B-CLL.
• Other severe, concurrent diseases, including tuberculosis, mental disorders, serious cardiac functional capacity (Class III or IV as defined by the New York Heart Association Classification), severe diabetes, severe hypertension, pulmonary disease (chronic obstructive pulmonary disease \[COPD\] with hypoxemia), or major organ malfunction (liver, kidney) that could interfere with the patient's ability to participate in the study.
• Pregnant or nursing women.
• Patients that have progressed with more aggressive B-cell cancers such as Richter's syndrome.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (48)

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

Medizinische Universitatsklinik Graz

Graz, 8036, Austria

Location

Universitat Wien AKH, Innere Medizin I

Vienna, 1090, Austria

Location

University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski

Pleven, 5800, Bulgaria

Location

UMHAT St. Georgi, Hematology Clinic

Plovdiv, 4000, Bulgaria

Location

Multiprofile Hospital for Active Treatment "Alexandrovska"

Sofia, 1431, Bulgaria

Location

National Center for Heamtology and Transfusiology

Sofia, 1756, Bulgaria

Location

Multiprofile Hospital for Active Treatment, St. Marina

Varna, 9010, Bulgaria

Location

Cancer Care Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Hopital Notre-Dame du CHUM

Montreal, Quebec, H2L 4M1, Canada

Location

Clinical Hospital Center Rijeka, Department of Haematology

Rijeka, 51000, Croatia

Location

Clinical Hospital Merkur

Zagreb, 10000, Croatia

Location

University Hospital Dubrava

Zagreb, 10000, Croatia

Location

CHRU - Hopital Claude Huriez

Lille, 59037, France

Location

Charite-Universitatsmedizin Berlin Campus Benjamin-Franklin

Berlin, 12203, Germany

Location

Charite Universitatsklinikum der Humboldt-Universitat zu Berlin

Berlin, 13353, Germany

Location

Klinikum der Universitat zu Koln, Klinik 1 fur Innere Medizin

Cologne, 50924, Germany

Location

Robert-Bosch Krankenhaus GmbH

Stuttgart, 70376, Germany

Location

"Laikon" General Hospital, University of Athens

Goudi, Athens, 11527, Greece

Location

U.O. Oncologia Medica Azienda Ospedaliera "Pugliese-Ciaccio"

Cantanzaro, 88100, Italy

Location

Unita Operativa di Medicina Generale Reumatologia e Oncoematologia

Milan, 20132, Italy

Location

Istituto di Ematologia Dipartmento di Biotechnologie Celluari ed Ematologia, Universita di Roma "La Sapienza"

Rome, 00161, Italy

Location

Klinika Hematologii i Transplantacji Szpiku

Katowice, 40-027, Poland

Location

Klinika Hematologii AM

Lodz, 93-513, Poland

Location

Klinika Hematologii Pomorskiej Akademii Medycznej w Szczecinie

Szczecin, 71-252, Poland

Location

Katedra i Klinika Hamatologii, Onkologii I Chorob Wewnetrznych AM

Warsaw, 02-097, Poland

Location

Klinika Hematologii, Nowotworow Krwii 1 Transplantacji Szpiku

Wroclaw, 50-367, Poland

Location

Hospital de Santa Maria Servico de Hematologia Clinica/Hospital de dia de Hematologia

Lisbon, 1649-035, Portugal

Location

Hospital de Sao Teotonio, Servico de Hematologia/Hosptial de Dia Oncologico

Viseu, 3504-509, Portugal

Location

Institutol Clinic Fundeni, Clinica Heamtologie

Bucharest, 022328, Romania

Location

GU "Main Military Clinical Hospital named after acad. N.N.Burdenko of MO of Russia", Haematology Centre 3

Moscow, 105229, Russia

Location

GOUVPO "Saint-Petersburg State Medical University named after acad I.P.Pavlov of Roszdrav", Bone Marrow Transplantology Clinic

Saint Petersburg, 197089, Russia

Location

Saint-Petersburg GUZ "City Hospital #31" 3, Dynamo Prospect

Saint Petersburg, 197110, Russia

Location

State Healthcare Department "Sverdlovsk Regional Clinical Hospital #1",

Yekaterinburg, 620102, Russia

Location

University Hospital, Dept. of Hematology

Lund, 221 85, Sweden

Location

Orebro University Hospital, Dep. of Medicine

Örebro, 701 85, Sweden

Location

Universitetssjukhuset

Örebro, 701 85, Sweden

Location

Medicin kliniken/Hematologsektionen

Sundsvall, 851 86, Sweden

Location

Akademiska sjukhuset

Uppsala, 751 85, Sweden

Location

Cherkasskly Oncology Dispensary

Cherkasy, 79044, Ukraine

Location

City Clinical Hospital #4, Regional Hematology Center

Dnipro, 49102, Ukraine

Location

Donetsk State Medical University

Donetsk, 83045, Ukraine

Location

Kharkov Regional Clinical Oncology Center, Department of Hematology

Kharkiv, 61070, Ukraine

Location

Khmelnitskiy Regional Hospital, Hematology Department

Khmelnitskiy, 29000, Ukraine

Location

Institute of Oncology AMS of Ukraine

Kiev, 03022, Ukraine

Location

Institute of Hematology and Transfusiology AMS of Ukraine, City Clinical Hospital #9

Kiev, 04112, Ukraine

Location

Scientific Centre for Radiation Medicine AMS of Ukraine, Dept of Hematology and Transplantology

Kyiv, 03115, Ukraine

Location

Lviv National Medical University named Danilo Galytcky

Lviv, 79044, Ukraine

Location

Related Publications (4)

• Engert A, et al. Overall Survival Advantage and Acceptable Safety Profile with Fludarabine in Combination with Alemtuzumab (FluCam) in Previously Treated Patients with Advanced Stage Chronic Lymphocytic Leukemia. Poster Presentation at American Society of Hematology 10 December 2010; Blood (ASH Annual Meeting Abstracts), Nov 2010;116:919. http://ash.confex.com/ash/2010/webprogram/Paper31687.html

  RESULT

• Engert A, et al. Improved Progression-free Survival (PFS) of Alemtuzumab (Campath®, MabCampath®) plus Fludarabine (Fludara®) versus Fludarabine Alone as Second-line Treatment of Patients with B-Cell Chronic Lymphocytic Leukemia: Preliminary Results from a Phase III Randomized Trial. 51st ASH Annual Meeting. Blood 2009;114. Abstract 537. http://ash.confex.com/ash/2009/webprogram/Paper21929.html

  RESULT

• Engert A, et al. Fludarabine (FLU) plus Alemtuzumab (FluCAM) Improves Progression Free Survival versus Fludarabine in Previously Treated Chronic Lymphocytic Leukemia and Demonstrates Activity in High Risk Patients. Poster Presentation at European Hematology Association 12 June 2010. Abstract 0768. http://www.eventure-online.com/eventure/publicAbstractView.do?id=136964&congressId=3446

  RESULT

• Elter T, Gercheva-Kyuchukova L, Pylylpenko H, Robak T, Jaksic B, Rekhtman G, Kyrcz-Krzemien S, Vatutin M, Wu J, Sirard C, Hallek M, Engert A. Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukaemia: a randomised phase 3 trial. Lancet Oncol. 2011 Dec;12(13):1204-13. doi: 10.1016/S1470-2045(11)70242-X. Epub 2011 Oct 10.

  PMID: 21992852 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

fludarabine phosphate; Alemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; 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

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

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2004
• First Posted: July 8, 2004
• Study Start: July 1, 2004
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: March 13, 2014
• Results First Posted: August 11, 2011

Record last verified: 2014-02

Locations

IT (3); PT (2); US (1); FR (1); RO (1); CR (3); DE (4); AU (2); BU (5); CA (2); RU (4); UA (9); PL (5); SE (5); GR (1)