A Study of MabThera/Rituxan (Rituximab) in Combination With Fludarabine And Cyclophosphamide as Primary Therapy in Elderly Patients With Chronic Lymphocytic Leukemia

NCT01263704 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ML25464
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 12

Brief Summary

This single arm, open-label study will assess the safety and efficacy of low dose fludarabine and cyclophosphamide in combination with standard dose MabThera/Rituxan (rituximab) as primary therapy in elderly patients (\>/= 65 years) with chronic lymphocytic leukemia. Patients will receive six 28-day cycles of treatment with Mabthera/Rituxan (375 mg/m2 intravenously \[iv\] Day 0 of cycle 1, 500 mg/m2 iv Day 1 of cycles 2-6), fludarabine (12.5 mg/m2/d iv Days 1-3, cycles 1-6) and cyclophosphamide (150 mg/m2/d iv Days 1-3, cycles 1-6). Anticipated time on study treatment is 6 months, with a 30-month follow-up period.

Conditions

Lymphocytic Leukemia, Chronic

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) according to National Cancer Institute - Working Group \[NCI-WG\] guidelines. CR: no clonal B lymphocytes in peripheral blood, no significant lymphadenopathy, liver and spleen normal size, no disease symptoms, blood counts: absolute neutrophil count (ANC) \>1,500/microliter (mcL), platelets \> 100,000/mcL, hemoglobin \> 11.0 grams/deciliter (g/dL), normocellular bone marrow. PR: \>/= 50% decrease in clonal B lymphocyte count, \>/= 50% reduction in lymphadenopathy, \>/= 50% reduction of liver or spleen enlargement and ANC \>1,500/mcL, platelets \> 100,000/mcL, hemoglobin \> 11.0 g/dL OR \>/= 50% increase in ANC, platelets or hemoglobin.

  Up to 42 months

Secondary Outcomes (5)

• Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to 53 months

• Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations

  Up to 53 months

• Hospitalization Days

  Up to 53 months

• Progression-free Survival (PFS)

  Up to 53 months

• Quality of Life (QoL): Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire

  [Visit 1 (Screening, Week 0), at Visits 11 (Week 45) and 14 (Week 80) and at the end of the study (Month 42)]

Study Arms (1)

Rituximab plus Fludarabine and Cyclophosphamide

EXPERIMENTAL

Elderly participants with chronic lymphocytic leukemia (CLL) will receive combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment is followed by a follow up period of 36 months.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab

Interventions

Cyclophosphamide DRUG

150 milligrams per square meter (mg/m\^2) intravenously (IV) on Days 1-3 of each 28-day cycle for 6 cycles

Rituximab plus Fludarabine and Cyclophosphamide

Fludarabine DRUG

12.5 mg/m\^2 IV on Days 1-3 of every 28-day cycle for 6 cycles

Rituximab plus Fludarabine and Cyclophosphamide

Rituximab DRUG

375 mg/m\^2 IV Day 0 of Cycle 1, 500 mg/m\^2 IV Day 1 of Cycles 2-6. Each cycle was 28 days.

Also known as: MabThera/Rituxan

Rituximab plus Fludarabine and Cyclophosphamide

Eligibility Criteria

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

You may qualify if:

• Adult patients, \>/= 65 years of age
• Previously untreated B-cell chronic lymphocytic leukemia (CLL)
• Binet stage C or active Binet stage A and B disease

You may not qualify if:

• Prior treatment for CLL
• CLL with transformation (Richter's syndrome)
• Suspected or known central nervous system (CNS) involvement of CLL
• Impaired renal or hepatic function
• Human Immunodeficiency Virus (HIV) positivity, active hepatitis B/C or Hepatitis B Virus (HBV) surface antigen positive, or any active or uncontrolled infections
• Patients with anti-HBV core antibodies (past infection with HBV) but who are negative for Hepatitis B Virus Surface Antigen (HBVsAg) (either anti-HBS Ab positive or negative) and are positive for HBV- Deoxyribonucleic acid (DNA) by Polymerase chain reaction (PCR) analysis
• Concomitant diseases requiring chronic steroid administration
• Active second malignancy within the 2 years prior to study (except for non-melanoma skin cancer and in situ cervix or breast or prostate carcinoma)
• Eastern Cooperative Oncology Group (ECOG) performance status \>/= 3

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (12)

Haemek Medical Center; Hematology Department

Afula, 18101, Israel

Location

Soroka Medical Center; Hematology Deptartment

Beersheba, 8410101, Israel

Location

Rambam Medical Center; Heamatology & Bone Marrow Transplantation

Haifa, 3109601, Israel

Location

Bnei-Zion Medical Center; Hematology Dept

Haifa, 3339419, Israel

Location

Shaare Zedek Medical Center; Hematology Dept.

Jerusalem, 9103102, Israel

Location

Hadassah Ein Karem Hospital; Haematology

Jerusalem, 9112001, Israel

Location

Meir Medical Center; Internal Dept A

Kfar Saba, 44281, Israel

Location

Western Galilee Hospital - Nahariya

Nahariya, 22100, Israel

Location

Beilinson Medical Center; Haematology

Petah Tikva, 49100, Israel

Location

Kaplan Medical Center

Rehovot, 7661041, Israel

Location

ASSAF Harofe; Department of Hematology

Rishon LeZiyyon, 70300, Israel

Location

Ichilov Sourasky Medical Center; Heamatology

Tel Aviv, 6423906, Israel

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Cyclophosphamide; fludarabine; Rituximab

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: December 17, 2010
• First Posted: December 21, 2010
• Study Start: July 17, 2011
• Primary Completion: April 3, 2017
• Study Completion: April 3, 2017
• Last Updated: April 23, 2018
• Results First Posted: April 23, 2018

Record last verified: 2018-04

Locations

IL (12)