Chronic lymphocytic leukemia (CLL) is a malignant disease. CLL is the most common form of leukemia in western countries. Median age at diagnosis is 70 years, and only 10-15% of patients are younger than 50 years. Despite some therapeutic progress, standard treatment is not curative for CLL MedDRA version: 12.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia
Conditions
Interventions
Trade Name: Rituximab
Product Name: Rituximab
Product Code: EU/1/98/067/001
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Other descriptive name: ant
Sponsors
FRED HUTCHINSON CANCER RESEARCH CENTER
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with a diagnosis of CLL (or small lymphocytic lymphoma) or Diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL. 2. Patients with B-Cell CLL or PLL who: a. Failed to meet NCI Working Group criteria2 (Appendix I) for complete or partial response after therapy with regimens containing fludarabine (or another nucleoside analog, e.g. 2-CDA, pentostatin) or with disease relapse within 12 months after completing therapy with fludarabine (or another nucleoside analog) containing regimen. b. Failed FCR or PCR combination chemotherapy at any time point. c. Patients with novo or acquired “17p deletion” cytogenetic abnormality. Patients should have received induction chemotherapy but could be transplanted in 1st CR. 3. Patients who have suitable HLA-matched related or unrelated donors willing to receive G-CSF, undergo leukopharesis to collect PBMC, and to donate stem cells Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Infection with HIV. 2. Active diagnosis of CNS involvement with CLL. For LP requirement, see Appendix O. 3. Patients unwilling to use contraceptive techniques before and for 12 months after HCT 4. Pregnant women or females who are breastfeeding. 5. The addition of cytotoxic agents for “cytoreduction” with the exception of tyrosine kinase inhibitors (such as imatinib mesylate), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning. 6. Active bacterial or fungal infections unresponsive to medical therapy. 7. Performance status: a. Karnofsky score 50 years or there is a history of prior transplant, anthracycline exposure or history of cardiac disease. ii. Poorly controlled hypertension despite multiple antihypertensives. b. Pulmonary: i. DLCO 3 mg/dl, or symptomatic biliary disease. 9. Patients with active non-hematologic malignancies (except non-melanoma skin cancers). 10. Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a >20% risk of disease recurrence
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: 1. Estimate the overall response rate (CR + PR) by standard morphologic, flow cytometric, and molecular techniques. 2. Assess the rate of relapse/progression. 3. Define incidences of RRT and infections within the first 200 days and the incidence of TRM within the first year. 4. Estimate incidences of grade II-III and III-IV acute GVHD and chronic GVHD. 5. Assess the impacts of Rituximab 6. Graft-versus-leukemia analysis ;Primary end point(s): The primary objective of this protocol is to estimate survival using allogeneic HCT from related or unrelated donors after nonmyeloablative conditioning and peri-transplant Rituximab in patients with advanced CLL, and to gain a preliminary indication as to whether survival is improved compared to treatment with conventional salvage therapies. The primary endpoint will be survival at 18 months. The 18 months time point is chosen because prior experience with HCT indicates that survival reaches a relative plateau by that time, and thus offers an endpoint that can be evaluated somewhat more rapidly than 2 year survival. The estimated 18 months survival with standard treatment (Campath-1H) from historical patients is approximately 0.45. This treatment approach will be deemed promising for further study if we can achieve reasonable confidence that survival exceeds 0.45. Reasonable confidence will be taken to mean that the lower limit of a one-sided 80% confidence interval for the true survival fraction at 18 months is greater than 0.45.;Main Objective: 1. Determine whether nonmyeloablative conditioning and allogeneic HCT improves survival at 18 months for patients with fludarabine-refractory, FCR-failed, or del 17p CLL over that of historical controls (45% at 18 months) given CAMPATH-1H.[14] | — |
Countries
Denmark
Outcome results
None listed