Chronic Lymphocytic Leukemia
Conditions
Keywords
Chronic Lymphocytic Leukemia, CD-52 and CD-20 Positive, Refractory, Relapsed
Brief summary
The goal of this clinical research study is to learn if giving CAMPATH-1H with rituximab can shrink or slow the growth of the disease in patients with chronic lymphoid disorders that have either not responded or whose disease has returned after treatment with standard therapies.
Detailed description
Objectives: 1. To determine the efficacy and response rates of Campath-1H when given as a continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of chronic lymphoid disorders that are refractory to conventional therapy, have relapsed, or have no established frontline therapy. 2. To assess the safety of the combination of Campath-1H when given as a continuous intravenous infusion followed by subcutaneous injection plus rituximab in chronic lymphoid disorders that express both CD52 and CD20 cell surface antigens. 3. To measure levels of soluble (s) CD20 and sCD52 as well as levels of Campath-1H, rituximab and antibody complexes of rituximab/CD20 and Campath-1H/CD52 in patients with chronic lymphoid disorders treated with Campath-1H plus rituximab.
Interventions
DRUGCampath-1H
15 mg/day Continuous infusion by vein (IV) for 6 days then given twice a week for remaining three weeks as 30 mg injection under skin to complete one treatment course of 4 weeks.
DRUGRituximab
375 mg/m\^2 IV infusion on day 1, then 500 mg/m\^2 on days 8, 15, and 22.
Sponsors
Bayer
M.D. Anderson Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>/=15 years. 2. Written informed consent. 3. Patients with chronic lymphoid malignancies that are either refractory to frontline therapy or have relapsed and that have a predicted probability of response of less than 20% with conventional therapy or allogeneic/autologous stem cell transplantation. 4. The following histologies are included: B-cell chronic lymphocytic leukemia (B-CLL or B-cell CLL), B-cell prolymphocytic leukemia (PLL), chronic lymphoid leukemia (CLL/PLL), hairy cell leukemia and hairy cell variant, mantle cell leukemia/lymphoma, marginal zone lymphoma/leukemia, splenic lymphoma with villous lymphocytes, CLL with evidence of transformation (e.g., Richter's transformation), large granular lymphocytic leukemia (LGL and NK-cell type). 5. Patients with above mentioned histologies whose malignant cell population have expressed both CD52 and CD20 in \>/= 20% of cells as assessed by flow cytometry or immunohistochemistry. Expression of CD20 or CD52 \< 20% is permitted if patients received rituximab or alemtuzumab, respectively, within 3 months prior to study start.
Exclusion criteria
1. Patients who have previously received Rituximab and CAMPATH-1H in combination are excluded. 2. ECOG performance status of \</= 2. 3. Serum creatinine \</= 2mg/dL and total bilirubin of £ 2 mg/dL unless due to direct infiltration of the liver or kidney with malignant cells. 4. Patients with a past history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanized monoclonal antibodies are excluded \<CDR = complementarity determining regions\>. 5. Negative pregnancy test (serum or urine) if female and of childbearing potential only (non-childbearing is defined as greater than one year post-menopausal or surgically sterilized). 6. No prior chemotherapy, immunotherapy, or hormonal therapy within 2 weeks prior to study start. Hormonal replacement therapy is permitted. No prior therapy with monoclonal antibodies for at least 4 weeks prior to study start. 7. Patients at high risk of hepatitis B virus (HBV) infection and active HBV infection are excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response | After each 4 week course of treatment | Overall response categorized as 'Complete Remission,' 'Partial Remission,' or 'No Response.' Blood tests weekly while on active therapy, within 4-6 weeks following last dose of therapy, and every 3 to 6 (+/- month) thereafter as long as on study. Repeat bone marrow biopsy/aspirate with flow cytometry as applicable at the end of first course of therapy, (1 week) within 4-6 weeks following the last dose of therapy and every 6 to 12 months (+/-) thereafter as long as on study. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period 10/21/02 - 3/27/09; all patients were registered at the University of Texas MD Anderson Cancer Center.
Pre-assignment details
Of 48 patients enrolled, 41 patients were evaluable for response (2 patients withdrew before starting treatment and 2 were ineligible).
Participants by arm
| Arm | Count |
|---|---|
| Campath-1H + Rituximab Campath 15 mg/day continuous intravenous (IV) infusion for 6 days, then twice a week for 3 weeks as 30 mg injection under skin to complete 4 week treatment course.
Rituximab 375 mg/m\^2 IV infusion day 1, then 500 mg/m\^2 on days 8, 15 + 22. | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Campath-1H + Rituximab |
|---|---|
| Age Continuous | 59 years |
| Region of Enrollment United States | 44 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 44 |
| serious Total, serious adverse events | 8 / 44 |
Outcome results
Primary
Overall Response
Overall response categorized as 'Complete Remission,' 'Partial Remission,' or 'No Response.' Blood tests weekly while on active therapy, within 4-6 weeks following last dose of therapy, and every 3 to 6 (+/- month) thereafter as long as on study. Repeat bone marrow biopsy/aspirate with flow cytometry as applicable at the end of first course of therapy, (1 week) within 4-6 weeks following the last dose of therapy and every 6 to 12 months (+/-) thereafter as long as on study.
Time frame: After each 4 week course of treatment
Population: Analysis treated population 41 evaluable patients (44 treated, 3 not evaluable for response).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Campath-1H + Rituximab | Overall Response | Complete Remission | 8 Participants |
| Campath-1H + Rituximab | Overall Response | Partial Remission | 14 Participants |
| Campath-1H + Rituximab | Overall Response | No Response | 19 Participants |