A Phase 3 interventional study of Cladribine and Cyclophosphamide in Lymphocytic Leukemia, Chronic, sponsored by Hoffmann-La Roche. Completed at 6 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-08-20.
Sponsored by Hoffmann-La Roche · Phase 3, Interventional, and Treatment
This study will assess the effect of maintenance treatment with rituximab in comparison with observation period (no treatment), in participants with progressive B-cell CLL who have had previous first-line induction treatment with rituximab, cladribine and cyclophosphamide (RCC regimen). After 6 months of RCC induction therapy, participants will be randomized either to receive maintenance treatment with rituximab or to receive no treatment (observation only) for 96 weeks. Participants completing maintenance/observation period will be followed-up for approximately 3 years.
1,648 studies on the registry are indexed under Leukemia, Lymphocytic, Chronic, B-Cell; 245 are open to participants now.
This study's enrollment of 128 is above the median of 40 across 1,356 interventional studies indexed under Leukemia, Lymphocytic, Chronic, B-Cell.
Browse Leukemia, Lymphocytic, Chronic, B-Cell studies →Hoffmann-La Roche is the lead sponsor of 2,099 studies on the registry; 88 are open to participants now.
Of its 324 completed or terminated interventional studies of FDA-regulated products, 245 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Participants will receive rituximab at a dose of 375 milligrams per meter squared (mg/m\^2) as intravenous (IV) infusion on Day 1, cladribine at a dose of 0.12 milligrams per kilogram per day (mg/kg/day) as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 will be administered in Cycles 2-6. Each cycle will be of 28 days in duration.
Drug: Cladribine · Drug: Cyclophosphamide · Drug: Rituximab
Participants with PR or CR after induction phase who will be randomized to maintenance arm will receive rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants will receive rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).
Drug: Rituximab
Participants with PR or CR after induction phase who will be randomized to observation arm will not receive any intervention. Participants will be assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.
Cladribine will be adminiatered at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4 of each 28-day cycle during induction phase.
Cyclophosphamide will be administred at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 of each 28-day cycle during induction phase.
Rituximab will be administered at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 during induction phase. Rituximab will be administered at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle during maintenance phase.
Also known as: MabThera
Percentage of Participants With Disease Progression (PD), Relapse, or Death Due to Any Cause Assessed According to the National Cancer Institute (NCI) Revised Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia (CLL)
PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (greater than \[\>\]1.5 centimeters \[cm\]), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of greater than or equal to (\>/=) 50 percent (%) in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by \>/=50%; an increase in the number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000 per microliter (/mcL); transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.
Time frame: From randomization to PD, Relapse, or death due to any cause (overall approximately 5 years)
Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL
PFS was defined as the time from date of randomization to date of PD, relapse, or death due to any cause. Participants alive with no evidence of PD or relapse were censored at date of last clinical examination. PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (\>1.5 cm), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of \>/=50% in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by \>/=50%; an increase in the number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000/mcL; transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.
Time frame: From randomization to PD, relapse, or death due to any cause (overall approximately 5 years)
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL
CR was achieved if participants met all of the following criteria \>/= 2 months after last treatment: no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, platelets (PL) \>100,000/mcL, hemoglobin (Hb) \>11.0 grams per deciliter (g/dL), bone marrow (BM) sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly (decrease in lymph node size by \>/=50% compared to pre-treatment state, no increase in any lymph node, no new enlarged lymph node); a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline).
Time frame: 8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129)
Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR
MRD was defined by the presence of tumor cells in bone marrow, using 4-color flow cytometry of cluster of differentiation (CD)19/CD5/CD20/CD79b. MRD was assessed in participants who achieved CR or PR. CR: if participants met all of the following criteria \>/=2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline).
Time frame: 8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129)
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors
PFS: time from date of randomization to date of PD, relapse, or death from any cause. Participants alive with no evidence of PD or relapse were censored at date of last clinical examination. PD: appearance of any new lesion, such as enlarged lymph nodes (\>1.5 cm), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of \>/=50% in greatest determined diameter of any previous site; an increase in previously noted enlargement of liver or spleen by \>/=50%; an increase in number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000/mcL; transformation to a more aggressive histology; or occurrence of cytopenia attributable to CLL. Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed relationship between clinical markers and clinical outcome (PFS) after study treatment.
Time frame: From randomization to PD, relapse, or death due to any cause (overall approximately 5 years)
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29
CR was achieved if participants met all of the following criteria \>/= 2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed the relationship between clinical markers and clinical outcome (response) after study treatment.
Time frame: 8 weeks after the last dose of rituximab during induction treatment (Week 29)
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129
CR was achieved if participants met all of the following criteria \>/=2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed the relationship between clinical markers and clinical outcome (response) after study treatment.
Time frame: 12 weeks after the end of maintenance treatment or observation phase (Week 129)
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29
MRD: the presence of tumor cells in bone marrow, using 4-color flow cytometry of CD19/CD5/CD20/CD79b. MRD was assessed in participants who achieved CR or PR. CR (\>/=2 months after last treatment): no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed relationship between clinical markers and MRD after study treatment.
Time frame: 8 weeks after the last dose of rituximab during induction treatment (Week 29)
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129
MRD: the presence of tumor cells in bone marrow, using 4-color flow cytometry of CD19/CD5/CD20/CD79b. MRD was assessed in participants who achieved CR or PR. CR (\>/=2 months after last treatment): no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed relationship between clinical markers and MRD after study treatment.
Time frame: 12 weeks after the end of maintenance treatment or observation phase (Week 129)
| Milestone | Induction: Rituximab, Cladribine, Cyclophosphamide | Maintenance Arm: Rituximab | Observation Arm: No Intervention |
|---|---|---|---|
| Started | 128 | 0 | 0 |
| Completed | 66 | 0 | 0 |
| Not completed | 62 | 0 | 0 |
| Withdrew: Disease progression | 1 | 0 | 0 |
| Withdrew: Eligibility criteria violation | 2 | 0 | 0 |
| Withdrew: Early termination - no additional info | 59 | 0 | 0 |
| Milestone | Induction: Rituximab, Cladribine, Cyclophosphamide | Maintenance Arm: Rituximab | Observation Arm: No Intervention |
|---|---|---|---|
| Started | 0 | 33 | 33 |
| Completed | 0 | 5 | 3 |
| Not completed | 0 | 28 | 30 |
| Withdrew: Early termination - no additional info | 0 | 15 | 8 |
| Withdrew: Death | 0 | 1 | 2 |
| Withdrew: Lost to follow-up | 0 | 4 | 4 |
| Withdrew: Progression | 0 | 5 | 14 |
| Withdrew: Relapse | 0 | 3 | 2 |
PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (greater than \[\>\]1.5 centimeters \[cm\]), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of greater than or equal to (\>/=) 50 percent (%) in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by \>/=50%; an increase in the number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000 per microliter (/mcL); transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.
| percentage of participants | Maintenance Arm: Rituximab | Observation Arm: No Intervention | All Randomized Participants |
|---|---|---|---|
| Percentage of Participants With Disease Progression (PD), Relapse, or Death Due to Any Cause Assessed According to the National Cancer Institute (NCI) Revised Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia (CLL) | 27.3 | 54.5 | 40.9 |
PFS was defined as the time from date of randomization to date of PD, relapse, or death due to any cause. Participants alive with no evidence of PD or relapse were censored at date of last clinical examination. PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (\>1.5 cm), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of \>/=50% in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by \>/=50%; an increase in the number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000/mcL; transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.
| years | Maintenance Arm: Rituximab | Observation Arm: No Intervention | All Randomized Participants |
|---|---|---|---|
| Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL | NA (3.0 to NA) | 2.1 (1.9 to NA) | 3.1 (2.2 to NA) |
CR was achieved if participants met all of the following criteria \>/= 2 months after last treatment: no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, platelets (PL) \>100,000/mcL, hemoglobin (Hb) \>11.0 grams per deciliter (g/dL), bone marrow (BM) sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly (decrease in lymph node size by \>/=50% compared to pre-treatment state, no increase in any lymph node, no new enlarged lymph node); a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline).
| percentage of participants | Maintenance Arm: Rituximab | Observation Arm: No Intervention | Overall Population |
|---|---|---|---|
| Week 29 | — | — | 73.2 (64.9 to 82.1) |
| Week 129 | 90.5 (85.7 to 100.0) | 72.2 (55.6 to 92.9) | 82.1 (71.8 to 93.5) |
MRD was defined by the presence of tumor cells in bone marrow, using 4-color flow cytometry of cluster of differentiation (CD)19/CD5/CD20/CD79b. MRD was assessed in participants who achieved CR or PR. CR: if participants met all of the following criteria \>/=2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline).
| percentage of participants | Maintenance Arm: Rituximab | Observation Arm: No Intervention | All Randomized Participants |
|---|---|---|---|
| Week 29 | — | — | 15.4 (7.7 to 23.7) |
| Week 129 | 28.6 (14.3 to 55.6) | 20.0 (10.0 to 48.7) | 25.0 (12.5 to 43.9) |
PFS: time from date of randomization to date of PD, relapse, or death from any cause. Participants alive with no evidence of PD or relapse were censored at date of last clinical examination. PD: appearance of any new lesion, such as enlarged lymph nodes (\>1.5 cm), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of \>/=50% in greatest determined diameter of any previous site; an increase in previously noted enlargement of liver or spleen by \>/=50%; an increase in number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000/mcL; transformation to a more aggressive histology; or occurrence of cytopenia attributable to CLL. Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed relationship between clinical markers and clinical outcome (PFS) after study treatment.
| years | All Randomized Participants |
|---|---|
| Age <60 years | 3.0 (2.2 to NA) |
| Age >/=60 years | 4.0 (1.9 to NA) |
| Sex: Female | 4.0 (2.2 to NA) |
| Sex: Male | 3.0 (2.1 to NA) |
| Rai Stage: I or II | 3.1 (2.1 to NA) |
| Rai Stage: III or IV | 3.0 (2.1 to NA) |
| Beta-2-Microglobulin >/= Median Value | 1.9 (1.4 to NA) |
| Beta-2-Microglobulin <Median Value | NA (3.5 to NA) |
| Zeta-Associated Protein (ZAP)-70: Negative | 3.0 (2.1 to NA) |
| ZAP-70 Expression: Positive | NA (4.0 to NA) |
| CD38 Expression: Negative | 2.1 (1.9 to NA) |
| CD38 Expression: Positive | 2.8 (1.9 to NA) |
| Cytogenetic abnormality 17p: No | 3.1 (2.2 to NA) |
| Cytogenetic abnormality 17p: Yes | 1.9 (1.9 to NA) |
| Cytogenetic abnormality 13q: No | 3.5 (1.4 to NA) |
| Cytogenetic abnormality 13q: Yes | 3.0 (1.9 to NA) |
| Cytogenetic abnormality 11q: No | 3.5 (2.1 to NA) |
| Cytogenetic abnormality 11q: Yes | 2.8 (1.9 to NA) |
| Cytogenetic abnormality 12q: No | 2.2 (1.9 to NA) |
| Cytogenetic abnormality 12q: Yes | 3.1 (3.1 to NA) |
CR was achieved if participants met all of the following criteria \>/= 2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed the relationship between clinical markers and clinical outcome (response) after study treatment.
| percentage of participants | Overall Population |
|---|---|
| Age <60 years | 73.3 |
| Age >/=60 years | 73.0 |
| Sex: Female | 80.6 |
| Sex: Male | 69.7 |
| Rai Stage: I or II | 77.5 |
| Rai Stage: III or IV | 61.5 |
| Beta-2-Microglobulin >/= Median Value | 64.6 |
| Beta-2-Microglobulin <Median Value | 83.0 |
| ZAP-70 Expression: Negative | 67.1 |
| ZAP-70 Expression: Positive | 94.7 |
| CD38 Expression: Negative | 73.1 |
| CD38 Expression: Positive | 71.4 |
| Cytogenetic abnormality 17p: No | 72.8 |
| Cytogenetic abnormality 17p: Yes | 71.4 |
| Cytogenetic abnormality 13q: No | 62.9 |
| Cytogenetic abnormality 13q: Yes | 76.1 |
| Cytogenetic abnormality 11q: No | 69.5 |
| Cytogenetic abnormality 11q: Yes | 79.2 |
| Cytogenetic abnormality 12q: No | 67.6 |
| Cytogenetic abnormality 12q: Yes | 66.7 |
CR was achieved if participants met all of the following criteria \>/=2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed the relationship between clinical markers and clinical outcome (response) after study treatment.
| percentage of participants | All Randomized Participants |
|---|---|
| Age <60 years | 80.8 |
| Age >/=60 years | 84.6 |
| Sex: Female | 85.7 |
| Sex: Male | 80.0 |
| Rai Stage: I or II | 80.6 |
| Rai Stage: III or IV | 87.5 |
| Beta-2-Microglobulin >/= Median Value | 76.9 |
| Beta-2-Microglobulin <Median Value | 84.0 |
| ZAP-70 Expression: Negative | 83.3 |
| ZAP-70 Expression: Positive | 83.3 |
| CD38 Expression: Negative | 77.8 |
| CD38 Expression: Positive | 75.0 |
| Cytogenetic abnormality 17p: No | 86.7 |
| Cytogenetic abnormality 17p: Yes | 50.0 |
| Cytogenetic abnormality 13q: No | 90.0 |
| Cytogenetic abnormality 13q: Yes | 76.5 |
| Cytogenetic abnormality 11q: No | 84.2 |
| Cytogenetic abnormality 11q: Yes | 80.0 |
| Cytogenetic abnormality 12q: No | 76.2 |
| Cytogenetic abnormality 12q: Yes | 100.0 |
MRD: the presence of tumor cells in bone marrow, using 4-color flow cytometry of CD19/CD5/CD20/CD79b. MRD was assessed in participants who achieved CR or PR. CR (\>/=2 months after last treatment): no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed relationship between clinical markers and MRD after study treatment.
| percentage of participants | All Randomized Participants |
|---|---|
| Age <60 years | 87.8 |
| Age >/=60 years | 79.2 |
| Sex: Female | 87.5 |
| Sex: Male | 82.9 |
| Rai Stage: I or II | 80.4 |
| Rai Stage: III or IV | 100.0 |
| Beta-2-Microglobulin >/= Median Value | 93.1 |
| Beta-2-Microglobulin <Median Value | 77.1 |
| ZAP-70 Expression: Negative | 82.6 |
| ZAP-70 Expression: Positive | 100.0 |
| CD38 Expression: Negative | 83.3 |
| CD38 Expression: Positive | 95.5 |
| Cytogenetic abnormality 17p: No | 83.6 |
| Cytogenetic abnormality 17p: Yes | 100.0 |
| Cytogenetic abnormality 13q: No | 84.2 |
| Cytogenetic abnormality 13q: Yes | 81.8 |
| Cytogenetic abnormality 11q: No | 83.3 |
| Cytogenetic abnormality 11q: Yes | 84.2 |
| Cytogenetic abnormality 12q: No | 80.5 |
| Cytogenetic abnormality 12q: Yes | 75.0 |
MRD: the presence of tumor cells in bone marrow, using 4-color flow cytometry of CD19/CD5/CD20/CD79b. MRD was assessed in participants who achieved CR or PR. CR (\>/=2 months after last treatment): no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils \>1500/mcL, PL \>100,000/mcL, Hb \>11.0 g/dL, BM sample must be normocellular for age with lymphocytes \<30% of nucleated cells. PR: a reduction in Ly; a reduction of \>/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils \>1500/mcL, PL \>100,000/mcL (or 50% improvement from baseline), Hb \>11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed relationship between clinical markers and MRD after study treatment.
| percentage of participants | All Randomized Participants |
|---|---|
| Age <60 years | 72.2 |
| Age >/=60 years | 83.3 |
| Sex: Female | 71.4 |
| Sex: Male | 76.5 |
| Rai Stage: I or II | 75.0 |
| Rai Stage: III or IV | 75.0 |
| Beta-2-Microglobulin >/= Median Value | 88.9 |
| Beta-2-Microglobulin <Median Value | 71.4 |
| ZAP-70 Expression: Negative | 66.7 |
| ZAP-70 Expression: Positive | 100.0 |
| CD38 Expression: Negative | 60.0 |
| CD38 Expression: Positive | 77.8 |
| Cytogenetic abnormality 17p: No | 76.2 |
| Cytogenetic abnormality 17p: Yes | 0.0 |
| Cytogenetic abnormality 13q: No | 75.0 |
| Cytogenetic abnormality 13q: Yes | 66.7 |
| Cytogenetic abnormality 11q: No | 66.7 |
| Cytogenetic abnormality 11q: Yes | 75.0 |
| Cytogenetic abnormality 12q: No | 66.7 |
| Cytogenetic abnormality 12q: Yes | 66.7 |
Collected over From Day 1 to end of study (up to 261 weeks). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Induction (Excluding Maintenance/ Observation) | — | 23/62 (37.1%) | 58/62 (93.5%) |
| Maintenance Arm: Rituximab | — | 13/33 (39.4%) | 31/33 (93.9%) |
| Observation Arm: No Intervention | — | 9/33 (27.3%) | 32/33 (97%) |
| All Participants | — | 45/128 (35.2%) | 121/128 (94.5%) |
| Event | Induction (Excluding Maintenance/ Observation) | Maintenance Arm: Rituximab | Observation Arm: No Intervention | All Participants |
|---|---|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 1/62 | 4/33 | 0/33 | 5/128 |
| Febrile neutropeniaBlood and lymphatic system disorders | 4/62 | 2/33 | 0/33 | 6/128 |
| LeukopeniaBlood and lymphatic system disorders | 0/62 | 1/33 | 2/33 | 3/128 |
| PneumoniaInfections and infestations | 1/62 | 1/33 | 2/33 | 4/128 |
| PancytopeniaBlood and lymphatic system disorders | 3/62 | 0/33 | 0/33 | 3/128 |
| AnaemiaBlood and lymphatic system disorders | 2/62 | 0/33 | 0/33 | 2/128 |
| Cytomegalovirus infectionInfections and infestations | 2/62 | 0/33 | 0/33 | 2/128 |
| Herpes zosterInfections and infestations | 2/62 | 0/33 | 1/33 | 3/128 |
| Abdominal pain upperGastrointestinal disorders | 0/62 | 1/33 | 0/33 | 1/128 |
| Disease progressionGeneral disorders | 0/62 | 0/33 | 1/33 | 1/128 |
| Event | Induction (Excluding Maintenance/ Observation) | Maintenance Arm: Rituximab | Observation Arm: No Intervention | All Participants |
|---|---|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 47/62 | 26/33 | 20/33 | 93/128 |
| NauseaGastrointestinal disorders | 7/62 | 12/33 | 4/33 | 23/128 |
| ThrombocytopeniaBlood and lymphatic system disorders | 18/62 | 5/33 | 5/33 | 28/128 |
| DiarrhoeaGastrointestinal disorders | 6/62 | 7/33 | 3/33 | 16/128 |
| LeukopeniaBlood and lymphatic system disorders | 1/62 | 6/33 | 6/33 | 13/128 |
| Upper respiratory tract infectionInfections and infestations | 4/62 | 3/33 | 6/33 | 13/128 |
| Pulmonary fibrosisRespiratory, thoracic and mediastinal disorders | 0/62 | 6/33 | 2/33 | 8/128 |
| AnaemiaBlood and lymphatic system disorders | 11/62 | 1/33 | 3/33 | 15/128 |
| PyrexiaGeneral disorders | 11/62 | 5/33 | 3/33 | 19/128 |
| LymphopeniaBlood and lymphatic system disorders | 0/62 | 3/33 | 5/33 | 8/128 |
All enrolled participants who received at least one dose of study medication.
| Age, Continuous(years) | Induction: Rituximab, Cladribine, Cyclophosphamide |
|---|---|
| Mean | 57.5 ± 8.3 |
| Sex: Female, Male(Participants) | Induction: Rituximab, Cladribine, Cyclophosphamide |
|---|---|
| Female | 44 |
| Male | 84 |
Ran from Jul 2009 to primary completion in Sep 2015, 73 months.
Results were first posted in Aug 2018, 2 years 11 months after primary completion.
Of 57 industry-sponsored phase 3 interventional studies under Leukemia, Lymphocytic, Chronic, B-Cell, half reached primary completion within 53 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 73. This study's 73 months is above that.
Counting every sponsor, half of 79 studies reached it within 59 months; a quarter within 43 and three quarters within 76.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Nov 2017. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Cladribine · Cyclophosphamide · Rituximab
Leukemia, Lymphocytic, Chronic, B-Cell →