Hairy Cell Leukemia
Conditions
Keywords
Hairy Cell Leukemia, Cladribine, Rituximab, Minimal Residual Disease, Leukemia
Brief summary
Background: Hairy cell leukemia (HCL) is highly responsive to but not curable by cladribine (CdA). HCL responds to rituximab, which is not yet standard therapy for HCL. Patients with the interleukin 2 (IL-2) receptor (CD25)-negative hairy cell leukemia variant (HCLv) respond poorly to initial cladribine but do respond to rituximab in anecdotal reports. Deoxycytidine kinase phosphorylates cladribine to chlorodeoxyadenosine triphosphate (CdATP), which incorporates into deoxyribonucleic acid (DNA), leading to DNA strand breaks and inhibition of DNA synthesis. Rituximab is an anti-cluster of differentiation 20 (CD20) monoclonal antibody which induces apoptosis and either complement or antibody dependent cytotoxicity (antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). Patients in complete remission (CR) to cladribine have minimal residual disease (MRD) by immunohistochemistry of the bone marrow biopsy (BMBx IHC), a risk for early relapse. Tests for HCL MRD in blood or marrow include flow cytometry fluorescence-activated cell sorting (FACS) or polymerase chain reaction (PCR) using consensus primers. The most sensitive HCL MRD test is real-time quantitative PCR using sequence-specific primers real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR). In studies with limited follow-up, MRD detected by tests other than RQ-PCR can be eliminated by rituximab after cladribine in greater than 90 percent of patients, but MRD rates after cladribine alone are unknown. Simultaneous cladribine and rituximab might be superior or inferior to delaying rituximab until detection of MRD. Only 4 HCL-specific trials are listed on Cancer.gov: a phase II trial of cladribine followed 4 weeks later by 8 weekly doses of rituximab, and phase I-II trials of recombinant immunotoxins targeting cluster of differentiation-22 (CD22) (BL22, HA22) and CD25 (LMB-2). Objectives: Primary: To determine if HCL MRD differs at 6 months after cladribine with or without rituximab administered concurrently with cladribine. Secondary: * To compare cladribine plus rituximab vs cladribine alone in terms of 1) initial MRD-free survival and disease-free survival, and 2) response to delayed rituximab for relapse, to determine if early rituximab compromises later response. * To determine if MRD levels and tumor markers (soluble CD25 and CD22) after cladribine and/or rituximab correlate with response and clinical endpoints. * To determine, using MRD and tumor marker data, when bone marrow biopsy (BMBx) can be avoided. * To compare response and MRD after the 1st and 2nd courses of cladribine. * To evaluate the effects of cladribine and rituximab on normal T- and B-cells. * To enhance the study of HCL biology by cloning, sequencing and characterizing monoclonal immunoglobulin rearrangements. Eligibility: HCL with 0-1 prior courses of cladribine and treatment indicated. Design: Cladribine 0.15 mg/Kg/day times 5 doses each by 2hour(hr) intravenous (i.v.) infusion (days 1-5) Rituximab 375 mg/m\^2/week times 8 weeks, randomized half to begin day 1, then repeat for all patients with blood-MRD relapse at least 6 months after cladribine. Also, may repeat for those with blood-MRD relapse at least 6 months after delayed rituximab. MRD tests used for the primary objective will be limited to BMBx IHC, blood FACS or blood consensus PCR, all Clinical Laboratory Improvement Amendments (CLIA) certified. Blood MRD relapse is defined as FACS positivity or low blood counts (ANC less than 1500/microl, platelet (Plt) less than 100,000/microl, or hemoglobin (Hgb) less than 11). Stratification: 68 patients with 0 and 62 with 1 prior course of cladribine. Statistics: 80% power to discriminate rates of MRD of 5 vs 25%, or 10 vs 35% Non-randomized arm: 20 with HCLv will begin rituximab with cladribine. Accrual Ceiling: 152 patients (130 HCL, 2 extra HCL if needed, and 20 HCLv.)
Detailed description
Background: Hairy cell leukemia (HCL) is highly responsive to but not curable by cladribine (CdA). HCL responds to rituximab, which is not yet standard therapy for HCL. Patients with the interleukin 2 (IL-2) receptor (CD25)-negative hairy cell leukemia variant (HCLv) respond poorly to initial cladribine but do respond to rituximab in anecdotal reports. Purine analogs cladribine and pentostatin have similar efficacy for HCL, both inhibiting deoxyribonucleic acid (DNA) synthesis selectively in HCL cells. Cladribine is effective after just 1 cycle. Rituximab is an anti-cluster of differentiation 20 (CD20) monoclonal antibody which induces apoptosis and either complement or antibody dependent cytotoxicity (antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). Patients in complete remission (CR) to cladribine have minimal residual disease (MRD) by immunohistochemistry of the bone marrow biopsy (BMBx IHC), a risk for early relapse. Tests for HCL MRD in blood or marrow include flow cytometry fluorescence-activated cell sorting (FACS) or polymerase chain reaction (PCR) using consensus primers. The most sensitive HCL MRD test is real-time quantitative PCR using sequence-specific primers real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR). In studies with limited follow-up, MRD detected by tests other than RQ-PCR can be eliminated by rituximab after cladribine in \> 90% of patients, but MRD rates after purine analog alone are unknown. Simultaneous cladribine and rituximab might be superior or inferior to delaying rituximab until detection of MRD. Only 4 HCL-specific trials are listed on Cancer.gov: a phase II trial of cladribine followed 4 weeks later by 8 weekly doses of rituximab, and phase I-II trials of recombinant immunotoxins targeting cluster of differentiation-22 (CD22) (BL22, HA22) and CD25 (LMB-2). Objective: To determine if HCL MRD differs at 6 months after cladribine with or without rituximab administered concurrently with cladribine. Eligibility: HCL with 0-1 prior courses of cladribine or pentostatin and treatment indicated. Design: Cladribine 0.15 mg/Kg/day times 5 doses each by 2hour(hr) intravenous (i.v.) infusion (days 1-5) Rituximab 375 mg/m\^2/week times 8 weeks, randomized half to begin day 1, then repeat for all patients with blood-MRD relapse at least 6 months after cladribine. Also, may repeat for those with blood-MRD relapse at least 6 months after delayed rituximab. MRD tests used for the primary objective will be limited to BMBx IHC, blood FACS, and bone marrow aspirate FACS, all Clinical Laboratory Improvement Amendments (CLIA) certified. Blood MRD relapse is defined as FACS positivity or low blood counts (absolute neutrophil count (ANC) less than 1500/microl, platelet (Plt) less than 100,000/microl, or hemoglobin (Hgb) less than 11) attributed to HCL. Patients FACS-negative in both blood and bone marrow aspirate are considered MRD-negative complete response (CR) regardless of blood counts. Randomization: 68 HCL patients with 0 and 62 with 1 prior course of purine analog Statistics: 80% power to discriminate rates of MRD of 5 vs. 25%, or 10 vs. 35% Non-randomized HCLv arm: 20 patients with HCLv will begin rituximab with cladribine. Non-randomized HCL arm: 25 newly diagnosed patients will be enrolled to receive rituximab beginning day 1, but beginning before the 1st dose of cladribine, rather than after. Accrual ceiling: 175 evaluable patients (155 HCL and 20 HCLv)
Interventions
DIAGNOSTIC_TESTEKG
Baseline and week 5.
DIAGNOSTIC_TESTEchocardiogram
Baseline.
DIAGNOSTIC_TESTAbdominal/splenic ultrasound
Baseline and week 5.
PROCEDUREStress test
Baseline.
DRUGCladribine
Cladribine 0.15 mg/Kg/day by 2-hour intravenous (i.v.) infusion days 1-5. The infusion time may be changed to 1 hour at the discretion of the principal investigator (PI).
DRUGRituximab
Rituximab 375 mg/m\^2 intravenous (i.v.) infusion every week x8, begin day 1 in half of randomized patients and in all hairy cell leukemia variant (HCLv) patients, and then again in all patients at least 6 months later when hairy cell leukemia (HCL) is detected by blood fluorescence-activated cell sorting (FACS).
PROCEDUREBMbx
Baseline and week 5.
DIAGNOSTIC_TESTMRI
Baseline and week 5.
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: Evidence of Hairy Cell Leukemia (HCL) by flow cytometry, reviewed by the Laboratory of Pathology, National Cancer Institute (NCI), including positivity for Cluster of Differentiation 19 (CD19), Cluster of Differentiation 22 (CD22), cluster of differentiation 20 (CD20), and integrin alpha X (CD11c). Bone marrow biopsy (BMBx) consistent with HCL, reviewed by Laboratory of Pathology, NCI. BMBx may be negative in hairy cell leukemia variant, (HCLv) in patients with increasing peripheral blood HCLv cells and spleen size. Treatment indicated based on demonstration of at least one of the following, no more than 4 weeks from the time of enrollment, and no less than 6 months after prior purine analog and no less than 4 weeks after other prior treatment, if applicable. * Neutropenia (absolute neutrophil count (ANC) less than 1000 cells/microl). * Anemia (hemoglobin (Hgb) less than 10g/dL). * Thrombocytopenia (Platelet (Plt) less than 100,000/microl). * Absolute lymphocyte count (ALC) of greater than 5,000 cells/microL * Symptomatic splenomegaly. * Enlarging lymph nodes greater than 2cm. * Repeated infections requiring oral or intravenous (i.v.) antibiotics. * Patients who have eligible blood counts within 4 weeks from enrollment will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment. No prior purine analog therapy except up to 1 prior course of cladribine. No prior rituximab unless HCLv patient. Eastern Cooperative Oncology Group (ECOG) performance status (78) of 0-3. Patients must be able to understand and give informed consent. Women of child-bearing age and all men must use birth control of any type until at least 12 months after the last dose of therapy. Creatinine less than or equal to 1.5 or creatinine clearance greater than or equal to 60 ml/ml. Bilirubin less than or equal to 2 unless consistent with Gilbert's (total/direct greater than 5), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 times upper limits of normal. No other therapy (i.e. chemotherapy, interferon) for 4 weeks prior to study entry, or cladribine for 6 months prior to study entry. Age at least 18 Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months after completion of treatment. Subject has provided written informed consent Patients must be willing to co-enroll in the investigators companion protocol 10-C-0066 titled Collection of Human Samples to Study Hairy Cell and other Leukemias, and to Develop Recombinant Immunotoxins for Cancer Treatment.
Exclusion criteria
Presence of active untreated infection Uncontrolled coronary disease or New York Heart Association Classification (NYHA) class III-IV heart disease. Known infection with HIV. Hepatitis B is allowed only if viral load is undetectable and if on anti-hepatitis B therapy like Entecavir. Hepatitis C is allowed only if viral load is undetectable, and if the patient has received curative therapy. Patients with documented history of no response to cladribine, and without 50% improvement in platelets, hemoglobin or granulocytes. This exclusion does not apply to HCLv. These patients are eligible regardless of prior response to chlorodeoxyadenosine (CDA) Pregnant or lactating women. Presence of active 2nd malignancy requiring treatment. 2nd malignancies with low activity which do not require treatment (i.e. low-grade prostate cancer, basal cell or squamous cell skin cancer) do not constitute exclusions. Inability to comply with study and/or follow-up procedures. Presence of central nervous system (CNS) disease, which is symptomatic. At the Investigators discretion, receipt of a live vaccine within 4 weeks prior to randomization. Efficacy and/or safety of immunization during periods of B-cell depletion have not been adequately studied. It is recommended that a patients vaccination record and possible requirements be reviewed. Per the investigator's discretion, the patient may have any required vaccination/booster administered at least 4 weeks prior to the initiation of study treatment. Review of the patient s immunization status for the following vaccinations is recommended: tetanus; diphtheria; influenza; pneumococcal polysaccharide; Varicella; measles, mumps and rubella (MMR); and hepatitis B. Patients who are considered to be at high risk for hepatitis B virus (HBV) infection and for whom the investigator has determined that immunization is indicated should complete the entire HBV vaccine series at least 4 weeks prior to participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate Comparing Minimal Residual Disease (MRD) at 6 Months After Start of Treatment in Comparison Groups | Restaged 6 months after the start of treatment | Participants with newly diagnosed Hairy Cell Leukemia (HCL) and once relapsed HCL were split and both groups were randomized to receive either simultaneous treatment with Cladribine and Rituxan or Cladribine with Rituxan given no earlier than 6 months after cladribine as needed. Outcome measured by Bone Marrow and Blood Flow cytometry and histochemistry of the core biopsy at the 6 months after start of treatment time point. If all three were negative for hairy cells participants were in a minimal residual disease status (MRD). And were considered without HCL disease at that time point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimal Residual Disease (MRD)-Free Survival After Cladribine and up to 2 Courses of Rituximab | Testing done 6 months post first dose of treatment, then yearly x2 years and then every 2 years after cladribine indefinitely | Compare Cladribine + Rituxan vs cladribine alone in terms of MRD-free survival. MRD free survival time is the time until relapsing from MRD to -free to Complete response. Measured by blood and bone marrow flow cytometry, complete blood count (CBC), and bone marrow immunohistochemistry. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAEv3.0) | From first study intervention,Study Day 1, Cycle 1-30 days after study agent up to day 35 for participants receiving cladribine only, up to day 80 for participants receiving cladribine+rituximab, &up to day 80 for participants receiving delayed rituximab. | Here is the number of participants with serious and/or non-serious adverse events (AE's) assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Arm 1 SubGroup 1 -Cladribine + Rituximab Participants with Hairy Cell Leukemia (HCL) with (62 participants) and without (68 participants) prior course of purine analog to be randomized between Arm 1 and Arm 2 (randomization stratified based upon prior purine analog \[yes/no\]). Cladribine + Rituximab. | 34 |
| Cohort 1 Arm 1 SubGroup 2 -Cladribine + Rituximab Participants with Hairy Cell Leukemia (HCL) with (62 participants) and without (68 participants) prior course of purine analog to be randomized between Arm 1 and Arm 2 (randomization stratified based upon prior purine analog \[yes/no\]). Cladribine + Rituximab. | 32 |
| Cohort 1 Arm 2 SubGroup 1-Cladribine(+Rituximab After 6 Months if Minimal Residual Disease Detected) Participants with Hairy Cell Leukemia (HCL) with (62 participants) and without (68 participants) prior course of purine analog to be randomized between Arm 1 and Arm 2 (randomization stratified based upon prior purine analog \[yes/no\]). Cladribine (+ Rituximab after 6 months if minimal residual disease (MRD) detected). | 34 |
| Cohort 1 Arm 2 SubGroup 2-Cladribine(+Rituximab After 6 Months if Minimal Residual Disease Detected) Participants with Hairy Cell Leukemia (HCL) with (62 participants) and without (68 participants) prior course of purine analog to be randomized between Arm 1 and Arm 2 (randomization stratified based upon prior purine analog \[yes/no\]). Cladribine (+ Rituximab after 6 months if minimal residual disease (MRD) detected). | 30 |
| Cohort 2 Arm 3 SubGroup 1-Cladribine (Rituximab Before 1st of 5 Daily Doses of Cladribine on Day 1) Participants with Hairy Cell Leukemia (HCL) without prior course of purine analog to be directly assigned to Arm 3 (25 participants; after completion of the 68 participants without prior purine analog in Cohort 1). Cladribine + Rituximab (Rituximab will be administered just before rather than after the 1st of the 5 daily doses of cladribine | 25 |
| Cohort 3Arm3 HairyCell LeukemiaVariant-Cladribine +(Rituximab Before 1st of 5 Daily Doses Cladribine Participants with Hairy Cell Leukemia Variant (HCLv) to be directly assigned to Arm 3 (20 participants). Cladribine + Rituximab (Rituximab will be administered just before rather than after the 1st of the 5 daily doses of cladribine | 20 |
| Total | 175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death on study | 2 | 2 | 0 | 1 | 0 | 0 |
| Overall Study | Refused further treatment | 0 | 1 | 2 | 0 | 0 | 0 |
| Overall Study | Switched to alternative treatment | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 Arm 1 SubGroup 2 -Cladribine + Rituximab | Cohort 1 Arm 2 SubGroup 1-Cladribine(+Rituximab After 6 Months if Minimal Residual Disease Detected) | Cohort 1 Arm 2 SubGroup 2-Cladribine(+Rituximab After 6 Months if Minimal Residual Disease Detected) | Cohort 2 Arm 3 SubGroup 1-Cladribine (Rituximab Before 1st of 5 Daily Doses of Cladribine on Day 1) | Cohort 3Arm3 HairyCell LeukemiaVariant-Cladribine +(Rituximab Before 1st of 5 Daily Doses Cladribine | Cohort 1 Arm 1 SubGroup 1 -Cladribine + Rituximab | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 3 Participants | 6 Participants | 11 Participants | 5 Participants | 32 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 31 Participants | 27 Participants | 19 Participants | 9 Participants | 29 Participants | 143 Participants |
| Age, Continuous | 54.56 years STANDARD_DEVIATION 10.23 | 47.94 years STANDARD_DEVIATION 11.19 | 51.83 years STANDARD_DEVIATION 10.62 | 53.16 years STANDARD_DEVIATION 13.85 | 64.7 years STANDARD_DEVIATION 11.75 | 51.03 years STANDARD_DEVIATION 11.8 | 53.08 years STANDARD_DEVIATION 12.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 26 Participants | 28 Participants | 25 Participants | 20 Participants | 0 Participants | 128 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 32 Participants | 36 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) White | 32 Participants | 30 Participants | 26 Participants | 25 Participants | 18 Participants | 30 Participants | 161 Participants |
| Region of Enrollment United States | 32 participants | 34 participants | 30 participants | 25 participants | 20 participants | 34 participants | 175 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 8 Participants | 32 Participants |
| Sex: Female, Male Male | 30 Participants | 29 Participants | 24 Participants | 19 Participants | 15 Participants | 26 Participants | 143 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 34 | 2 / 32 | 0 / 34 | 1 / 30 | 0 / 25 | 5 / 20 |
| other Total, other adverse events | 34 / 34 | 31 / 32 | 34 / 34 | 29 / 30 | 24 / 25 | 19 / 20 |
| serious Total, serious adverse events | 4 / 34 | 2 / 32 | 2 / 34 | 5 / 30 | 4 / 25 | 3 / 20 |
Outcome results
Primary
Response Rate Comparing Minimal Residual Disease (MRD) at 6 Months After Start of Treatment in Comparison Groups
Participants with newly diagnosed Hairy Cell Leukemia (HCL) and once relapsed HCL were split and both groups were randomized to receive either simultaneous treatment with Cladribine and Rituxan or Cladribine with Rituxan given no earlier than 6 months after cladribine as needed. Outcome measured by Bone Marrow and Blood Flow cytometry and histochemistry of the core biopsy at the 6 months after start of treatment time point. If all three were negative for hairy cells participants were in a minimal residual disease status (MRD). And were considered without HCL disease at that time point.
Time frame: Restaged 6 months after the start of treatment
Population: Cohort 2, Arm 3 and Cohort 3, Arm 3 are not reported because the investigator is only comparing the randomized groups. The primary goal is comparing the randomization and Cohort 2 was not randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Arm 1 SubGroup 1 -Cladribine + Rituximab | Response Rate Comparing Minimal Residual Disease (MRD) at 6 Months After Start of Treatment in Comparison Groups | 97.1 Percentage of participants |
| Cohort 1 Arm 1 SubGroup 2 -Cladribine + Rituximab | Response Rate Comparing Minimal Residual Disease (MRD) at 6 Months After Start of Treatment in Comparison Groups | 62.5 Percentage of participants |
| Cohort 1 Arm 2 SubGroup 1-Cladribine(+Rituximab After 6 Months if Minimal Residual Disease Detected) | Response Rate Comparing Minimal Residual Disease (MRD) at 6 Months After Start of Treatment in Comparison Groups | 23.5 Percentage of participants |
| Cohort 1 Arm 2 SubGroup 2-Cladribine(+Rituximab After 6 Months if Minimal Residual Disease Detected) | Response Rate Comparing Minimal Residual Disease (MRD) at 6 Months After Start of Treatment in Comparison Groups | 3.3 Percentage of participants |
Secondary
Minimal Residual Disease (MRD)-Free Survival After Cladribine and up to 2 Courses of Rituximab
Compare Cladribine + Rituxan vs cladribine alone in terms of MRD-free survival. MRD free survival time is the time until relapsing from MRD to -free to Complete response. Measured by blood and bone marrow flow cytometry, complete blood count (CBC), and bone marrow immunohistochemistry.
Time frame: Testing done 6 months post first dose of treatment, then yearly x2 years and then every 2 years after cladribine indefinitely
Other Pre-specified
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAEv3.0)
Here is the number of participants with serious and/or non-serious adverse events (AE's) assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: From first study intervention,Study Day 1, Cycle 1-30 days after study agent up to day 35 for participants receiving cladribine only, up to day 80 for participants receiving cladribine+rituximab, &up to day 80 for participants receiving delayed rituximab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 Arm 1 SubGroup 1 -Cladribine + Rituximab | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAEv3.0) | 34 Participants |
| Cohort 1 Arm 1 SubGroup 2 -Cladribine + Rituximab | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAEv3.0) | 31 Participants |
| Cohort 1 Arm 2 SubGroup 1-Cladribine(+Rituximab After 6 Months if Minimal Residual Disease Detected) | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAEv3.0) | 34 Participants |
| Cohort 1 Arm 2 SubGroup 2-Cladribine(+Rituximab After 6 Months if Minimal Residual Disease Detected) | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAEv3.0) | 29 Participants |
| Cohort 2 Arm 3 SubGroup 1-Cladribine (Rituximab Before 1st of 5 Daily Doses of Cladribine on Day 1) | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAEv3.0) | 24 Participants |
| Cohort 3Arm3 HairyCell LeukemiaVariant-Cladribine +(Rituximab Before 1st of 5 Daily Doses Cladribine | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAEv3.0) | 19 Participants |