Ignite Creation Date:
2024-05-05 @ 9:37 PM
Last Modification Date:
2024-10-26 @ 10:07 AM
Study NCT ID:
NCT00923013
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-07-01
First Post:
2009-06-17
Brief Title:
Cladribine With Simultaneous or Delayed Rituximab to Treat Hairy Cell Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Randomized Trial of Cladribine CdA With Simultaneous or Delayed Rituximab to Eliminate Hairy Cell Leukemia Minimal Residual Disease
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-09-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 CD25-negative variant HCLv respond poorly to initial cladribine but do respond to rituximab in anecdotal reports
Deoxycytidine kinase phosphorylates cladribine to CdATP which incorporates into DNA leading to DNA strand breaks and inhibition of DNA synthesis Rituximab is an anti-CD20 monoclonal antibody which induces apoptosis and either complement or antibody dependent cytotoxicity ADCC or 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 FACS or PCR using consensus primers The most sensitive HCL MRD test is real-time quantitative PCR using sequence-specific primers 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 Cancergov 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 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 andor rituximab correlate with response and clinical endpoints
To determine using MRD and tumor marker data when 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 015 mgKgday times 5 doses each by 2hr iv infusion days 1-5
Rituximab 375 mgm2week 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 CLIA certified Blood MRD relapse is defined as FACS positivity or low blood counts ANC less than 1500microl Plt less than 100000microl or 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
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 CD25-negative variant HCLv respond poorly to initial cladribine but do respond to rituximab in anecdotal reports
Deoxycytidine kinase phosphorylates cladribine to CdATP which incorporates into DNA leading to DNA strand breaks and inhibition of DNA synthesis Rituximab is an anti-CD20 monoclonal antibody which induces apoptosis and either complement or antibody dependent cytotoxicity ADCC or 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 FACS or PCR using consensus primers The most sensitive HCL MRD test is real-time quantitative PCR using sequence-specific primers 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 Cancergov 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 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 andor rituximab correlate with response and clinical endpoints
To determine using MRD and tumor marker data when 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 015 mgKgday times 5 doses each by 2hr iv infusion days 1-5
Rituximab 375 mgm2week 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 CLIA certified Blood MRD relapse is defined as FACS positivity or low blood counts ANC less than 1500microl Plt less than 100000microl or 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 CD25-negative 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 DNA synthesis selectively in HCL cells Cladribine is effective after just 1 cycle Rituximab is an anti-CD20 monoclonal antibody which induces apoptosis and either complement or antibody dependent cytotoxicity ADCC or 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 FACS or PCR using consensus primers The most sensitive HCL MRD test is real-time quantitative PCR using sequence-specific primers 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 Cancergov 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 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 015 mgKgday times 5 doses each by 2hr iv infusion days 1-5
Rituximab 375 mgm2week 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 CLIA certified Blood MRD relapse is defined as FACS positivity or low blood counts ANC less than 1500microl Plt less than 100000microl or 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
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 CD25-negative 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 DNA synthesis selectively in HCL cells Cladribine is effective after just 1 cycle Rituximab is an anti-CD20 monoclonal antibody which induces apoptosis and either complement or antibody dependent cytotoxicity ADCC or 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 FACS or PCR using consensus primers The most sensitive HCL MRD test is real-time quantitative PCR using sequence-specific primers 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 Cancergov 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 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 015 mgKgday times 5 doses each by 2hr iv infusion days 1-5
Rituximab 375 mgm2week 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 CLIA certified Blood MRD relapse is defined as FACS positivity or low blood counts ANC less than 1500microl Plt less than 100000microl or 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 09-C-0005 | None | None | None |