Back to resultsStudy of AMD3100 (Plerixafor) and Rituximab in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Primary Purpose
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
plerixafor
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia (CLL) focused on measuring AMD3100, Rituximab, Chronic Lymphocytic Leukemia, CLL, Small Lymphocytic Lymphoma, SLL
Eligibility Criteria
Inclusion Criteria:
- Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period or be surgically sterile. Males must agree to abstain from sexual activity or agree to utilize a medically approved contraception method during treatment and for 3 months after the treatment period or be surgically sterile.
- Diagnosis of CLL or SLL, relapsed from at least one prior therapy.
- CLL/SLL cells expressing CD20 documented during screening.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
- Life expectancy of at least 12 weeks.
- Serum creatinine ≤2.0 mg/dL.
- Total bilirubin ≤2.0 mg/dL.
- ALT (alanine aminotransferase) and AST (aspartate aminotransaminase) ≤2 times the upper limit of normal (ULN); for patients with liver involvement of CLL/SLL disease, this limit is increased to ≤5 times the ULN.
- At the time of enrollment, patients must be >4 weeks since major surgery, radiotherapy, chemotherapy (>6 weeks for some chemotherapies), immunotherapy, biotherapy/targeted or investigational therapies and recovered from the toxicity of prior treatment to ≤ grade 1.
Exclusion Criteria:
- White Blood Cells (WBC) >250 x 10^9 cells/L.
- Disease refractory to rituximab therapy- defined as a failure to respond to prior rituximab-containing regimen.
- Women who are breastfeeding.
- Active viral hepatitis.
- Active infection or treatment with antimicrobial or antiviral therapy within 1 week of enrollment with the exception of prophylactic therapy.
- History of prior allergic reaction to plerixafor or rituximab.
- Significant lung disease.
- Serious cardiac disease such as a history of sustained ventricular arrhythmia, uncontrolled and serious congestive heart failure (CHF), angina, acute coronary syndrome, or myocardial infarction within 6 months of enrollment or other significant medical or psychosocial conditions that warrants exclusion.
Sites / Locations
- UCSD Moores Cancer Center
- Ohio State University Comprehensive Cancer Center
- UTMD Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
plerixafor
Arm Description
Outcomes
Primary Outcome Measures
The maximum tolerated dose of plerixafor when combined with rituximab as treatment for previously treated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
Secondary Outcome Measures
The principal toxicities and dose limiting toxicities of plerixafor when combined with rituximab
Time to maximal plasma concentration (Tmax) when plerixafor is combined with rituximab
Area under the concentration-time curve from time zero to the last observed concentration (AUC 0-last) when plerixafor is combined with rituximab
Area under the concentration-time curve over the dosing interval (τ) (AUC 0-τ) when plerixafor is combined with rituximab
Area under the concentration-time curve from time zero to infinity (AUC 0-∞ ) when plerixafor is combined with rituximab
Half-life (T½) when plerixafor is combined with rituximab
Volume of distribution (Vz/F for subcutaneous (SC) administration; Vz for intravenous (IV) administration);
in the case of multiexponential disposition, volume of distribution at steady-state (Vss) will be calculated when plerixafor is combined with rituximab
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00694590
Brief Title
Study of AMD3100 (Plerixafor) and Rituximab in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Official Title
Phase I Study of AMD3100 and Rituximab in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
September 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this research study is to determine if plerixafor can make CLL/SLL (Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma) cells more sensitive to being killed by rituximab, an anti-cancer drug that is commonly used in treating CLL and SLL. In this study, plerixafor will be added to standard treatment with rituximab. Subjects will be monitored to see how well they tolerate the use of these drugs together and how well they work to treat the leukemia.
The primary objective is to determine the maximum tolerated dose (MTD) of plerixafor when combined with rituximab as treatment for previously treated patients with CLL or SLL.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Keywords
AMD3100, Rituximab, Chronic Lymphocytic Leukemia, CLL, Small Lymphocytic Lymphoma, SLL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
plerixafor
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
plerixafor
Other Intervention Name(s)
Mozobil(TM), AMD3100
Intervention Description
Drug Course 1: plerixafor (20mg/mL). Dose escalation starting with 80 mcg/kg then 160, 240, 320, 420, and 540 mcg/kg, or to de-escalate to 40mcg/kg. Dosing 3 times/week for 3 weeks beginning at start of second week. Rituximab is also administered 3 times per week for 4 weeks using a fixed dose of 100 mg on Day 1 and a dose of 375 mg/m2 for all subsequent doses.
Drug Course 2: plerixafor (20 mg/m) same dose as course 1. Dosing 3 times/week for 4 weeks. Rituximab is also administered 3 times per week for 4 weeks using a dose of 375 mg/m2 for all doses.
Primary Outcome Measure Information:
Title
The maximum tolerated dose of plerixafor when combined with rituximab as treatment for previously treated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
Time Frame
29 Days
Secondary Outcome Measure Information:
Title
The principal toxicities and dose limiting toxicities of plerixafor when combined with rituximab
Time Frame
73 days
Title
Time to maximal plasma concentration (Tmax) when plerixafor is combined with rituximab
Time Frame
Course 1 (4 weeks)
Title
Area under the concentration-time curve from time zero to the last observed concentration (AUC 0-last) when plerixafor is combined with rituximab
Time Frame
Course 1 (4 weeks)]
Title
Area under the concentration-time curve over the dosing interval (τ) (AUC 0-τ) when plerixafor is combined with rituximab
Time Frame
Course 1 (4 weeks)
Title
Area under the concentration-time curve from time zero to infinity (AUC 0-∞ ) when plerixafor is combined with rituximab
Time Frame
Course 1 (4 weeks)
Title
Half-life (T½) when plerixafor is combined with rituximab
Time Frame
Course 1 (4 weeks)
Title
Volume of distribution (Vz/F for subcutaneous (SC) administration; Vz for intravenous (IV) administration);
Description
in the case of multiexponential disposition, volume of distribution at steady-state (Vss) will be calculated when plerixafor is combined with rituximab
Time Frame
Course 1 (4 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period or be surgically sterile. Males must agree to abstain from sexual activity or agree to utilize a medically approved contraception method during treatment and for 3 months after the treatment period or be surgically sterile.
Diagnosis of CLL or SLL, relapsed from at least one prior therapy.
CLL/SLL cells expressing CD20 documented during screening.
Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
Life expectancy of at least 12 weeks.
Serum creatinine ≤2.0 mg/dL.
Total bilirubin ≤2.0 mg/dL.
ALT (alanine aminotransferase) and AST (aspartate aminotransaminase) ≤2 times the upper limit of normal (ULN); for patients with liver involvement of CLL/SLL disease, this limit is increased to ≤5 times the ULN.
At the time of enrollment, patients must be >4 weeks since major surgery, radiotherapy, chemotherapy (>6 weeks for some chemotherapies), immunotherapy, biotherapy/targeted or investigational therapies and recovered from the toxicity of prior treatment to ≤ grade 1.
Exclusion Criteria:
White Blood Cells (WBC) >250 x 10^9 cells/L.
Disease refractory to rituximab therapy- defined as a failure to respond to prior rituximab-containing regimen.
Women who are breastfeeding.
Active viral hepatitis.
Active infection or treatment with antimicrobial or antiviral therapy within 1 week of enrollment with the exception of prophylactic therapy.
History of prior allergic reaction to plerixafor or rituximab.
Significant lung disease.
Serious cardiac disease such as a history of sustained ventricular arrhythmia, uncontrolled and serious congestive heart failure (CHF), angina, acute coronary syndrome, or myocardial infarction within 6 months of enrollment or other significant medical or psychosocial conditions that warrants exclusion.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
UCSD Moores Cancer Center
City
La Jolla
State/Province
California
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
UTMD Anderson Cancer Center
City
Houston
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Citations:
Citation
Andritsos L, Byrd J, Jones J, Hewes B, Kipps T, Hsu F, Burger J. Preliminary results from a phase I dose escalation study to determine the maximum tolerated dose of plerixafor in combination with rituximab in patients with relapsed chronic lymphocytic leukemia. American Society of Hematology, 2010, abstract 2450.
Results Reference
result
Citation
Andritsos L, Byrd J, Hewes B, Kipps T, Burger J. Preliminary results from a phase I dose escalation study to determine the maximum tolerated dose of plerixafor in combination with rituximab in patients with relapsed chronic lymphocytic leukemia. Haematologica 2010, 95[suppl.2]:321, abstract 0772.
Results Reference
result
PubMed Identifier
34398557
Citation
Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536.
Results Reference
derived
PubMed Identifier
31352850
Citation
Andritsos LA, Byrd JC, Cheverton P, Wu J, Sivina M, Kipps TJ, Burger JA. A multicenter phase 1 study of plerixafor and rituximab in patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2019 Dec;60(14):3461-3469. doi: 10.1080/10428194.2019.1643463. Epub 2019 Jul 27.
Results Reference
derived
Learn more about this trial
Study of AMD3100 (Plerixafor) and Rituximab in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
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