- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00694590
Study of AMD3100 (Plerixafor) and Rituximab in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Phase I Study of AMD3100 and Rituximab in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
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.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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La Jolla, California, United States
- UCSD Moores Cancer Center
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Ohio
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Columbus, Ohio, United States
- Ohio State University Comprehensive Cancer Center
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Texas
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Houston, Texas, United States
- UTMD Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: plerixafor
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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29 Days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The principal toxicities and dose limiting toxicities of plerixafor when combined with rituximab
Time Frame: 73 days
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73 days
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Time to maximal plasma concentration (Tmax) when plerixafor is combined with rituximab
Time Frame: Course 1 (4 weeks)
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Course 1 (4 weeks)
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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)]
|
Course 1 (4 weeks)]
|
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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)
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Course 1 (4 weeks)
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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)
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Course 1 (4 weeks)
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Half-life (T½) when plerixafor is combined with rituximab
Time Frame: Course 1 (4 weeks)
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Course 1 (4 weeks)
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Volume of distribution (Vz/F for subcutaneous (SC) administration; Vz for intravenous (IV) administration);
Time Frame: Course 1 (4 weeks)
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in the case of multiexponential disposition, volume of distribution at steady-state (Vss) will be calculated when plerixafor is combined with rituximab
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Course 1 (4 weeks)
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, B-Cell
- Lymphoma
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Anti-Infective Agents
- Antiviral Agents
- Anti-HIV Agents
- Anti-Retroviral Agents
- Plerixafor
Other Study ID Numbers
- MOZ00207
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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