Study of AMD3100 (Plerixafor) and Rituximab in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Chronic Lymphocytic Leukemia (CLL) Clinical Trial

Official title:

Phase I Study of AMD3100 and Rituximab in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00694590
• Other study ID #: MOZ00207
• Status: Completed
• Phase: Phase 1
• First received: June 6, 2008
• Last updated: March 19, 2015
• Start date: June 2008
• Est. completion date: September 2011

Study information

• Verified date: March 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia (CLL)
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Small Lymphocytic Lymphoma (SLL)

Intervention

Drug:
• plerixafor
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.

Locations

Country	Name	City	State
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	UTMD Anderson Cancer Center	Houston	Texas
United States	UCSD Moores Cancer Center	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. Haematolo

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 leu

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		29 Days	Yes
Secondary	The principal toxicities and dose limiting toxicities of plerixafor when combined with rituximab		73 days	Yes
Secondary	Time to maximal plasma concentration (Tmax) when plerixafor is combined with rituximab		Course 1 (4 weeks)	No
Secondary	Area under the concentration-time curve from time zero to the last observed concentration (AUC 0-last) when plerixafor is combined with rituximab		Course 1 (4 weeks)]	No
Secondary	Area under the concentration-time curve over the dosing interval (t) (AUC 0-t) when plerixafor is combined with rituximab		Course 1 (4 weeks)	No
Secondary	Area under the concentration-time curve from time zero to infinity (AUC 0-8 ) when plerixafor is combined with rituximab		Course 1 (4 weeks)	No
Secondary	Half-life (T½) when plerixafor is combined with rituximab		Course 1 (4 weeks)	No
Secondary	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	Course 1 (4 weeks)	No