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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00694590
First received: June 6, 2008
Last updated: May 16, 2012
Last verified: May 2012

June 6, 2008
May 16, 2012
June 2008
November 2010   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
  • Study Part 1: To determine the maximum tolerated dose of AMD3100 when used with rituximab for treatment for previously treated patients with CLL or SLL [ Time Frame: Ongoing over the course of Part 1 of the study ]
  • Study Part 2: To assess response to treatment using the 1996 NCIWG criteria for subjects with CLL and NCI IWG criteria for subjects with SLL [ Time Frame: 1 and 3 months following completion of study treatment ]
Complete list of historical versions of study NCT00694590 on ClinicalTrials.gov Archive Site
  • The principal toxicities and dose limiting toxicities of plerixafor when combined with rituximab [ Time Frame: 73 days ] [ Designated as safety issue: Yes ]
  • Time to maximal plasma concentration (Tmax) when plerixafor is combined with rituximab [ Time Frame: Course 1 (4 weeks) ] [ Designated as safety issue: No ]
  • 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)] ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Half-life (T½) when plerixafor is combined with rituximab [ Time Frame: Course 1 (4 weeks) ] [ Designated as safety issue: No ]
  • Volume of distribution (Vz/F for subcutaneous (SC) administration; Vz for intravenous (IV) administration); [ Time Frame: Course 1 (4 weeks) ] [ Designated as safety issue: No ]
    in the case of multiexponential disposition, volume of distribution at steady-state (Vss) will be calculated when plerixafor is combined with rituximab
  • Study Part 1: To determine the adverse effects and dose limiting adverse effects of AMD3100 when used with rituximab [ Time Frame: Ongoing over the course of Part 1 of the study ]
  • Study Part 2: subject survival without disease progression, subject survival, duration of responses to treatment [ Time Frame: Every 3 months for up to 2 years for patients who have at least stable disease ]
  • Study Parts 1 and 2: To determine the pharmacokinetics of AMD3100 when used with rituximab
Not Provided
Not Provided
 
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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Chronic Lymphocytic Leukemia (CLL)
  • Small Lymphocytic Lymphoma (SLL)
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.

Other Names:
  • Mozobil(TM)
  • AMD3100
Experimental: plerixafor
Intervention: Drug: plerixafor
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
September 2011
November 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00694590
MOZ00207
No
Genzyme, a Sanofi Company
Genzyme, a Sanofi Company
Not Provided
Study Director: Medical Monitor Genzyme, a Sanofi Company
Genzyme, a Sanofi Company
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP