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
  Purpose

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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Drug: plerixafor
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of AMD3100 and Rituximab in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

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) [ Time Frame: 29 Days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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


Enrollment: 24
Study Start Date: June 2008
Study Completion Date: September 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: plerixafor 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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00694590

Locations
United States, California
UCSD Moores Cancer Center
La Jolla, California, United States
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
United States, Texas
UTMD Anderson Cancer Center
Houston, Texas, United States
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Publications:
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.

Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00694590     History of Changes
Other Study ID Numbers: MOZ00207
Study First Received: June 6, 2008
Last Updated: May 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Genzyme, a Sanofi Company:
AMD3100
Rituximab
Chronic Lymphocytic Leukemia
CLL
Small Lymphocytic Lymphoma
SLL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
JM 3100
Rituximab
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antineoplastic Agents
Antirheumatic Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014