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

NCT00694590 | Completed Phase 1

• 1 other identifier: MOZ00207
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

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.

Conditions

Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)

Keywords

AMD3100; Rituximab; Chronic Lymphocytic Leukemia; CLL; Small Lymphocytic Lymphoma; SLL

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• The principal toxicities and dose limiting toxicities of plerixafor when combined with rituximab

  73 days

• Time to maximal plasma concentration (Tmax) when plerixafor is combined with rituximab

  Course 1 (4 weeks)

• 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)]

• Area under the concentration-time curve over the dosing interval (τ) (AUC 0-τ) when plerixafor is combined with rituximab

  Course 1 (4 weeks)

• Area under the concentration-time curve from time zero to infinity (AUC 0-∞ ) when plerixafor is combined with rituximab

  Course 1 (4 weeks)

Study Arms (1)

plerixafor

EXPERIMENTAL

Drug: plerixafor

Interventions

plerixafor DRUG

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.

Also known as: Mozobil(TM), AMD3100

plerixafor

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (3)

UCSD Moores Cancer Center

La Jolla, California, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Location

UTMD Anderson Cancer Center

Houston, Texas, United States

Location

Related Publications (4)

• 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.

  RESULT

• 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.

  RESULT

• 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.

  PMID: 34398557 DERIVED

• 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.

  PMID: 31352850 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2008
• First Posted: June 10, 2008
• Study Start: June 1, 2008
• Primary Completion: November 1, 2010
• Study Completion: September 1, 2011
• Last Updated: March 20, 2015

Record last verified: 2015-03

Locations

US (3)