AMD3100-2112: AMD3100 With G-CSF in Poor Mobilizing Adult Patients Who Previously Failed HSC Collection/Attempts

This study is currently recruiting patients.

Sponsored By:	Genzyme AnorMED Corporation, a wholly owned subsidiary of Genzyme
Information Provided By:	Genzyme
ClinicalTrials.gov Identifier:	NCT00396331

Purpose

Patients who would benefit from an autologous stem cell transplant, who have failed previous collections or collection attempts with a mobilization regimen of G-CSF alone, chemotherapy and G-CSF, or any other conventional therapy including cytokines, chemotherapy and cytokines and bone marrow harvests and who meet the inclusion/exclusion criteria are eligible to enter this study. The only change to standard of care of a mobilization regimen that includes G-CSF is the addition of a dose of AMD3100 on the evening prior to each day of apheresis.

Patients will undergo mobilization with G-CSF. On the 4th Day, AMD3100 will be administered in the evening prior to the first apheresis and each subsequent evening prior to apheresis thereafter. Patients will continue to receive G-CSF on each day of apheresis. Patients will undergo a minimum of 2 and a maximum of 7 aphereses or until ≧2 x 10e6 CD34+ cells/kg are collected, whichever occurs first.

If enough cells are collected the patient will be treated with high-dose chemotherapy in preparation for transplantation. Patients will be transplanted with cells obtained from the G-CSF with AMD3100 mobilization regimen.

Condition	Intervention	Phase
Multiple Myeloma Non-Hodgkin's Lymphoma	Drug:AMD3100 Procedure: Stem Cell Mobilization	Phase II

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Official Title: A Phase 2, Multicenter, Open-Label Study to Evaluate the Safety and Efficacy of AMD3100 (240 µg/kg) Added to a G-CSF Mobilization Regimen in Poor Mobilizing Adult Patients Who Have Previously Failed Stem Cell Collection/Attempts

Further Study Details:

Primary Outcomes: To determine if AMD3100, given with a G-CSF mobilizing regimen, is generally safe and well tolerated.; To determine the percentage of patients who previously failed mobilization with conventional methods who are successfully mobilized by AMD3100 given with G-CSF.

Secondary Outcomes: To determine the times of PLT and PMN engraftment; To evaluate the durability of engraftment at 3, 6 and 12 months post-transplant; To examine the pharmacokinetics of repeated doses of AMD3100

Expected Total Enrollment: 25

Study Start: 2005-10

This is a Phase 2, multicenter, prospective, observational, open-label study. Patients who would benefit from an autologous stem cell transplant, who have failed previous collections or collection attempts with a mobilization regimen of G-CSF alone, chemotherapy and G-CSF, or any other conventional therapy including cytokines, chemotherapy and cytokines and bone marrow harvests and who meet the inclusion/exclusion criteria are eligible to receive AMD3100 as outlined in this protocol. The only change to standard of care of a mobilization regimen that includes G-CSF is the addition of a dose of AMD3100 on the evening prior to each day of apheresis.

Patients will undergo mobilization with G-CSF (10 µg/kg) for 4 days. On Day 4, AMD3100 (240 µg/kg) will be administered in the evening prior to the first apheresis and each subsequent evening prior to apheresis thereafter, such that there is a 10 to 11 hour interval between dosing and the initiation of apheresis. Patients will continue to receive G-CSF on each day of apheresis. Patients will undergo a minimum of 2 and a maximum of 7 aphereses or until ≧2 x 10e6 CD34+ cells/kg are collected, whichever occurs first. In addition, the mobilization of NHL tumor cells and the pharmacokinetics of repeat doses of AMD3100 will be examined.

After the last apheresis has been completed, or after the patient has collected ≧2 x 10e6 CD34+ cells/kg, he/she will be treated with high-dose chemotherapy in preparation for transplantation. Patients will be transplanted with cells obtained from the G-CSF with AMD3100 mobilization regimen. In the event that the minimum number of ≧2 x 10e6 cells for transplantation are not obtained from the first mobilization with AMD3100, cells may be retained and pooled for transplantation with those from a second mobilization with AMD3100, at the investigator’s discretion. If a second mobilization with AMD3100 is attempted, a minimum rest interval of one week should be allowed between the last apheresis of the first regimen and the first dose of G-CSF of the second. The number of CD34+ cells mobilized in the peripheral blood (PB), collected in the apheresis product, and the number of apheresis sessions performed will be measured. Success of the trasnplantation will be evaluated.

Eligibility

Ages Eligible for Study: 18 Years - 78 Years

Genders Eligible for Study: Both

Criteria

Inclusion Criteria:

Age 18 to 78 years

Eligible to undergo autologous transplantation

Has failed previous collections or collection attempts with a mobilization regimen of G-CSF, chemotherapy and G-CSF or any other conventional therapy including cytokines, chemotherapy and cytokines or bone marrow harvest.

ECOG performance status of 0 or 1

≧3 weeks since last cycle of chemotherapy (thalidomide, dexamethasone, and Velcade™ are not considered prior chemotherapy for the purpose of this study) NOTE: Although thalidomide, dexamethasone, and Velcade™ are not considered prior chemotherapy for the purpose of this study, none are to be administered within 7 days prior to the first dose of G-CSF (see Exclusion Criteria).

The patient has recovered from all acute toxic effects of prior chemotherapy

WBC >2.5 x 10e9/l

Absolute neutrophil count >1.5 x 10e9/l

Platelet count >85 x 10e9/l

Serum creatinine ≦1.5 mg/dl

Creatinine clearance >60 ml/min

SGOT, SGPT and total bilirubin <2x upper limit of normal

Left ventricle ejection fraction >45% (by normal ECHO or MUGA scan)

FEV1 >60% of predicted or DLCO ≧45% of predicted

No active infection of hepatitis B or C

Negative for HIV

Signed informed consent

Women of child-bearing potential agree to use an approved form of contraception

Exclusion Criteria

Diagnosis of AML or CLL.

A co-morbid condition which, in the view of the investigators, renders the patient at high risk from treatment complications

A residual acute medical condition resulting from prior chemotherapy

Received thalidomide, dexamethasone, and/or Velcade™ within 7 days prior to the first dose of G-CSF

Brain metastases or carcinomatous meningitis

Acute infection

Fever (temperature >38°C/100.4°F)

Hypercalcaemia (>1 mg/dl above the ULN)

Positive pregnancy test in female patients

Lactating females

Patients of child-bearing potential unwilling to implement adequate birth control

Patients whose actual body weight exceeds 175% of their ideal body weight

Patients who previously received experimental therapy within 4 weeks of enrolling in this protocol or who are currently enrolled in another experimental protocol during the Mobilization phase

Location and Contact Information

United States, California
City of Hope National Medical Center, Duarte, California, 91010, United States; Recruiting

Florida
H. Lee Moffitt Cancer Center, Tampa, Florida, 33612-9497, United States; Recruiting

Georgia
Blood & Marrow Transplant Group of Georgia, Atlanta, Georgia, 30342, United States; Recruiting

United States, Michigan
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, 48109-0473, United States; Recruiting

United States, Mississippi
University of Mississippi Medical Center, Div of Hematology, Jackson, Mississippi, 39216, United States; Recruiting

Missouri
Kansas City Cancer Centers, Kansas City, Missouri, 64111, United States; Recruiting

United States, New Jersey
Hackensack University Medical Center, Hackensack, New Jersey, 07601, United States; Recruiting

Virginia
Virginia Commonwealth University - Massey Cancer Center, Richmond, Virginia, 23298-0037, United States; Recruiting

United States, Wisconsin
University of Wisconsin, Blood and Bone Marrow Transplant, Madison, Wisconsin, 53792-5156, United States; Recruiting

More Information

Study ID Numbers: AMD3100-2112
ClinicalTrials.gov Identifier: NCT00396331
Health Authority: United States: Food and Drug Administration