AMD3100-2109: AMD3100 in MM or NHL Patients Predicted to be Unable to Mobilize ≧2x10e6 CD34+ Cells in 3 Apheresis Days With G-CSF

This study has been terminated.

Sponsored By:	Genzyme AnorMED Corporation, a wholly owned subsidiary of Genzyme
Information Provided By:	Genzyme
ClinicalTrials.gov Identifier:	NCT00395967

Purpose

This Phase 2 observational study assesses further the safety and hematological activity of AMD3100 in patients with non-Hodgkin’s lymphoma (NHL) or multiple myeloma (MM) who are predicted to be unable to mobilize ≧2 x 10e6 CD34+ cells/kg within 3 apheresis days. Eligible to enter the study are NHL and MM patients who have undergone a cyto reductive chemotherapy regimen protocol, who are to undergo autologous transplantation, and who meet the inclusion/exclusion criteria. The only change to the standard of care is the addition of AMD3100 to a G-CSF mobilization regimen on the day prior to apheresis.

Eligible patients will undergo mobilization with G CSF (10 µg/kg qd) for 5 days and their peripheral blood (PB) CD34+ cell count will be measured on the fifth day.

If the peripheral CD34+ cell count is <5 cells/µl or ≧20 cells/µl, the patient will not enter this study and will be treated as per the policy of the study site.

If the peripheral CD34+ cell count is 5 to 7 cells/µl, the patient will not undergo apheresis that day, but will receive a dose of AMD3100 in the evening prior to receiving G-CSF and undergoing apheresis the next morning. The evening dosing with AMD3100 followed the next morning by G-CSF and apheresis will be repeated for up to a total of 3 days of apheresis or until ≧5 x 10e6 cells/kg are collected.

If the peripheral CD34+ cell count is 8 to 19 cells/µl, the patient will undergo apheresis that day. If this apheresis yield is <1.3 x 10e6 CD34+ cells/kg he/she may enter the study. If the apheresis yield on Day 5 is ≧1.3 x 10e6 CD34+ cells/kg, then the patient will not enter the study.

Day 6 patients who proceed in this study will receive a dose of G-CSF and apheresis after the previous evening AMD3100 dose. If the apheresis yield is at least double the yield on Day 5, the pm dose of AMD3100 and morning G-CSF sequence will be repeated up to a total of 3 days of apheresis or until ≧5 x 10e6 cells/kg are collected.

All patients, after the completion of apheresis procedures (or after ≧5 x 10e6 cells/kg are collected), will be treated with high-dose chemotherapy in preparation for transplant. Patients will be transplanted with cells collected after receiving AMD3100 with G-CSF. Success of the transplant will be evaluated by the times to PMN and PLT engraftment and by graft durability.

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

Study Type: Interventional

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

Official Title: Effect of AMD3100 (240µg/kg) on the Apheresis Yield of CD34+ Cells When Given To Multiple Myeloma or Non-Hodgkin’s Lymphoma Patients Predicted to be Unable to Mobilize ≧2 x 10e6 CD34+ Cells in Three Apheresis Days When Given G-CSF Alone

Further Study Details:

Primary Outcomes: To assess, among patients with a circulating CD34+ count <20 cells/µl after 5 days of mobilization with G-CSF alone, the percentage of patients who achieve ≧2 x 10e6 CD34+ cells/kg within 3 days of apheresis after receiving AMD3100 with G-CSF.

Secondary Outcomes: To evaluate if AMD3100 is generally safe.; To investigate the hematological activity of AMD3100.; To determine the times of PMN and PLT engraftment.; To determine the durability of engraftment.

Expected Total Enrollment: 5

Study Start: 2005-03; Study Completion: 2006-08

This is a Phase 2, observational, single-center, open-label study to further assess the safety and hematological activity of AMD3100 in patients with non-Hodgkin’s lymphoma (NHL) or multiple myeloma (MM) who are predicted to be unable to mobilize ≧2 x 10e6 CD34+ cells/kg within 3 apheresis days. NHL and MM patients who have undergone a cyto reductive chemotherapy regimen protocol, who are to undergo autologous transplantation, and who meet the inclusion/exclusion criteria are eligible to enter the study. The only change to the standard of care is the addition of AMD3100 to a G-CSF mobilization regimen on the day prior to apheresis.

Following screening procedures, eligible patients will undergo mobilization with G-CSF (10 µg/kg qd) for 5 days and their peripheral blood (PB) CD34+ cell count will be measured on the fifth day.
On Day 5, if the patient’s peripheral CD34+ cell count is <5 cells/µl or ≧20 cells/µl, then he/she will not enter this study and will be treated as per the policy of the study site.

On Day 5, if the patient’s peripheral CD34+ cell count is 5 to 7 cells/µl (inclusive), then he/she will not undergo apheresis that day, but will receive a dose of 240 µg/kg AMD3100 in the evening (approximately 10:00 pm) prior to receiving G-CSF and undergoing apheresis the next morning. The evening dosing with AMD3100 followed the next morning by G-CSF and apheresis will be repeated for up to a total of 3 days of apheresis or until ≧5 x 10e6 cells/kg are collected.

On Day 5, if the patient’s peripheral CD34+ cell count is 8 to 19 cells/µl (inclusive), then he/she will undergo apheresis that day. If this apheresis yield is <1.3 x 10e6 CD34+ cells/kg then the patient is predicted to be unlikely to collect ≧2 x 10e6 CD34+ cells/kg in ≦3 days of apheresis and he/she may enter the study; he/she will receive a dose of 240 µg/kg AMD3100 that evening at approximately 10:00 pm. However, if the apheresis yield on Day 5 is ≧1.3 x 10e6 CD34+ cells/kg, then the patient will not enter the study.

The next morning (Day 6), eligible patients will receive a dose of G-CSF (10 µg/kg) and will begin apheresis approximately 10 to 11 hours after the previous evening AMD3100 dose. If the apheresis yield is at least double the apheresis yield on Day 5, then he/she will receive another 10:00 pm dose of AMD3100 and have another apheresis performed the next morning (Day 7) after receiving G-CSF. The patient will repeat the evening dose of AMD3100 followed the next morning by G-CSF and apheresis for up to a total of 3 days of apheresis or until ≧5 x 10e6 cells/kg are collected.

All patients, after the completion of apheresis procedures (or after ≧5 x 10e6 cells/kg are collected), will be treated with high-dose chemotherapy in preparation for transplantation. Patients will be transplanted with cells collected after receiving AMD3100 with G-CSF. However, if there are insufficient cells, then cells collected after receiving AMD3100 with G-CSF may be pooled with cells collected after receiving G-CSF alone.

Safety will be evaluated by physical exam, adverse events/serious adverse events, concomitant medications, injection site assessment, hematology, chemistry, and urinalysis.

Hematological activity of AMD3100 will be evaluated by the number of CD34+ cells mobilized in the peripheral blood just prior to the time of the AMD3100 dosing and prior to apheresis, and the number of CD34+ cells harvested in the apheresis product. In addition, success of the transplantation will be evaluated by the times to PMN and PLT engraftment and by graft durability.

Eligibility

Ages Eligible for Study: 18 Years - 75 Years

Genders Eligible for Study: Both

Criteria

Inclusion Criteria:

Diagnosis of NHL or MM

Eligible for autologous transplantation

≦3 prior regimens of chemotherapy (Rituxan is not considered chemotherapy for the purpose of this study)

>4 weeks since last cycle of chemotherapy (Rituxan is not considered chemotherapy for the purpose of this study)

Total dose of melphalan ≦200 mg

ECOG performance status of 0 or 1

Recovered from all acute toxic effects of prior chemotherapy

WBC count >3.0 x 10e9/l prior to first dose of G-CSF

Absolute PMN count >1.5 x 10e9/l prior to first dose of G-CSF

PLT count >100 x 10e9/l prior to first dose of G-CSF

Serum creatinine ≦2.2 mg/dl

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

Cardiac and pulmonary status sufficient to undergo apheresis and transplantation

Negative for HIV

Signed informed consent

Patients of childbearing potential agree to use an approved form of contraception

CD34+ cell count between 5 and 19 CD34+ cells/ml after 5 days of mobilization with G CSF alone

Exclusion Criteria

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

Failed previous stem cell collection or collection attempts

A residual acute medical condition resulting from prior chemotherapy

Active brain metastases or carcinomatous meningitis

Active infection requiring antibiotic treatment

Received prior radio-immunotherapy with Zevalin or Bexxar

Received bone-seeking radionuclides (e.g., holmium)

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

Fever (temperature >38 °C/100.4 °F)

Positive pregnancy test in female patients

Lactating females

History of ventricular arrhythmias, including ECG-documented PVCs, during the last 3 years

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

(Applicable only to patients who, after 5 days of G-CSF mobilization, have PB CD34+ count of 8-19 cells/µl inclusive) Had an apheresis yield ≧1.3 x 10e6 CD34+ cells/kg on Day 5.

Location Information

United States, North Carolina
Duke University Medical Center - Adult BMT Program, Durham, North Carolina, 27705, United States

More Information

Study ID Numbers: AMD3100-2109
ClinicalTrials.gov Identifier: NCT00395967
Health Authority: United States: Food and Drug Administration