Evaluation of the Safety and Efficacy of the Addition of AMD3100 to a G-CSF Mobilization Regimen in Patients With Lymphoma (NHL and HD) and Multiple Myeloma (MM).
Some patients with multiple myeloma or lymphoma will need treatment with high dose chemotherapy to treat their condition. This potent treatment will kill many of the blood-forming cells in the bone marrow. The patient will therefore need these blood-forming cells replaced after the chemotherapy treatment. This is done by collecting some of teh patients own blood-forming stem cells before chemotherapy, storing them and then infusing them into the patient after chemotherapy (in the same way as a blood transfusion is given). The stem cells will then make their way unto the bone marrow and re-populate it. Having stem cells collected and returned later is called an "Autologous Transplant".
In most patients these blood-forming stem cells (which normally live in the bone marrow) are "mobilized" into the blood stream where they are then collected by a process called apheresis (a bit like donating blood). This process of mobilization is not always successful. In this study patients who did not collect enough stem cells in a previous cell collection attempt to have an autologous stem cell transplant will participate. Patients will be mobilized with G-CSF (current standard treatment to mobilize stem cells) and the effect of adding AMD3100 to G-CSF will be studied by comparing outcomes in patients who get G-CDF with placebo (non-active substance which looks like AMD3100) to patients who get G-CSF with AMD3100.
AMD3100 is a member of a new class of medications called "chemokine inhibitors". The drug triggers the movement of stem cells out of the bone marrow into the blood stream. In previous studies with healthy volunteers and cancer patients, when AMD3100 and G-CSF were used in combination, a greater number of stem cells were mobilized into the blood stream than by using g-CSF alone.
The purposes of this study are to measure how many stem cells can be collected, the number of days to collect those cells and the safety of a mobilization regimen of AMD3100 with G-CSF compared to G-CSF with placebo. If enough cells are collected to have a transplant, the study will also evaluate how well the cells grow when transplanted.
|Lymphoma Non Hodgkin's Lymphoma Hodgkin's Disease Multiple Myeloma||Drug: Plerixafor (AMD3100) Drug: Can be any registered nonpegylated form of G-CSF||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Participant)
Primary Purpose: Treatment
|Official Title:||A Multicenter, Randomized, Comparative, Patient-blinded Study to Evaluate the Safety and Efficacy of G-CSF Alone Versus AMD3100 (240 µg/kg) Added to a G-CSF Mobilization Regimen in Adult Patients With Non-Hodgkin's Lymphoma (NHL), Hodgkins Disease (HD) or Multiple Myeloma (MM) Who Have Previously Failed Stem Cell Collections or Collection Attempts|
- To determine if patients reach a target of ≥ 2x10^6 CD34+ cells/kg within 2 days of apheresis in Non-Hodgkin's Lymphoma (NHL), Hodgkin's Disease (HD) or Multiple Myeloma (MM) patients who are proven poor mobilizer. [ Time Frame: after last apheresis ]
- To examine and compare the safety of both mobilization regimens, G-CSF plus AMD3100(240µg/kg) and G-CSF plus placebo in NHL, MM and HD patients. [ Time Frame: After each dose of AMD3100 ]
- To measure the daily and total number of CD34+ cells harvested during apheresis. [ Time Frame: After each dose of AMD3100 ]
- To measure the number of days of apheresis needed to harvest ≥ 2x10^6 CD34+ cells/kg. [ Time Frame: After each dose of AMD3100 transplantation and engraftment ]
- To measure the number of days of apheresis needed to harvest ≥ 5x10^6 CD34+ cells/kg. [ Time Frame: After each dose of AMD3100, transplantation and engraftment ]
- To determine the times of platelet (PLT) and polymorphonuclear leukocyte (PMN) engraftment. [ Time Frame: After each dose of AMD3100, transplantation and engraftment ]
- To evaluate the durability of engraftment. [ Time Frame: After each dose of AMD3100, transplantation and engraftment ]
- To determine if patient reach the Optimum Target of 5x10^6 CD34+ cells/kg within 4 days of apheresis. [ Time Frame: After each dose of AMD3100, transplantation and engraftment ]
- To determine if NHL tumor cells are mobilized after either G-CSF mobilization of AMD3100 administration [ Time Frame: After G-CSF mobilization period and after each dose of AMD3100 ]
|Study Start Date:||November 2007|
|Study Completion Date:||June 2009|
|Primary Completion Date:||April 2008 (Final data collection date for primary outcome measure)|
Experimental: AMD3100 added to a G-CSF Mobilisation regimen
AMD3100 added to a G-CSF Mobilisation regimen
Drug: Plerixafor (AMD3100)
0.24mg/kg SC for 2 to 7 days.
Active Comparator: G-CSF plus placebo
G-CSF plus placebo
Drug: Can be any registered nonpegylated form of G-CSF
10mcg/kg SC for 4 days followed by an additional 2 to 7 days.
This is a multicenter, randomized, comparative, patient-blinded study. Patients with NHL, HD or MM who would benefit from an autologous stem cell transplant, who failed previous collections or collection attempts with a mobilization regimen of chemotherapy with or wihoutG-CSF, and who meet the inclusion/exclusion criteria are eligible to receive AMD3100(240µg/kg) or placebo (both given as an evening dose).
Patients will undergo mobilization with G-CSF (10µg/kg) for 4 consecutive days. On Day 4, AMD3100 (240µg/kg) or placebo 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. G-CSF will be administered in the morning and approximately 1 hour prior to apheresis. Patients will undergo a minimum of 2 and a maximum of 7 aphereses until a minimum of 2x10^6 CD34+ cells/kg or greater than or equal to 5x10^6 CD34+cells/kg are collected. More cells may be collected, if done within the 7 aphereses. Patients who are to receive a tandem transplant will undergo a minimum of 2 and maximum of 7 aphereses until a minimum of 4x10^6 CD34+ cells/kg are collected. Aphereses should be performed on consecutive days (including weekend days)
The patient will have a peripheral blood (PB) sample collected to measure the number of CD34+ cell in PB at baseline prior to administration of G-CSF, prior to each administration of AMD3100 or placebo and at the initiation of apheresis. In addition, a sample will be obtained from each apheresis product to measure the number of CD34+ cells collected in the apheresis product.
Patients who fail to collect greater than or equal to 0.8x10^6 CD34+ cells/kg in 7 aphereses will be offered a rescue arm giving AMD3100 plus G-CSF.
Patients will undergo their ablative chemotherapy before transplantation. Patients will then be transplanted. The success of the transplantation will be evaluated. Graft durability will be evaluated to 12 months post-transplant. In the event that a sufficient number of cells for transplantation are not obtained from the collections, cells may be retained, pooled, and transplanted at a later date at the Investigator's discretion.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00665314
|Study Director:||Medical Monitor||Genzyme, a Sanofi Company|