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
18 Years
78 Years
Both
Lymphoma, Non Hodgkin's Lymphoma, Hodgkin's Disease, Multiple Myeloma
Trial Information
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
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.
Inclusion Criteria:
- Eligible to undergo autologous transplantation.
- Diagnosis of NHL, HD or MM [patients with plasma cell leukemia or other leukemias
including chronic lymphocytic leukemia (CLL), are excluded].
- In the last collection attempt prior to entry into this trial, the patient has failed
to collect 0.8x10^6 cells/kg in at least 2 apheresis sessions or 2x10^6 cells/kg in 4
apheresis sessions using a mobilization regimen of chemotherapy, with or without
G-CSF.
- A minimum of a 7 day interval between last collection attempt and randomization.
- Cardiac, pulmonary and renal function deemed clinically adequate to be able to
undergo mobilization and transplant.
- Performance status, Eastern Cooperative Oncology Group (ECOG) of 0 or 1
- ≥ 21 days between the last cycle of chemotherapy and randomization (thalidomide,
dexamethasone, and other corticosteroids, Rituxan® and Velcade® are not considered
prior chemotherapy for the purpose of this study).
- The patient has recovered from all acute toxic effects of prior chemotherapy.
- WBC ≥ 2.5x10^9/l.
- Absolute neutrophil count ≥ 1.5x10^9/l.
- Platelet count ≥ 75x10^9/l.
- Adequate renal function as demonstrated by serum creatine ≤ or equal to 2.2 mg/dl or
creatinine clearance (24 hr urine collection)≥ 60 ml/min
- Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate
Transaminase (SGPT) and total bilirubin ≤ 2.5 x upper limit of normal (ULN).
- Signed informed consent.
- All patients must agree to use a highly effective method of contraception (including
both female patients of child-bearing potential and male patients with child-bearing
potential partners). Effective birth control includes: a) birth control pills,
depo-progesterone, or an IUD PLUS one barrier method, or b) two barrier methods.
Effective barrier methods are: male and female condoms, diaphragms, and spermicides
(creams or gels that contain a chemical to kill sperm). For patients using hormonal
contraceptive method, information about any interaction of MAD3100 with hormonal
contraceptives is not known.
Exclusion Criteria:
- 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 or corticosteroids, Rituxan® and Velcade® within
7 days prior to randomization.
- Brain metastases or carcinomatous meningitis.
- Active acute or chronic infection or anti-infective therapy within 1 week prior to
randomization.
- Fever (temperature ≥ 38 degrees celsius).
- Hypercalcemia (≥ 1mg/dl above the ULN).
- Known to be HIV-positive.
- Pregnant and nursing females.
- Patient unwilling to implement adequate birth control (including both female patients
of child-bearing potential and male patients with child-bearing potential partners).
- Patients who previously received experimental therapy within 4 weeks of randomization
or who are currently enrolled in another experimental protocol during the
Mobilization phase.
- Patients who have failed previous collection attempt within 7 days or less from
randomization.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
Outcome Measure:
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.
Outcome Time Frame:
after last apheresis
Safety Issue:
No
Principal Investigator
Medical Monitor
Investigator Role:
Study Director
Investigator Affiliation:
Genzyme
Authority:
Germany: Federal Institute for Drugs and Medical Devices
Study ID:
AMD3100-EU23
NCT ID:
NCT00665314
Start Date:
November 2007
Completion Date:
June 2009
Related Keywords:
- Lymphoma
- Non Hodgkin's Lymphoma
- Hodgkin's Disease
- Multiple Myeloma
- Mobilisation stem cells
- G-CSF Mobilisation Regimen
- Lymphoma
- Multiple Myeloma
- Adult patients with lymphoma (Non Hodgkin's Lymphoma, Hodgkin's Disease) or Multiple Myeloma who previously failed Stem Cell Collections or Collection attempts.
- Hodgkin Disease
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
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