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).

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.