Trial of Three Stem Cell Mobilization Regimens for Multiple Myeloma

This phase III randomized trial compares three different peripheral stem cell mobilization regimens for patients with multiple myeloma who have received primary induction therapy or other therapies. Up to 180 patients will be enrolled. Patients eligible for treatment will be randomized to one of the three following mobilization regimens:

Arm A = VELCADE, CYCLOPHOSPHAMIDE, G-CSF Arm B = VELCADE & G-CSF Arm C = CYCLOPHOSPHAMIDE & G-CSF

PRIMARY STUDY OBJECTIVES

• To compare the efficacy of the following peripheral stem cell mobilization regimens for MM: i. High dose cyclophosphamide, VELCADE, and G-CSF ii. VELCADE and G-CSF iii. High dose cyclophosphamide and G-CSF

SECONDARY STUDY OBJECTIVES

• To evaluate biomarkers as surrogate markers of mobilization in each arm To evaluate changes in tumor mass as defined by standard response parameters. To evaluate the safety of each of the arms.

This phase III randomized trial compares three different peripheral stem cell mobilization regimens for patients with multiple myeloma who have received primary induction therapy

Primary Endpoints

a) Percentage of patients able to collect >6 x 106 CD34+ cells/kg in < 2 collections.

Secondary Endpoints

1. Engrafting: Neutrophil recovery (ANC >0.5 of <12 days), Plt recovery (>20K untransfused <20 days)) after mel 200 based transplant.
2. Toxicities

• Drug: bortezomib (Velcade)
  1.3 mg/m2 IVP on days 1, 4, 8 and 11
  Other Name: Velcade
• Drug: cyclophosphamide
  2.0 g/m2 (day 4 for Arm A and day 1 for Arm C)
  Other Name: Cytoxan
• Drug: G-CSF
  given for ten (+/- two) consecutive days starting on day 9 at a dose of 10 micrograms/kg/day (start on day 2 for Arm C)
  Other Names:

  • Filgrastim
  • Neupogen

• Experimental: Arm A
  VELCADE at 1.3 mg/m2 IVP on days 1, 4, 8 and 11 in combination with high-dose cyclophosphamide at 2.0 g/m2 on day 4. G-CSF is given for ten (+/- two) consecutive days starting on day 9 at a dose of 10 micrograms/kg/day. Pheresis will commence once ANC of 1.5 is reached.
  Interventions:

  • Drug: bortezomib (Velcade)
  • Drug: cyclophosphamide
  • Drug: G-CSF
• Experimental: Arm B
  VELCADE at 1.3 mg/m2 IVP on days 1, 4, 8 and 11. G-CSF is given for ten (+/- two) consecutive days starting on day 9 at a dose of 10 micrograms/kg/day. Day 12 start pheresis collection
  Interventions:

  • Drug: bortezomib (Velcade)
  • Drug: G-CSF
• Experimental: Arm C
  High-dose cyclophosphamide at 2.0 g/m2 on day 1. G-CSF is given for ten (+/- two) consecutive days starting on day 2 at a dose of 10 micrograms/kg/day. Pheresis will commence once ANC of 1.5 is reached.
  Interventions:

  • Drug: cyclophosphamide
  • Drug: G-CSF

Inclusion Criteria:

• Voluntary written informed consent
• Confirmed diagnosis of multiple myeloma
• Age > than 18 years at the time of signing the informed consent form.
• Karnofsky performance status > = 70%
• Patients must be within 30 days of completing induction therapy.
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control .
• Male subject agrees to use an acceptable method for contraception for the duration of the study.
• Life expectancy > 12 weeks.
• Subjects must have a MUGA scan or echo with LVEF >50%

• Subjects must meet the following laboratory parameters:

  1. Absolute neutrophil count (ANC) ≥1500 cells/mm3
  2. Platelets count ≥ 50,000/mm3
  3. Hemoglobin > 9.0 g/dL
  4. Serum SGOT/AST <3.0 x upper limits of normal (ULN)
  5. Serum SGPT/ALT <3.0 x upper limits of normal (ULN)
  6. Serum creatinine < 2.5 mg/dL or creatinine clearance > 40ml/min
  7. Serum total bilirubin < 1.5 x ULN

Exclusion Criteria:

• Patients with (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine) unless measurable disease is available with imaging techniques such as MRI and PET scan.
• History of allergic reactions to compounds containing boron, mannitol, VELCADE
• Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for > = 5 years.
• NYHA Class III or IV heart disease. History of active unstable angina, congestive heart disease, severe uncontrolled cardiac arrhythmia, electrocardiographic evidence of acute ischemia, active conduction system abnormalities or myocardial infarction within 6 months prior to enrollment. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Female patients who are pregnant or breastfeeding. Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
• Known HIV or hepatitis A, B, or C positivity---ONLY IF ACTIVE
• Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
• Any concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk
• Patient has > = Grade 2 peripheral neuropathy within 14 days before enrollment.
• Patient has received other investigational drugs with 14 days before enrollment
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.