Trial of Three Stem Cell Mobilization Regimens for Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT01146834
- Lead Sponsor
- Weill Medical College of Cornell University
- Brief Summary
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 Arm D = PLERIXAFOR \& G-CSF Arm E = PLERIXAFOR, VELCADE, \& G-CSF
- Detailed Description
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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 47
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Voluntary written informed consent
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Confirmed diagnosis of multiple myeloma
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Age > than 18 years at the time of signing the informed consent form.
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Karnofsky performance status above 60%
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Patients must be within 30 days of completing induction therapy.
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Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control .
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Male subject agrees to use an acceptable method for contraception for the duration of the study.
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Life expectancy > 12 weeks.
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Subjects must have a MUGA scan or echo with LVEF >50%
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Subjects must meet the following laboratory parameters:
- Absolute neutrophil count (ANC) ≥1500 cells/mm3
- Platelets count ≥ 50,000/mm3
- Hemoglobin > 9.0 g/dL
- Serum SGOT/AST <3.0 x upper limits of normal (ULN)
- Serum SGPT/ALT <3.0 x upper limits of normal (ULN)
- Serum creatinine < 2.5 mg/dL or creatinine clearance > 40ml/min
- Serum total bilirubin < 1.5 x ULN
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: VELCADE, CYCLOPHOSPHAMIDE, & G-CSF bortezomib (Velcade) 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. Arm B: VELCADE & G-CSF bortezomib (Velcade) 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 Arm E: PLERIXAFOR, VELCADE, & G-CSF bortezomib (Velcade) Bortezomib at 1.3 mg/m2 IVP on days 1, 4, 8 and 11. G-CSF is given for ten (+/- wo) consecutive days starting on day 9 at a dose of 10 micrograms/kg/day. Plerixafor is given on day 12, approximately 11 hours prior to stem cell collection attempt and is continued daily until collection is complete. Pheresis will commence for everyone on Day 13 regardless of ANC status. Arm A: VELCADE, CYCLOPHOSPHAMIDE, & G-CSF cyclophosphamide 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. Arm A: VELCADE, CYCLOPHOSPHAMIDE, & G-CSF G-CSF 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. Arm B: VELCADE & G-CSF G-CSF 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 Arm C: CYCLOPHOSPHAMIDE & G-CSF G-CSF 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. Arm D: PLERIXAFOR & G-CSF Plerixafor G-CSF is given for ten (+/- two) consecutive days starting on day 1 at a dose of 10 micrograms/kg/day. Plerixafor is given on day 4, approximately 11 hours prior to stem cell collection attempt on Day 5. Both G-CSF and plerixafor are continued daily until collection is complete. Pheresis will commence for everyone on Day 5 regardless of ANC status. Arm C: CYCLOPHOSPHAMIDE & G-CSF cyclophosphamide 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. Arm D: PLERIXAFOR & G-CSF G-CSF G-CSF is given for ten (+/- two) consecutive days starting on day 1 at a dose of 10 micrograms/kg/day. Plerixafor is given on day 4, approximately 11 hours prior to stem cell collection attempt on Day 5. Both G-CSF and plerixafor are continued daily until collection is complete. Pheresis will commence for everyone on Day 5 regardless of ANC status. Arm E: PLERIXAFOR, VELCADE, & G-CSF G-CSF Bortezomib at 1.3 mg/m2 IVP on days 1, 4, 8 and 11. G-CSF is given for ten (+/- wo) consecutive days starting on day 9 at a dose of 10 micrograms/kg/day. Plerixafor is given on day 12, approximately 11 hours prior to stem cell collection attempt and is continued daily until collection is complete. Pheresis will commence for everyone on Day 13 regardless of ANC status. Arm E: PLERIXAFOR, VELCADE, & G-CSF Plerixafor Bortezomib at 1.3 mg/m2 IVP on days 1, 4, 8 and 11. G-CSF is given for ten (+/- wo) consecutive days starting on day 9 at a dose of 10 micrograms/kg/day. Plerixafor is given on day 12, approximately 11 hours prior to stem cell collection attempt and is continued daily until collection is complete. Pheresis will commence for everyone on Day 13 regardless of ANC status.
- Primary Outcome Measures
Name Time Method Number of Patients Able to Collect >=6 x 106 CD34+ Cells/kg in <= 2 Collections. 36 months The primary endpoint in all five treatment arms is the percentage of patients who are able to achieve greater than 6 x 106 CD34+ stems cells/kg harvested (defined as effectiveness). Note that no patients were enrolled Arm D and Arm E.
- Secondary Outcome Measures
Name Time Method Number of Patients Who Achieved Neutrophil Recovery After Melphalan 200 Based Transplant 20 days post-transplant Number of patients who achieved neutrophil recovery after Melphalan 200 based transplant in 20 days or fewer. Neutrophil recovery is defined as an absolute neutrophil count of greater than 0.5 k/uL for three consecutive days.
Number of Patients Who Achieved Platelet Recovery After Melphalan 200 Based Transplant 20 days post-transplant Number of patients who achieved platelet recovery after Melphalan 200 based transplant in 20 days or fewer. Platelet recovery is defined as a platelet count of greater than 20,000, untransfused, for three consecutive days.
Trial Locations
- Locations (5)
Memorial Sloan-Kettering Cancer Center):
🇺🇸New York, New York, United States
Emory University
🇺🇸Atlanta, Georgia, United States
New York University Cancer Institute
🇺🇸New York, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Columbia Presbyterian Medical Center):
🇺🇸New York, New York, United States