Trial of Three Stem Cell Mobilization Regimens for Multiple Myeloma

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

Official Title
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A Prospective Randomized Trial Comparing Three Different Peripheral Stem Cell Mobilization Regimens in Patients With Symptomatic Multiple Myeloma or Lymphoma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: bortezomib (Velcade)
* Drug: cyclophosphamide
* Drug: G-CSF
* Drug: Plerixafor


Participation Criteria
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Eligibility Criteria
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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 above 60% 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: 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: VELCADE, CYCLOPHOSPHAMIDE, & G-CSF<br>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. | Drug: bortezomib (Velcade)<br>* 1.3 mg/m2 IVP on days 1, 4, 8 and 11<br>* Other names: Velcade;Drug: cyclophosphamide<br>* 2.0 g/m2 (day 4 for Arm A and day 1 for Arm C)<br>* Other names: Cytoxan;Drug: G-CSF<br>* 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 and start on Day 1 for Arm D)<br>* Other names: Neupogen;|
| Experimental: Arm B: VELCADE & G-CSF<br>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 | Drug: bortezomib (Velcade)<br>* 1.3 mg/m2 IVP on days 1, 4, 8 and 11<br>* Other names: Velcade;Drug: G-CSF<br>* 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 and start on Day 1 for Arm D)<br>* Other names: Neupogen;|
| Experimental: Arm C: CYCLOPHOSPHAMIDE & G-CSF<br>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. | Drug: cyclophosphamide<br>* 2.0 g/m2 (day 4 for Arm A and day 1 for Arm C)<br>* Other names: Cytoxan;Drug: G-CSF<br>* 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 and start on Day 1 for Arm D)<br>* Other names: Neupogen;|
| Experimental: Arm D: PLERIXAFOR & G-CSF<br>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. | Drug: G-CSF<br>* 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 and start on Day 1 for Arm D)<br>* Other names: Neupogen;Drug: Plerixafor<br>* plerixafor is given on day 4, approximately 11 hours prior to stem cell collection attempt on Day 5, plerixafor daily until stem cell collection is complete (Arm D), start on Day 12, approximately 11 hours prior to stem cell collection attempt and plerixafor daily until collection if complete (Arm E)<br>* Other names: Mozobil;|
| Experimental: Arm E: PLERIXAFOR, VELCADE, & G-CSF<br>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. | Drug: bortezomib (Velcade)<br>* 1.3 mg/m2 IVP on days 1, 4, 8 and 11<br>* Other names: Velcade;Drug: G-CSF<br>* 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 and start on Day 1 for Arm D)<br>* Other names: Neupogen;Drug: Plerixafor<br>* plerixafor is given on day 4, approximately 11 hours prior to stem cell collection attempt on Day 5, plerixafor daily until stem cell collection is complete (Arm D), start on Day 12, approximately 11 hours prior to stem cell collection attempt and plerixafor daily until collection if complete (Arm E)<br>* Other names: Mozobil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Able to Collect >=6 x 106 CD34+ Cells/kg in <= 2 Collections. | 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. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Achieved Neutrophil Recovery After Melphalan 200 Based 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. | 20 days post-transplant | 
| Number of Patients Who Achieved Platelet Recovery After Melphalan 200 Based 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. | 20 days post-transplant |