Trial of Three Stem Cell Mobilization Regimens for Multiple Myeloma

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

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

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: bortezomib (Velcade); Drug: cyclophosphamide; Drug: G-CSF; Drug: Plerixafor

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

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10016
      • New York University Cancer Institute
    • New York, New York, United States, 10032
      • Columbia Presbyterian Medical Center):
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center):

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: VELCADE, CYCLOPHOSPHAMIDE, & 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.	Drug: bortezomib (Velcade); 1.3 mg/m2 IVP on days 1, 4, 8 and 11; Other Names: Velcade; Drug: cyclophosphamide; 2.0 g/m2 (day 4 for Arm A and day 1 for Arm C); Other Names: 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 and start on Day 1 for Arm D); Other Names: Filgrastim; Neupogen
Experimental: Arm B: VELCADE & 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	Drug: bortezomib (Velcade); 1.3 mg/m2 IVP on days 1, 4, 8 and 11; Other Names: Velcade; 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 and start on Day 1 for Arm D); Other Names: Filgrastim; Neupogen
Experimental: Arm C: CYCLOPHOSPHAMIDE & 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.	Drug: cyclophosphamide; 2.0 g/m2 (day 4 for Arm A and day 1 for Arm C); Other Names: 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 and start on Day 1 for Arm D); Other Names: Filgrastim; Neupogen
Experimental: Arm D: PLERIXAFOR & 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.	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 and start on Day 1 for Arm D); Other Names: Filgrastim; Neupogen; Drug: Plerixafor; 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); Other Names: Mozobil
Experimental: Arm E: PLERIXAFOR, VELCADE, & 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.	Drug: bortezomib (Velcade); 1.3 mg/m2 IVP on days 1, 4, 8 and 11; Other Names: Velcade; 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 and start on Day 1 for Arm D); Other Names: Filgrastim; Neupogen; Drug: Plerixafor; 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); Other Names: Mozobil

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Millennium Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Ruben Niesvizky, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2011
• Primary Completion (Actual): February 4, 2019
• Study Completion (Actual): February 4, 2019

Study Registration Dates

• First Submitted: June 16, 2010
• First Submitted That Met QC Criteria: June 17, 2010
• First Posted (Estimate): June 22, 2010

Study Record Updates

• Last Update Posted (Actual): December 27, 2019
• Last Update Submitted That Met QC Criteria: December 18, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Bortezomib; Plerixafor
• Other Study ID Numbers: 1005011049; X05324 (Other Grant/Funding Number: Millennium)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No