Combination High Dose Melphalan and Autologous Peripheral Blood Stem Cell (PBSC) Transplant With Bortezomib for Multiple Myeloma: A Dose and Schedule Finding Study

This study has been terminated.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Sagar Lonial, Emory University
ClinicalTrials.gov Identifier:
NCT00793650
First received: November 17, 2008
Last updated: August 17, 2012
Last verified: August 2012
  Purpose

The goal of this study is to evaluate the safety of melphalan and autologous PBSCT (peripheral blood stem cell transplantation - stem cells that come from your own body) in combination with bortezomib, a new FDA approved drug used to treat myeloma.


Condition Intervention Phase
Cancer
Multiple Myeloma
Drug: Bortezomib
Drug: Melphalan
Procedure: Autologous PBSC Transplant
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combination High Dose Melphalan and Autologous PBSC Transplant With Bortezomib for Multiple Myeloma: A Dose and Schedule Finding Study

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Safety and Engraftment [ Time Frame: Day 30 after transplant ] [ Designated as safety issue: Yes ]
    Peripheral blood progenitor cells were collected with either chemo-mobilization (27 of 39, 69%) or growth factor mobilization (12 of 39, 31%). Patients received an average of 9.0 × 10^6/kg CD34+ cells (range, 2.3-65) as their transplant graft.


Secondary Outcome Measures:
  • Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant. [ Time Frame: 100 days after transplant ] [ Designated as safety issue: No ]

    CR :Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow.

    VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24 hour.

    Partial Response:>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200mg per 24 hour.



Enrollment: 39
Study Start Date: May 2005
Study Completion Date: September 2011
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bortezomib before Melphalan
Enrolled patients were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m2) 24 hours before melphalan.
Drug: Bortezomib
Escalating doses of bortezomib 1.0, 1.3, or 1.6 mg/m2 in Arm A and Arm B.
Other Name: Bortezomib or Velcade
Drug: Melphalan

All patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2.

Other Name: Bortezomib or Velcade
Procedure: Autologous PBSC Transplant
Day 0 consists of the stem cell infusion.
Active Comparator: Bortezomib after Melphalan
Enrolled patients were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m2) 24 hours after melphalan.
Drug: Bortezomib
Escalating doses of bortezomib 1.0, 1.3, or 1.6 mg/m2 in Arm A and Arm B.
Other Name: Bortezomib or Velcade
Drug: Melphalan

All patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2.

Other Name: Bortezomib or Velcade
Procedure: Autologous PBSC Transplant
Day 0 consists of the stem cell infusion.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with multiple myeloma who are eligible for an autologous peripheral blood progenitor transplant
  • Male and female subjects between the age of 18 and 70 years.
  • Patient has given informed consent prior to any study related procedures with the knowledge that consent can be withdrawn at anytime without prejudice to future medical care
  • Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
  • Male subjects agrees to use an acceptable method for contraception for the duration of the study.
  • Biopsy proven diagnosis of multiple myeloma from bone marrow aspirate and biopsy prior to study initiation
  • Patient has achieved less than 90% disease reduction from previous treatment prior to transplant (as measured by serum or urine protein electrophoresis) and has more than 5% plasma cells in the bone marrow, or patient has progressed and has more than 5% plasma cells in the bone marrow.
  • Karnofsky Performance Status score of ≥ 60%
  • Patient has met the following laboratory requirements prior to Day -4
  • Platelet count ≥ 50, 000/mm3
  • Absolute Neutrophil Count ≥ 500/mm3
  • Hemoglobin ≥ 10 g/dL (transfusion allowed to meet this criterion)
  • Calculated creatinine clearance ≥ 30mL/min
  • Toxic effects of previous therapy or surgery resolved to Grade 2 or better

Exclusion Criteria:

  • Unsupportable anemia with < 10b/dL
  • Patient has a calculated or measured creatinine clearance of < 30mL/min within 14 days before enrollment
  • Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment
  • Patient has hypersensitivity to bortezomib, boron or mannitol
  • Patient has had an allergic reaction to melphalan or chlorambucil
  • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  • Patient has received other investigational drugs with 14 days before enrollment
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Cardiac or pulmonary dysfunction such that patients do not meet institutional pre-transplant evaluation criteria
  • Known central nervous system involvement or suspicion of involvement with Myeloma
  • Other active malignancies (with the exception of basal and squamous cell skin cancer) within 5 years of study entry. Patients with treated prostate or cervical cancer in situ who are 2 or more years from therapy and remain free of disease may be entered into the study at the investigator's discretion.
  • Known to be HIV positive, HIV-1 positive
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00793650

Locations
United States, Georgia
Emory University Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Sagar Lonial, MD Emory University Winship Cancer Institute
  More Information

No publications provided

Responsible Party: Sagar Lonial, MD, Emory University
ClinicalTrials.gov Identifier: NCT00793650     History of Changes
Other Study ID Numbers: 080-2005
Study First Received: November 17, 2008
Results First Received: March 14, 2012
Last Updated: August 17, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Cancer
Multiple Myeloma
Peripheral Blood Stem Cell Transplant

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bortezomib
Melphalan
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014