Melphalan+Bortezomib as a Conditioning Regimen for Autologous and Allogeneic Stem Cell Transplants in Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by H. Lee Moffitt Cancer Center and Research Institute
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00948922
First received: July 28, 2009
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to evaluate the effectiveness of Bortezomib when added to standard chemotherapy medicine(s) for treatment of Multiple Myeloma.


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib
Drug: Melphalan
Procedure: Autologous Stem Cell Transplant
Drug: Fludarabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Melphalan+Bortezomib as a Conditioning Regimen for Autologous and Allogeneic Stem Cell Transplants in Multiple Myeloma After Cytoreductive Therapy

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Progression Free Survival (PFS) - Allogeneic Stem Cell Transplant in Multiple Myeloma Arm [ Time Frame: 2 years ] [ Designated as safety issue: No ]

    PFS with allogeneic stem cell transplant using melphalan+fludarabine+bortezomib as the conditioning regimen. Survival time will be measured from the date of transplant to the date of progression, death or the last follow-up, whichever comes first.

    Progressive Disease (PD): Increase of ≥ 25% from lowest response value in any one or more of the following:

    Serum M-component and/or

    Urine M-component and/or

    Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL.

    Bone marrow plasma cell percentage; absolute percentage ≥ 10%

    Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas.

    Development of hypercalcaemia that can be attributed solely to the plasma cell proliferative disorder.


  • Progression Free Survival (PFS) - Autologous Stem Cell Transplant in Multiple Myeloma Arm [ Time Frame: 2 years ] [ Designated as safety issue: No ]

    PFS with autologous stem cell transplant in multiple myeloma using melphalan+bortezomib as the conditioning regimen. Survival time will be measured from the date of transplant to the date of progression, death or the last follow-up, whichever comes first.

    Progressive Disease (PD): Increase of ≥ 25% from lowest response value in any one or more of the following:

    Serum M-component and/or

    Urine M-component and/or

    Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved free light chain (FLC) levels. The absolute increase must be > 10 mg/dL.

    Bone marrow plasma cell percentage; absolute percentage ≥ 10%

    Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas.

    Development of hypercalcaemia that can be attributed solely to the plasma cell proliferative disorder.



Secondary Outcome Measures:
  • Overall Regimen Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Toxicity will be assessed according to Common Toxicity Criteria for Adverse Effects (CTCAE) 4.0 criteria and any grade 4 non-hematological toxicity up to 100 days will be recorded in all patients.

  • Overall Survival (OS) Rate [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Overall survival in patients with multiple myeloma treated with Bortezomib (Velcade®) containing conditioning regimen and autologous as well as allogeneic transplantation.

  • Molecular Complete Response (CR) Rates in Patients with Multiple Myeloma [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Complete Response according to International Myeloma Working Group uniform response criteria. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow.


Estimated Enrollment: 150
Study Start Date: June 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Autolgous Stem Cell Transplant Drug: Bortezomib
Day -3 bortezomib (1.3 mg/m2) as an intravenous push over 3 to 5 seconds (follows Melphalan infusion)
Other Name: Velcade
Drug: Melphalan
Day -4 and Day -3 Melphalan 100 mg/m2/day IV over 30 minutes
Other Name: Alkeran(R)
Procedure: Autologous Stem Cell Transplant
Day 0 Infusion of autologous stem cells
Allogeneic Stem Cell Transplant Drug: Bortezomib
Day -3 bortezomib (1.3 mg/m2) as an intravenous push over 3 to 5 seconds (follows fludarabine and melphalan infusion)
Other Name: Velcade
Drug: Fludarabine
Days -6,-5,-4,-3 Fludarabine 30 mg/m2/day IV
Other Name: Fludara(R)
Drug: Melphalan
Day -4, Day -3 Melphalan 70 mg/m2/day IV over 30 minutes
Other Name: Alkeran(R)

Detailed Description:

The primary objectives of this study are:

  • To determine the 2 year-progression free survival in multiple myeloma with an allogeneic transplant using a conditioning regimen of melphalan + fludarabine + Bortezomib in patients < 60 years of age and available HLA-matched donor and compare it with the 2 year-progression-free-survival after an autologous stem cell transplant with melphalan+Bortezomib conditioning in patients < 60 years.
  • To determine the 2 year-progression free survival in multiple myeloma with an autologous stem cell transplant using a conditioning regimen of melphalan + Bortezomib. for patients > 60 years of age and patients < 60 years of age who decline allogeneic stem cell transplant.

The secondary objectives of this study are:

  • To determine the overall survival in multiple myeloma with autologous or allogeneic stem cell transplants using the above conditioning regimens
  • To determine the response rates in multiple myeloma using the above regimens.
  • To determine minimal residual disease status using allele specific oligonucleotides (ASO-PCR) by PCR and flow-cytometry for multiple myeloma cells.
  • To correlate minimal residual disease status with 2 year progression free survival and overall survival.
  • To determine the incidence of acute and chronic graft-versus-host disease (GVHD) in multiple myeloma with allogeneic stem cell transplant using the above conditioning regimen.
  • To examine quality of life in patients treated with allogeneic and autologous stem cell transplants using the above conditioning regimen.
  Eligibility

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

Inclusion Criteria:

Multiple Myeloma Criteria(International Uniform Response Criteria for Multiple Myeloma)

  • Patients with responsive disease after any line of induction therapy
  • A complete response
  • A very good partial response
  • A partial response
  • Patients greater than or equal to 18 years of age are eligible. There is upper age limit of 60 years for allogeneic transplants.
  • Patients must have a histologically confirmed diagnosis.
  • All patients should have a life expectancy of at least 12 weeks.
  • Patients must have undergone a complete psychosocial evaluation and have been considered capable of compliance.
  • Meet the following criteria for allogeneic hematopoietic cell transplant:
  • Must have an identified donor match defined as: HLA-A, HLA-B, HLA- C, DRB1 8/8 allele matched sibling, family member, or unrelated donor. [7/8 would go on separate mismatched trials] and be < 60 years of age.
  • Calculated hematopoietic cell transplantation-specific comorbidity index (HCT-CI) <3

Exclusion Criteria:

  • Patients who do not achieve at least a partial response (PR) by the criteria mentioned above with induction therapy.
  • Patient has a platelet count of <30 x 10^9/L within 14 days before enrollment.
  • Patient has >/= Grade 2 peripheral neuropathy within 14 days before enrollment.
  • Patient has an absolute neutrophil count of <1.0 x 10^9/L within 14 days before enrollment.
  • Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant in order for the subject to be considered eligible. Left ventricular ejection fraction (LVEF) by multiple gated acquisition (MUGA) scan < 40%.
  • Patient has hypersensitivity to bortezomib, boron or mannitol.
  • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-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.
  • Patients with a diffusing capacity of lung for carbon monoxide (DLCO) less than 50% (adjusted) of normal or with symptomatic obstructive or restrictive lung disease are ineligible.
  • Patients with a total bilirubin greater than 2.0 mg/dL excluding Gilbert's syndrome and serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) greater than two and a half times normal (unless due to primary malignancy), or a history of severe hepatic dysfunction are ineligible.
  • Calculated creatinine clearance </= 30 ml/min within 14 days before enrollment
  • Patients with active infections are ineligible.
  • Patients who are HIV positive are ineligible.
  • Patients with active leptomeningeal involvement are ineligible. Patients with a history of previous cerebrospinal fluid (CSF) tumor involvement without symptoms or signs are eligible provided the CSF is now free of disease on lumbar puncture, and MRI of the brain shows no tumor involvement. Patients with severe symptomatic central nervous system (CNS) disease of any etiology are ineligible.
  • Patients with uncontrolled insulin-dependent diabetes mellitus or uncompensated major thyroid or adrenal dysfunction are ineligible.
  • Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of >/= 2(Karnofsky < 50%) are ineligible.
  • Patients with an ECOG performance status of 2 to 3(Karnofsky 30-50%), secondary to bone pain, may be enrolled.
  • Patients with an ECOG performance status of 2 to 3(Karnofsky 30-50%), secondary to a potentially reversible disease-related problem, may be enrolled.
  • Patients with any previous malignancy other than non-melanoma skin cancer are ineligible, unless the patient is without evidence of disease >/= 5 years after the treatment for the cancer was completed.
  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: NCT00948922

Contacts
Contact: Chiaka Nwoga 813-745-6779 chiaka.nwoga@moffitt.org

Locations
United States, Florida
H. Lee Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Chiaka Nwoga    813-745-6779    chiaka.nwoga@moffitt.org   
Principal Investigator: Melissa Alsina, MD         
Sub-Investigator: Claudio Anasetti, MD         
Sub-Investigator: Ernesto Ayala, MD         
Sub-Investigator: Rachid Baz, MD         
Sub-Investigator: Hugo Fernandez, MD         
Sub-Investigator: Teresa Field, MD, PhD         
Sub-Investigator: William Janssen, PhD         
Sub-Investigator: Heather Jim, PhD         
Sub-Investigator: Lynn Moscinski, MD         
Sub-Investigator: Lia Perez, MD         
Sub-Investigator: Daniel Sullivan, MD         
Sub-Investigator: Marcie Riches, MD, MS         
Sub-Investigator: Joseph Pidala, MD         
Sub-Investigator: Taiga Nishihori, MD         
Sub-Investigator: Frederick Locke, MD         
Sub-Investigator: Jose Leonel Ochoa-Bayona, MD         
Sub-Investigator: Brian Betts, MD         
Sub-Investigator: Kenneth Shain, MD, PhD         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Melissa Alsina, MD H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00948922     History of Changes
Other Study ID Numbers: MCC-15697, XO5271
Study First Received: July 28, 2009
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
multiple myeloma
myeloma
myeloma proteins
autologous
allogeneic

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
Melphalan
Fludarabine
Fludarabine monophosphate
Bortezomib
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 26, 2014