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Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma

Primary Purpose

Plasma Cell Myeloma, Plasmacytosis, Recurrent Plasma Cell Myeloma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Melphalan
Bortezomib
Dexamethasone
Autologous Transplant
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Plasma Cell Myeloma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with symptomatic active multiple myeloma requiring treatment, including those whose prior smoldering myeloma progressed to symptomatic disease requiring chemotherapy; both newly diagnosed and previously treated patients are eligible for the study
  • Presence of quantifiable M-component of immunoglobulin G (IgG), IgA, IgD, or IgE and/or urinary kappa or lambda light chain or Bence Jones protein, in order to evaluate response; non-secretory patients are eligible provided the patient has > 20% plasmacytosis or multiple (> 3) focal plasmacytomas on magnetic resonance imaging (MRI) or diffuse hyperintense signal on short tau inversion recovery (STIR) weighted images
  • Performance status of 0-2 based on Southwest Oncology Group (SWOG) criteria; patients with a poor performance status (3-4) are also eligible after having improved their performance to 0-2
  • No significant co-morbid medical conditions; no uncontrolled life threatening infection
  • Patient evaluation should be done within 35 days prior to registration; signed informed consent should be obtained from all patients in accordance with institutional and federal guidelines

Exclusion Criteria:

  • Patients with a history of recent (< 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, difficult to control significant cardiac arrhythmias, or arrhythmia associated with prolonged QT interval; left ventricular ejection fraction by echocardiogram or multi gated acquisition scan (MUGA) < 45% assessed within 35 days prior to study registration
  • Patients with a history of moderate to severe chronic obstructive and/or restrictive pulmonary disease, with a forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 50% of the predicted values; diffusing capacity of the lung for carbon monoxide (DLCO) < 50%; partial pressure of oxygen (P02) < 70 mmHg
  • Patients with a prior history of malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for at least three years
  • Pregnant or nursing women; women of child-bearing potential must have a negative pregnancy documented within one week of registration; women/men of reproductive potential may not participate unless they have agreed to use two forms of effective contraceptive method
  • Human immunodeficiency virus (HIV) positive patients
  • Transaminases > 2 x normal values or bilirubin > 2 x normal values; prior history of chronic liver disease
  • Patients with renal failure on dialysis
  • Active uncontrolled infection
  • History of significant psychiatric illness

Sites / Locations

  • University of Colorado Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Melphalan, Bortezomib, Autologous transplant

Arm Description

Patients receive melphalan IV continuously on days -5 to -2 and bortezomib IV over 3-5 seconds on days -4 and -1. Patients also receive dexamethasone IV on day -1 prior to the second dose of bortezomib. Beginning two days after completion of melphalan infusion, patients undergo autologous hematopoietic stem cell transplant. Eligible patients may undergo a second transplant 2-4 months after completion of the first transplant.

Outcomes

Primary Outcome Measures

Maximally Tolerable Dose (MTD) of Both Melphalan and Bortezomib as Combination
MTD is defined as one dose below that which 33% of patients within cohort experienced dose limiting toxicity. Unacceptable toxicity is defined as intractable veno-occlusive disorder, new onset of renal failure requiring dialysis, acute heart failure of New York Heart Association class III/IV, or interstitial pneumonia requiring ventilator management for longer than 3 days or grade 4 neuropathy. A 100-day mortality/toxicity rate of 3% or more is considered unacceptable. Will consider as evidence an observed 100-day mortality/toxicity rate whose lower one-sided 90% confidence bound exceeds 3%.

Secondary Outcome Measures

Full Information

First Posted
January 28, 2015
Last Updated
February 23, 2015
Sponsor
University of Colorado, Denver
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1. Study Identification

Unique Protocol Identification Number
NCT02353572
Brief Title
Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma
Official Title
A Phase I-II Study of Infusional Melphalan + Bortezomib for Myeloablative Therapy Prior to Autologous Transplant for Patients With Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Terminated
Why Stopped
Principle investigator left the institution
Study Start Date
November 2009 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase I/II trial studies the safety and best dose of melphalan and bortezomib when given prior to an autologous stem cell transplant and to see how well they work in treating patients with multiple myeloma. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bortezomib may help melphalan work better by making cancer cells more sensitive to the drug. Giving chemotherapy before an autologous hematopoietic stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving melphalan together with bortezomib prior to autologous hematopoietic stem cell transplant may be a better treatment for multiple myeloma.
Detailed Description
This is a phase I, dose-escalation study of melphalan and bortezomib followed by a phase II study. Patients receive melphalan intravenously (IV) continuously on days -5 to -2 and bortezomib IV over 3-5 seconds on days -4 and -1. Patients also receive dexamethasone IV on day -1 prior to the second dose of bortezomib. Beginning two days after completion of melphalan infusion, patients undergo autologous hematopoietic stem cell transplant. Eligible patients may undergo a second transplant 2-4 months after completion of the first transplant. After completion of study treatment, patients are followed up monthly for at least 1 year and then every 3-6 months thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plasma Cell Myeloma, Plasmacytosis, Recurrent Plasma Cell Myeloma, Smoldering Plasma Cell Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Melphalan, Bortezomib, Autologous transplant
Arm Type
Experimental
Arm Description
Patients receive melphalan IV continuously on days -5 to -2 and bortezomib IV over 3-5 seconds on days -4 and -1. Patients also receive dexamethasone IV on day -1 prior to the second dose of bortezomib. Beginning two days after completion of melphalan infusion, patients undergo autologous hematopoietic stem cell transplant. Eligible patients may undergo a second transplant 2-4 months after completion of the first transplant.
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alkeran
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Decadron, Ozurdex, Maxidex, Baycadron
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Autologous Transplant
Other Intervention Name(s)
Autologous Hematopoietic Stem Cell Transplantation
Intervention Description
Undergo autologous hematopoietic stem cell transplant
Primary Outcome Measure Information:
Title
Maximally Tolerable Dose (MTD) of Both Melphalan and Bortezomib as Combination
Description
MTD is defined as one dose below that which 33% of patients within cohort experienced dose limiting toxicity. Unacceptable toxicity is defined as intractable veno-occlusive disorder, new onset of renal failure requiring dialysis, acute heart failure of New York Heart Association class III/IV, or interstitial pneumonia requiring ventilator management for longer than 3 days or grade 4 neuropathy. A 100-day mortality/toxicity rate of 3% or more is considered unacceptable. Will consider as evidence an observed 100-day mortality/toxicity rate whose lower one-sided 90% confidence bound exceeds 3%.
Time Frame
100 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with symptomatic active multiple myeloma requiring treatment, including those whose prior smoldering myeloma progressed to symptomatic disease requiring chemotherapy; both newly diagnosed and previously treated patients are eligible for the study Presence of quantifiable M-component of immunoglobulin G (IgG), IgA, IgD, or IgE and/or urinary kappa or lambda light chain or Bence Jones protein, in order to evaluate response; non-secretory patients are eligible provided the patient has > 20% plasmacytosis or multiple (> 3) focal plasmacytomas on magnetic resonance imaging (MRI) or diffuse hyperintense signal on short tau inversion recovery (STIR) weighted images Performance status of 0-2 based on Southwest Oncology Group (SWOG) criteria; patients with a poor performance status (3-4) are also eligible after having improved their performance to 0-2 No significant co-morbid medical conditions; no uncontrolled life threatening infection Patient evaluation should be done within 35 days prior to registration; signed informed consent should be obtained from all patients in accordance with institutional and federal guidelines Exclusion Criteria: Patients with a history of recent (< 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, difficult to control significant cardiac arrhythmias, or arrhythmia associated with prolonged QT interval; left ventricular ejection fraction by echocardiogram or multi gated acquisition scan (MUGA) < 45% assessed within 35 days prior to study registration Patients with a history of moderate to severe chronic obstructive and/or restrictive pulmonary disease, with a forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 50% of the predicted values; diffusing capacity of the lung for carbon monoxide (DLCO) < 50%; partial pressure of oxygen (P02) < 70 mmHg Patients with a prior history of malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for at least three years Pregnant or nursing women; women of child-bearing potential must have a negative pregnancy documented within one week of registration; women/men of reproductive potential may not participate unless they have agreed to use two forms of effective contraceptive method Human immunodeficiency virus (HIV) positive patients Transaminases > 2 x normal values or bilirubin > 2 x normal values; prior history of chronic liver disease Patients with renal failure on dialysis Active uncontrolled infection History of significant psychiatric illness
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Choon-Kee Lee, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

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Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma

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