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

February 23, 2015 updated by: University of Colorado, Denver

A Phase I-II Study of Infusional Melphalan + Bortezomib for Myeloablative Therapy Prior to Autologous Transplant for Patients With Multiple Myeloma

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Melphalan, Bortezomib, Autologous transplant
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.
Drug: Melphalan
Given IV
Other Names:
  • Alkeran
Drug: Dexamethasone
Given IV
Other Names:
  • Decadron, Ozurdex, Maxidex, Baycadron
Drug: Bortezomib
Given IV
Other Names:
  • Velcade
Procedure: Autologous Transplant
Undergo autologous hematopoietic stem cell transplant
Other Names:
  • Autologous Hematopoietic Stem Cell Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximally Tolerable Dose (MTD) of Both Melphalan and Bortezomib as Combination
Time Frame: 100 days
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%.
100 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2009

Primary Completion (ACTUAL)

September 1, 2011

Study Completion (ACTUAL)

September 1, 2011

Study Registration Dates

First Submitted

January 28, 2015

First Submitted That Met QC Criteria

January 28, 2015

First Posted (ESTIMATE)

February 2, 2015

Study Record Updates

Last Update Posted (ESTIMATE)

March 9, 2015

Last Update Submitted That Met QC Criteria

February 23, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-0817.cc

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Plasma Cell Myeloma

Clinical Trials on Melphalan

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bahamas

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe