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

NCT02353572 | Terminated Phase 1 Results DMC

• 1 other identifier: 08-0817.cc
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Plasma Cell Myeloma; Plasmacytosis; Recurrent Plasma Cell Myeloma; Smoldering Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• 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%.

  100 days

Study Arms (1)

Melphalan, Bortezomib, Autologous transplant

EXPERIMENTAL

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; Drug: Bortezomib; Drug: Dexamethasone; Procedure: Autologous Transplant

Interventions

Melphalan DRUG

Given IV

Also known as: Alkeran

Melphalan, Bortezomib, Autologous transplant

Bortezomib DRUG

Given IV

Also known as: Velcade

Melphalan, Bortezomib, Autologous transplant

Dexamethasone DRUG

Given IV

Also known as: Decadron, Ozurdex, Maxidex, Baycadron

Melphalan, Bortezomib, Autologous transplant

Autologous Transplant PROCEDURE

Undergo autologous hematopoietic stem cell transplant

Also known as: Autologous Hematopoietic Stem Cell Transplantation

Melphalan, Bortezomib, Autologous transplant

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Smoldering Multiple Myeloma

Interventions

Melphalan; Bortezomib; Dexamethasone; Calcium Dobesilate; Transplantation, Autologous

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Hypergammaglobulinemia

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

This study was terminated due to the investigator's departure from the institution.

Results Point of Contact

• Title: Choon-kee Lee, MD
• Organization: University of Colorado

7208489252

Study Officials

• Choon-Kee Lee, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2015
• First Posted: February 2, 2015
• Study Start: November 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: March 9, 2015
• Results First Posted: March 9, 2015

Record last verified: 2015-01

Locations

US (1)