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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02353572
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arm: 1
• Duration (Months): 22
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Plasma Cell Myeloma; Plasmacytosis; Recurrent Plasma Cell Myeloma; Smoldering Plasma Cell Myeloma	Drug: Melphalan; Drug: Bortezomib; Drug: Dexamethasone; Procedure: Autologous Transplant	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I-II Study of Infusional Melphalan + Bortezomib for Myeloablative Therapy Prior to Autologous Transplant for Patients With Multiple Myeloma
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

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: Bortezomib; Given IV; Other Names: Velcade ; Drug: Dexamethasone; Given IV; Other Names: Decadron, Ozurdex, Maxidex, Baycadron ; Procedure: Autologous Transplant; Undergo autologous hematopoietic stem cell transplant; Other Names: Autologous Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcome Measures

1. Maximally Tolerable Dose (MTD) of Both Melphalan and Bortezomib as Combination [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%.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Cancer Center	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

• Principal Investigator: Choon-Kee Lee, MD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02353572
• Other Study ID Numbers: 08-0817.cc
• First Posted: Feb 2, 2015
• Last Update Posted: Mar 9, 2015
• Last Verified: Jan 1, 2015

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Dexamethasone; Bortezomib; Melphalan

Study Results

Participant Flow

Recruitment Details	Between November 2009 and September 2011, 3 patients were enrolled in the study from University of Colorado Cancer Center
Pre-assignment Detail	Within 35 days of planned therapy, patients were evaluated for eligibility by standard tests: paraprotein assessment, bone marrow biopsy and aspiration, MRI scan, PET/CT scan, echocardiography and pulmonary function test. Patients who were not be able to pursue the tandem autotransplant were eligible for one autotransplant.

Arm/Group Title	Melphalan, Bortezomib, Autologous Transplant
Arm/Group Description	Patients received melphalan IV continuously on days -5 to -2 and bortezomib IV over 3-5 seconds on days -4 and -1. Patients also received dexamethasone IV on day -1 prior to the second dose of bortezomib. Beginning two days after completion of melphalan infusion, patients underwent autologous hematopoietic stem cell transplant.
Period Title: Overall Study
STARTED	3
COMPLETED	0
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Melphalan, Bortezomib, Autologous Transplant
Arm/Group Description	Patients received melphalan IV continuously on days -5 to -2 and bortezomib IV over 3-5 seconds on days -4 and -1. Patients also received dexamethasone IV on day -1 prior to the second dose of bortezomib. Beginning two days after completion of melphalan infusion, patients underwent autologous hematopoietic stem cell transplant.
Overall Participants	3
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 66.7%
>=65 years	1 33.3%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.3 (5.0)
Sex: Female, Male (Count of Participants)
Female	1 33.3%
Male	2 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 66.7%
White	1 33.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The study was terminated, study endpoints were not reached.

Arm/Group Title	Melphalan, Bortezomib, Autologous Transplant
Arm/Group Description	Patients received melphalan IV continuously on days -5 to -2 and bortezomib IV over 3-5 seconds on days -4 and -1. Patients also received dexamethasone IV on day -1 prior to the second dose of bortezomib. Beginning two days after completion of melphalan infusion, patients underwent autologous hematopoietic stem cell transplant.
Measure Participants	0

Adverse Events

Time Frame	Patients were assessed for adverse events for approximately 1 year until the study was terminated.
Arm/Group Title	Melphalan, Bortezomib, Autologous Transplant
Arm/Group Description	Patients received melphalan IV continuously on days -5 to -2 and bortezomib IV over 3-5 seconds on days -4 and -1. Patients also received dexamethasone IV on day -1 prior to the second dose of bortezomib. Beginning two days after completion of melphalan infusion, patients underwent autologous hematopoietic stem cell transplant.
All Cause Mortality
	Melphalan, Bortezomib, Autologous Transplant
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Melphalan, Bortezomib, Autologous Transplant
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Other (Not Including Serious) Adverse Events
	Melphalan, Bortezomib, Autologous Transplant
	Affected / at Risk (%)	# Events
Total	0/3 (0%)

Limitations/Caveats

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

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.