Low-Dose Melphalan and Dexamethasone Compared With High-Dose Melphalan Followed By Autologous Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00477971
First received: May 23, 2007
Last updated: June 23, 2015
Last verified: June 2015
Results First Received: June 23, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Multiple Myeloma and Plasma Cell Neoplasm
Interventions: Biological: filgrastim
Drug: dexamethasone
Drug: melphalan
Procedure: autologous hematopoietic stem cell transplantation

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
From October 2005 to August 2012, 89 participants were recruited.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This study was originally designed as a randomized Phase III clinical trial; however the unwillingness of participants to be randomized to treatment led to changes. The protocol was amended to allow participants to choose between the two regimens.

Reporting Groups
  Description
Arm A Patients receive low-dose melphalan 20 mg/m^2 IV over 15-30 minutes on day 1 or 0.12 mg/kg tablet orally once daily on days 1-7 and dexamethasone 40 mg orally on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses. (Study treatment beyond one year is not allowed.)
Arm B Patients receive filgrastim (G-CSF) 10 mg/kg/day on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan 140 mg/m^2 IV for low risk or 200 mg/m^2 IV for high risk patients over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.

Participant Flow:   Overall Study
    Arm A     Arm B  
STARTED     34     55  
COMPLETED     17     49  
NOT COMPLETED     17     6  
Disease progression                 6                 0  
Withdrawal by Subject                 3                 1  
Adverse Event                 3                 0  
Death                 2                 4  
Alternative treatment                 3                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Arm A Patients receive low-dose melphalan 20 mg/m^2 IV over 15-30 minutes on day 1 or 0.12 mg/kg tablet orally once daily on days 1-7 and dexamethasone 40 mg orally on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses. (Study treatment beyond one year is not allowed.)
Arm B Patients receive filgrastim (G-CSF) 10 mg/kg/day on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan 140 mg/m^2 IV for low risk or 200 mg/m^2 IV for high risk patients over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.
Total Total of all reporting groups

Baseline Measures
    Arm A     Arm B     Total  
Number of Participants  
[units: participants]
  34     55     89  
Age  
[units: years]
Median (Full Range)
  62   (48 to 74)     57   (44 to 73)     59   (44 to 74)  
Gender  
[units: participants]
     
Female     17     16     33  
Male     17     39     56  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     0     1     1  
Native Hawaiian or Other Pacific Islander     0     1     1  
Black or African American     1     1     2  
White     32     51     83  
More than one race     0     0     0  
Unknown or Not Reported     1     1     2  
Region of Enrollment  
[units: participants]
     
United States     34     55     89  
ECOG Performance Score [1]
[units: participants]
     
0-1     25     50     75  
2     9     5     14  
Risk Group [2]
[units: participants]
     
Low     20     38     58  
High     14     17     31  
[1] Classifies patients according to their functional impairment. 0: Fully active, able to carry on all pre-disease performance without restriction; 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2: Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
[2]

Low Risk (requires all of the following): 1 or 2 organs involved, Cardiac EF >= 50%, Age <= 65 years, NYHA class 1 or 2, Alkaline phosphatase <= 4 x institutional ULN, cardiac involvement fully compensated or asymptomatic, serum creatinine <= 2.0 mg/dL

High Risk (any one of the following): >2 organs involved, Cardiac EF <50%, Age > 65 years, NYHA class 3, Alkaline phosphatase 4-6 x institutional ULN, symptomatic cardiac involvement, serum creatinine 2.1-3.0 mg/dL




  Outcome Measures
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1.  Primary:   Hematologic Response Rate   [ Time Frame: 10 years ]

2.  Secondary:   3 Year Overall Survival   [ Time Frame: 3 years ]

3.  Secondary:   Organ Response to Treatment   [ Time Frame: 10 years ]

4.  Post-Hoc:   3-Year Progression Free Survival   [ Time Frame: 3 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Dr. Morie Gertz
Organization: Mayo Clinic
e-mail: gertz.morie@mayo.edu


No publications provided


Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00477971     History of Changes
Other Study ID Numbers: CDR0000546745, P30CA015083, MC0482, 1691-05, NCI-2009-01329
Study First Received: May 23, 2007
Results First Received: June 23, 2015
Last Updated: June 23, 2015
Health Authority: United States: Federal Government