AMD3100 Plus Mitoxantrone, Etoposide and Cytarabine in Acute Myeloid Leukemia (AMD3100+MEC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00512252
First received: August 6, 2007
Last updated: September 12, 2014
Last verified: September 2014
Results First Received: July 28, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Leukemia, Myeloid, Acute
Interventions: Drug: AMD3100
Drug: Mitoxantrone
Drug: Etoposide
Drug: Cytarabine

  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
Recruitment occurred from 07/12/2007 until 01/14/2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Phase I Dose Escalation (Dose Level 1)
  • AMD3100 SQ on days 0-5
  • Mitoxantrone on days 1-5
  • Etoposide on days 1-5
  • Cytarabine on days 1-5

Dose Level 1 AMD3100 dose = 80 mcg/kg/d

Phase I Dose Escalation (Dose Level 2)
  • AMD3100 SQ on days 0-5
  • Mitoxantrone on days 1-5
  • Etoposide on days 1-5
  • Cytarabine on days 1-5

Dose Level 2 AMD3100 dose = 160 mcg/kg/d

Phase II Dose Treatment (Dose Level 3)
  • AMD 3100 SQ on days 0-5
  • Mitoxantrone on days 1-5
  • Etoposide on days 1-5
  • Cytarabine on days 1-5

Dose Level 3 AMD3100 dose=240 mcg/kg/d (this was the Phase II dose).

The 6 participants that were enrolled in Dose Level 3 in the Phase I portion of the study were carried over to the Phase II analysis. 40 additional patients were enrolled in the Phase II portion of the study using the Dose Level 3 dose.


Participant Flow:   Overall Study
    Phase I Dose Escalation (Dose Level 1)     Phase I Dose Escalation (Dose Level 2)     Phase II Dose Treatment (Dose Level 3)  
STARTED     3     3     46  
COMPLETED     3     3     43  
NOT COMPLETED     0     0     3  
Lost to Follow-up                 0                 0                 1  
Protocol Violation                 0                 0                 1  
Death                 0                 0                 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.
The 6 participants that were enrolled in Dose Level 3 in the Phase I portion of the study were carried over to the Phase II analysis. 40 additional patients were enrolled in the Phase II portion of the study using the Dose Level 3 dose.

Reporting Groups
  Description
Phase I Dose Escalation (Dose Level 1)
  • AMD3100 SQ on days 0-5
  • Mitoxantrone on days 1-5
  • Etoposide on days 1-5
  • Cytarabine on days 1-5

Dose Level 1 AMD3100 dose = 80 mcg/kg/d

Phase I Dose Escalation (Dose Level 2)
  • AMD3100 SQ on days 0-5
  • Mitoxantrone on days 1-5
  • Etoposide on days 1-5
  • Cytarabine on days 1-5

Dose Level 2 AMD3100 dose = 160 mcg/kg/d

Phase II Dose Treatment (Dose Level 3)
  • AMD 3100 SQ on days 0-5
  • Mitoxantrone on days 1-5
  • Etoposide on days 1-5
  • Cytarabine on days 1-5

Dose Level 3 AMD3100 dose=240 mcg/kg/d (this was the Phase II dose).

The 6 participants that were enrolled in Dose Level 3 in the Phase I portion of the study were carried over to the Phase II analysis. 40 additional patients were enrolled in the Phase II portion of the study using the Dose Level 3 dose.

Total Total of all reporting groups

Baseline Measures
    Phase I Dose Escalation (Dose Level 1)     Phase I Dose Escalation (Dose Level 2)     Phase II Dose Treatment (Dose Level 3)     Total  
Number of Participants  
[units: participants]
  3     3     46     52  
Age  
[units: participants]
       
<=18 years     0     0     1     1  
Between 18 and 65 years     3     3     40     46  
>=65 years     0     0     5     5  
Age  
[units: years]
Median ( Full Range )
  58  
  ( 44 to 62 )  
  24  
  ( 22 to 39 )  
  51  
  ( 18 to 71 )  
  51  
  ( 18 to 71 )  
Gender  
[units: participants]
       
Female     2     2     26     30  
Male     1     1     20     22  
Region of Enrollment  
[units: participants]
       
United States     3     3     46     52  
Acute myeloid leukemia (AML) source [1]
[units: participants]
       
De novo AML     3     2     36     41  
Therapy related     0     1     4     5  
Prior MDS/MPD     0     0     6     6  
Prior transplantation  
[units: participants]
       
Autologous     0     0     3     3  
Allogeneic     0     0     6     6  
No prior transplant     3     3     37     43  
Eastern Cooperative Oncology Group (ECOG) Performance Status [2]
[units: participants]
       
0     2     2     25     29  
1     1     1     10     12  
2     0     0     3     3  
Unknown     0     0     8     8  
Treatment Indication  
[units: participants]
       
First relapse, first salvage     3     2     32     37  
Primary refractory     0     1     10     11  
>=Second relapse/salvage     0     0     4     4  
[1] MDS = myelodysplastic syndrome MPD = myeloproliferative disease
[2]

Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 Fully active able to carry on all predisease performance without restriction

  1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (light house work/office work)
  2. Ambulatory, capable of all selfcare but unable to carry out any work activities. Up & about more than 50% of waking hours
  3. Capable of limited selfcare, confined to bed/chair more than 50% of waking hours
  4. Completely disabled. Cannot carry on selfcare. Totally confined to bed/chair
  5. Dead



  Outcome Measures
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1.  Primary:   Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML   [ Time Frame: Completion of all patients in Phase I portion (232 days) ]

2.  Primary:   Phase II Only: Complete Response Rate of AMD3100 + MEC   [ Time Frame: 42 days ]

3.  Primary:   Ability of AMD3100 + MEC to Induce dsDNA Damage and Apoptosis in Leukemic Blasts From Bone Marrow or Peripheral Blood Fractions   [ Time Frame: 42 days ]

4.  Secondary:   Safety and Tolerability of AMD3100 + MEC.   [ Time Frame: 42 days ]

5.  Secondary:   Time to Neutrophil Recovery   [ Time Frame: 42 days ]

6.  Secondary:   Time to Platelet Recovery   [ Time Frame: 42 days ]

7.  Secondary:   Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I)   [ Time Frame: Day 0 ]

8.  Secondary:   Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I)   [ Time Frame: Day 0 ]

9.  Secondary:   Pharmacokinetics of AMD3100 on MEC   [ Time Frame: Day 1 - Phase 2 only ]

10.  Secondary:   Time to Progression   [ Time Frame: Every 6 months ]

11.  Secondary:   Treatment Failure   [ Time Frame: 42 days ]

12.  Secondary:   Overall Survival   [ Time Frame: 1 year ]

13.  Secondary:   Relapse-free Survival   [ Time Frame: 1 year ]


  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: Geoffrey L. Uy, M.D.
Organization: Washington University School of Medicine
phone: 314-454-8304
e-mail: guy@dom.wustl.edu


No publications provided by Washington University School of Medicine

Publications automatically indexed to this study:

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00512252     History of Changes
Other Study ID Numbers: 07-0227 / 201011796
Study First Received: August 6, 2007
Results First Received: July 28, 2014
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration