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Gemcitabine and Mitoxantrone in Treating Patients With Relapsed Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT00268242
Recruitment Status : Terminated (If </= 5 of the initial 18 patients had a CR, the study would be stopped. Only 5 patients (21%) of 24 enrolled patients had a CR so the study was terminated.)
First Posted : December 22, 2005
Results First Posted : October 5, 2015
Last Update Posted : February 22, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Duke University
Information provided by (Responsible Party):
The Cleveland Clinic

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia
Interventions Drug: Gemcitabine Hydrochloride
Drug: Mitoxantrone Hydrochloride
Enrollment 24
Recruitment Details Patients were treated at the Cleveland Clinic or Duke University Medical Center during the years 2005-2008.
Pre-assignment Details If </= 5 of the initial 18 patients enrolled achieved a CR, the study would be stopped. Accrual was not halted while follow-up of the first 18 evaluable patients was under way. Therefore, 24 patients were enrolled. Only 5 patients (21%) achieved a CR and therefore, the study was terminated.
Arm/Group Title Gemcitabine + Mitoxantrone
Hide Arm/Group Description

Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3.

Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours

Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3

Period Title: Overall Study
Started 24
Completed 23
Not Completed 1
Reason Not Completed
Death             1
Arm/Group Title Gemcitabine + Mitoxantrone
Hide Arm/Group Description

Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3.

Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours

Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3

Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 24 participants
51
(28 to 74)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
10
  41.7%
Male
14
  58.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 24 participants
24
1.Primary Outcome
Title Complete Response Rate
Hide Description Assumptions/ hypothesis: A Complete Response (CR) rate of 30% or less is unacceptable, and 50% or more is promising. A two-stage design will be used. Initially, 18 patients will be enrolled. If 5 or fewer achieve CR, the study will be stopped. Otherwise, an additional 22 patients will be accrued. Accrual was not halted while follow-up of the first 18 evaluable patients was under way. Therefore, 24 patients were enrolled. Four weeks is anticipated for observation for response. Only 5 patients (21%) achieved a CR and therefore, the study was terminated. Since response was assessed using the International Working Group criteria, a complete response was determined by Morphologic complete remission: A CR designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of ≥ 100,000/μL, a cytogenic CR and a morphologic CR with incomplete blood count recovery (CRi).
Time Frame 4 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
A total of 5 patients (21%) achieved a complete response.
Arm/Group Title Gemcitabine + Mitoxantrone
Hide Arm/Group Description:

Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3.

Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours

Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
5
2.Primary Outcome
Title Duration of the First Complete Response
Hide Description [Not Specified]
Time Frame After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Only 5 patients had a complete response, therefore on 5 patients were analyzed for this measure.
Arm/Group Title Gemcitabine + Mitoxantrone
Hide Arm/Group Description:

Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3.

Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours

Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3

Overall Number of Participants Analyzed 5
Median (Full Range)
Unit of Measure: months
7.3
(2.9 to 30.3)
3.Secondary Outcome
Title Disease-free and Overall Survival
Hide Description [Not Specified]
Time Frame After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years.
Hide Outcome Measure Data
Hide Analysis Population Description
1 patient died on day 1 of protocol therapy (secondary to complications from AML).
Arm/Group Title Gemcitabine + Mitoxantrone
Hide Arm/Group Description:

Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3.

Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours

Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
Patients dead >30 days post-tx, no relapse 1
Patients alive with no evidence of disease relapse 4
Patient death on Day 1 of Protocol Therapy 1
Patients dead >30 days post-tx, after relapse 18
4.Secondary Outcome
Title Laboratory Correlates: Immunohistochemistry
Hide Description

Percentage of patients who had a moderate-strong (2-3+) expression of multidrug resistance (MDR) genes by immunohistochemistry.

  • Multidrug resistance gene 1 (MDR1)
  • Equilibrative nucleoside transporter 2(SLC29A2)
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
23 of 24 patients had available blocks for Immunohistochemical (IHC) analysis; Participants with the SLC29A2 Gene Expression (n=22)
Arm/Group Title Gemcitabine + Mitoxantrone
Hide Arm/Group Description:

Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3.

Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours

Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3

Overall Number of Participants Analyzed 23
Measure Type: Number
Unit of Measure: percentage of participants
Participants with GSTP1 Gene Expression 70
Participants with SLC29A2 Gene Expression 55
Participants with MRP1 Gene Expression 43
Participants with LRP1 Gene Expression 35
Participants with MDR1 Gene Expression 22
5.Secondary Outcome
Title White Blood Cell Count at Time of Relapse
Hide Description [Not Specified]
Time Frame After a CR is achieved, patient will be followed at 3 month intervals for disease progression, typically for up to 5 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Gemcitabine + Mitoxantrone
Hide Arm/Group Description:

Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3.

Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours

Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3

Overall Number of Participants Analyzed 24
Median (Full Range)
Unit of Measure: cells per microliter
3450
(800 to 233,500)
6.Secondary Outcome
Title Percentage of Patients Making it to Bone Marrow Transplant.
Hide Description Assessing the number of patients who were able to have protocol treatment and have a bone marrow transplant after treatment.
Time Frame After completion of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Gemcitabine + Mitoxantrone
Hide Arm/Group Description:

Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3.

Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours

Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage of Patients completed a BMT
8
Time Frame [Not Specified]
Adverse Event Reporting Description All Adverse Event (AE) / Serious Adverse Event (SAE) data grades were included together in data reporting; there was no differentiation between AEs and SAEs and no unexpected toxicities were seen. Since all grades were reported together, they are being listed as Serious for that reason.
 
Arm/Group Title Gemcitabine + Mitoxantrone
Hide Arm/Group Description

Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3.

Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours

Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3

All-Cause Mortality
Gemcitabine + Mitoxantrone
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Gemcitabine + Mitoxantrone
Affected / at Risk (%)
Total   24/24 (100.00%) 
Gastrointestinal disorders   
Nausea   16/24 (66.67%) 
Mucositis   14/24 (58.33%) 
Diarrhea   14/24 (58.33%) 
Abdominal Pain   9/24 (37.50%) 
General disorders   
Pain   16/24 (66.67%) 
Infections and infestations   
Fever or Infection   20/24 (83.33%) 
Musculoskeletal and connective tissue disorders   
Fatigue   12/24 (50.00%) 
Skin and subcutaneous tissue disorders   
Rash   19/24 (79.17%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Gemcitabine + Mitoxantrone
Affected / at Risk (%)
Total   0/24 (0.00%) 
If </= 5 of 1st 18 pts had a CR, study would stop (otherwise, another 22 pts would be accrued). Study would stop if >4 of 1st 10 or 10 of 1st 25 pts had unacceptable toxicity per protocol & Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
Name/Title: Anjali S. Advani, MD
Organization: The Cleveland Clinic
Phone: 216-445-5330
Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT00268242     History of Changes
Other Study ID Numbers: CASE-CCF-7725
P30CA043703 ( U.S. NIH Grant/Contract )
CASE-CCF-7725 ( Other Identifier: Cleveland Clinic )
First Submitted: December 20, 2005
First Posted: December 22, 2005
Results First Submitted: June 3, 2015
Results First Posted: October 5, 2015
Last Update Posted: February 22, 2018