High-dose Cytarabine/Mitoxantrone Followed by Autotransplantation for t-MDS/t-AML

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT00774046
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arm: 1
• Duration (Months): 99
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effectiveness of a particular combination of drugs used to treat cancer.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome; Acute Myeloid Leukemia	Drug: Ara-C; Drug: Mitoxantrone; Drug: Etoposide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: High-dose Cytarabine/Mitoxantrone Followed by Autotransplantation for Therapy-Related Myelodysplastic Syndrome/Therapy -Related Acute Myeloid Leukemia
• Study Start Date: Dec 1, 2002
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Induction chemotherapy followed by stem cell transplant Ara-C Mitoxantrone Etoposide Stem cell mobilization Autologous transplant

Drug: Ara-C; Induction: 3000mg/m2 IV infusion for day 1 and day 5 Mobilization: within 2 weeks of end of induction therapy - 2000mg/m2 as 2 hour IV infusion once every 12 hours for 3 days (6 doses total); Other Names: Cytarabine HiDAC ; Drug: Mitoxantrone; Induction: 30mg/m2 after the end of HiDAC day 1 and day 5; Drug: Etoposide; Mobilization: 30mg/kg over 6 doses given once every 12 hours for 3 days; Other Names: VP-16

Outcome Measures

Primary Outcome Measures

1. Response to Induction Chemotherapy (CR or PR) [Day 28-40]

   Complete remission (CR): <5% bone marrow blasts with recovery of peripheral blood counts; complete cytogenetic remission, the disappearance of any pre-existing cytogenetic abnormality Partial remission (PR): >5% bone marrow blasts, but less than the pre-treatment blast percentage within the bone marrow Resistant disease (RD): no significant cytoreduction in bone marrow leukemic cells from pre-treatment levels Not evaluable (NE): patients who died during induction chemotherapy or who withdrew from follow-up before assessment could be made

2. Overall Survival [Up to 2000 days]

3. Relapse-free Survival [Up to 2000 days]

   Relapse is defined as bone marrow blasts >5% if the patient had achieved a complete remission, or the recurrence of any clonal cytogenetic abnormality.

Secondary Outcome Measures

1. Feasibility of Stem Cell Collection [1-5 days from initiation of stem cell collection]

   Feasibility is the ability to cryopreserve >=2.0 x 10^6 CD34+ cells/kg

2. Numbers of Stem Cells Collected [1-5 days from initiation of stem cell collection]

3. Overall Survival in Patients Undergoing Autologous Stem Cell Transplant [Up to 817 days]

4. Disease-free Survival in Patients Undergoing Autologous Stem Cell Transplant [Up to 883 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have received cytotoxic chemotherapy,radiation,or a drug known to affect the properties of DNA or cell growth for some condition other than acute myeloid leukemia prior to diagnosis.

• Patients must have t-MDS/t-AML

• To be eligible for allogeneic transplantation, patients must have a suitable donor who is HLA compatible.

• Patients must be over the age of 10.

• Patients must be reviewed and discussed at the Leukemia and Transplant Conferences of the Section of Hematology/Oncology.

Exclusion Criteria:

• Patients must not have any other serious medical condition(e.g.uncontrolled or severe cardiovascular disease, diabetes, pulmonary disease, or infection)

• Psychiatric condition which would prevent compliance or possibly be worsened by treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago

Investigators

• Principal Investigator: Lucy Godley, M.D., University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT00774046
• Other Study ID Numbers: 11884A
• First Posted: Oct 16, 2008
• Last Update Posted: Feb 11, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by University of Chicago: Therapy-related myelodysplastic syndrome/ Therapy -related Acute myeloid leukemia; Myelodysplastic syndrome; Acute myeloid leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Syndrome; Cytarabine; Etoposide; Mitoxantrone

Study Results

Participant Flow

Arm/Group Title	Induction Chemotherapy Followed by Stem Cell Transplant
Arm/Group Description	Ara-C Mitoxantrone Etoposide Stem cell mobilization Autologous transplant
Period Title: Screening
STARTED	116
COMPLETED	60
NOT COMPLETED	56
Period Title: Screening
STARTED	60
COMPLETED	32
NOT COMPLETED	28
Period Title: Screening
STARTED	32
COMPLETED	32
NOT COMPLETED	0
Period Title: Screening
STARTED	10
COMPLETED	7
NOT COMPLETED	3
Period Title: Screening
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Patients
Arm/Group Description	Ara-C Mitoxantrone Etoposide
Overall Participants	32
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56
Sex: Female, Male (Count of Participants)
Female	18 56.3%
Male	14 43.8%
Region of Enrollment (participants) [Number]
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	Response to Induction Chemotherapy (CR or PR)
Description	Complete remission (CR): <5% bone marrow blasts with recovery of peripheral blood counts; complete cytogenetic remission, the disappearance of any pre-existing cytogenetic abnormality Partial remission (PR): >5% bone marrow blasts, but less than the pre-treatment blast percentage within the bone marrow Resistant disease (RD): no significant cytoreduction in bone marrow leukemic cells from pre-treatment levels Not evaluable (NE): patients who died during induction chemotherapy or who withdrew from follow-up before assessment could be made
Time Frame	Day 28-40

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	Ara-C Mitoxantrone Etoposide
Measure Participants	32
Number (95% Confidence Interval) [percentage of participants]	81.2 253.8%

2. Primary Outcome

Title	Overall Survival
Time Frame	Up to 2000 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	Ara-C Mitoxantrone Etoposide
Measure Participants	32
Median (Inter-Quartile Range) [Days]	399

3. Primary Outcome

Title	Relapse-free Survival
Description	Relapse is defined as bone marrow blasts >5% if the patient had achieved a complete remission, or the recurrence of any clonal cytogenetic abnormality.
Time Frame	Up to 2000 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	Ara-C Mitoxantrone Etoposide
Measure Participants	32
Median (Inter-Quartile Range) [Days]	415

4. Secondary Outcome

Title	Feasibility of Stem Cell Collection
Description	Feasibility is the ability to cryopreserve >=2.0 x 10^6 CD34+ cells/kg
Time Frame	1-5 days from initiation of stem cell collection

Outcome Measure Data

Analysis Population Description

Subset of patients in CR who underwent mobilization and attempted stem cell collection.

Arm/Group Title	All Patients
Arm/Group Description	Ara-C Mitoxantrone Etoposide
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	70 218.8%

5. Secondary Outcome

Title	Numbers of Stem Cells Collected
Time Frame	1-5 days from initiation of stem cell collection

Outcome Measure Data

Analysis Population Description

Subset of patients in CR who underwent mobilization and attempted stem cell collection.

Arm/Group Title	All Patients
Arm/Group Description	Ara-C Mitoxantrone Etoposide
Measure Participants	10
Median (Full Range) [10^6 CD34+ cells/kg]	4.50

6. Secondary Outcome

Title	Overall Survival in Patients Undergoing Autologous Stem Cell Transplant
Time Frame	Up to 817 days

Outcome Measure Data

Analysis Population Description

Subset of patients undergoing autologous stem cell transplant

Arm/Group Title	All Patients
Arm/Group Description	Ara-C Mitoxantrone Etoposide
Measure Participants	4
Median (Full Range) [Days]	294

7. Secondary Outcome

Title	Disease-free Survival in Patients Undergoing Autologous Stem Cell Transplant
Time Frame	Up to 883 days

Outcome Measure Data

Analysis Population Description

Subset of patients undergoing autologous stem cell transplant

Arm/Group Title	All Patients
Arm/Group Description	Ara-C Mitoxantrone Etoposide
Measure Participants	4
Median (Full Range) [Days]	367

Adverse Events

Time Frame	2 months
Arm/Group Title	All Patients
Arm/Group Description	Ara-C Mitoxantrone Etoposide
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	7/32 (21.9%)
Gastrointestinal disorders
Hemorrhage	1/32 (3.1%)	1
General disorders
Hemorrhage	1/32 (3.1%)	1
Sudden death	1/32 (3.1%)	1
Infections and infestations
Neutropenic fever	1/32 (3.1%)	1
Infection with grade 4 neutrophils	3/32 (9.4%)	3
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	31/32 (96.9%)
Blood and lymphatic system disorders
Thrombocytopenia	8/32 (25%)
Cardiac disorders
Left ventrcular dysfunction	4/32 (12.5%)
Hypotension	4/32 (12.5%)
Tachycardia	2/32 (6.3%)
Atrial fibrillation	2/32 (6.3%)
Gastrointestinal disorders
Non-infectious diarrhea	8/32 (25%)
General disorders
Anemia	3/32 (9.4%)
Mental status changes	2/32 (6.3%)
Infections and infestations
Neutropenic fever	19/32 (59.4%)
Infection/sepsis	16/32 (50%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	3/32 (9.4%)
Respiratory failure	2/32 (6.3%)
Skin and subcutaneous tissue disorders
Rash	10/32 (31.3%)

Limitations/Caveats

[Not Specified]

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.