Decitabine, Cytarabine, GCSF for Refractory AML/MDS

• Sponsor: Brown University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00740181
• Collaborator: Memorial Hospital of Rhode Island (Other), Roger Williams Medical Center (Other)
• Enrollment: 9
• Location: 1
• Arm: 1
• Duration (Months): 20
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study will determine the activity of decitabine, low dose cytarabine (ARA-C) and G-CSF for patients with myelodysplasia and leukemia.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplasia; Leukemia	Drug: chemotherapy	Phase 2

Detailed Description

The primary objective of this study is to determine the feasibility and toxicity of decitabine, ARA-C and G-CSF for patients with myelodysplasia, refractory acute leukemia and poor performance status acute leukemia.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study With Decitabine, Low Dose Cytarabine and G-CSF in High-risk Myelodysplastic Syndromes, Refractory Acute Myeloid Leukemia or Acute Myeloid Leukemia in Patients With Significant Co-morbidities.
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy Decitabine 20 mg/m2 IV over 1 hr days 1-5 Cytarabine 20 mg/m2 subcut days 1-5 G-CSF 5mcg/kg subcut days 1-5	Drug: chemotherapy

Outcome Measures

Primary Outcome Measures

1. Response Rate [within 30 days of last treatment]

   Complete Response/Complete Remission: Complete remission (CR) is defined as the presence of all of the following: Peripheral blood - No leukemic blasts present. No extramedullary findings of leukemia or disappearance of such (i.e. CNS or soft tissue involvement) Bone marrow No Auer rods Less than 5% blast cells. CBC and bone marrow criteria must be met within one week of each other. Hemoglobin 9g/dl or greater Neutrophil count >1000 and platelet count >100,000. RBC Transfusion free for 2 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All patients must have histological confirmation of disease prior to enrollment on study.

• Patients with de novo AML who are not eligible for induction chemotherapy are eligible. Patients with refractory, relapsed AML are eligible.

• Patients with AML evolving from prior MDS or secondary to prior chemotherapy are eligible provided they are not eligible for standard induction chemotherapy.

• Patients with MDS and with blasts > 10% (RAEB-II) are eligible.

• Patients with extramedullary relapse only (i.e., leukemia cutis or other extramedullary site) are eligible as long as disease can be monitored.

• Patients who have relapsed after standard autologous and/or allogeneic bone marrow transplant are eligible as long as they meet all other eligibility criteria.

• Patients must not have had any chemotherapy, except hydrea, or radiation for at least 4 weeks prior.

• Patients must be > 18 years of age.

• Patients with an active second malignancy other than non-melanoma skin cancers are not eligible.

• Patients must have an expected life expectancy of > 12 weeks at the time of enrollment.

• Patients with visceral, blood stream or nervous system opportunistic infection are eligible if the infection has been appropriately treated and controlled. Patients with fungal lung infections must have had treatment for at least one month and have proof of regression prior to enrollment. Patients may be on antimicrobials at the time of therapy.

• Initial required laboratory values:

• Total Bilirubin < 2 X upper limit of normal.

• AST & ALT < 3 X upper limit of normal (if elevated liver enzymes thought likely due to Leukemic infiltrate discuss with the Principal Investigator and the BrUOG Central Office).

• Creatinine < 2 mg/dl.

• < 15,000 K/uI blast count-Hydroxyurea can be used to decrease count if more than 15,000 K/ul.

• Patients must have an ECOG performance status of 0-2.

• Patients must receive and sign a full informed consent.

• Patients should not have co-existing medical illnesses which would limit survival < 12 weeks.

• No known history of HIV.

• The safety of decitabine in human pregnancy is unknown. Based on animal studies, decitabine may cause fetal harm when administered to a pregnant woman. Therefore, it is important that you do not become pregnant or father a child while receiving study medication and for 2 months afterwards because the drugs in this study may affect an unborn baby.

• If you are a woman capable of becoming pregnant (not surgically sterile or post-menopausal), you must have a negative pregnancy test before beginning treatment.

If you do become pregnant, suspect you are pregnant, or if your partner becomes pregnant while you are on this study, you must notify your study doctor immediately. If you become pregnant, you will be taken off this study.

In addition, you must not breast feed at any time you are on this study since any drugs you are taking may also affect the child.

If you are capable of giving birth to or fathering a child, you must agree to use a form of birth control (examples of effective birth control are: a condom or a diaphragm with spermicidal jelly; oral, injectable, or implanted birth control; or abstinence) that is medically acceptable to your study doctor while taking part in this research study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lifespan Hospitals	Providence	Rhode Island	United States	02903

Sponsors and Collaborators

• Brown University
• Memorial Hospital of Rhode Island
• Roger Williams Medical Center

Investigators

• Principal Investigator: James Butera, Brown University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Brown University
• ClinicalTrials.gov Identifier: NCT00740181
• Other Study ID Numbers: BrUOG-AML-217; MGI Pharma#DAC 022/2007
• First Posted: Aug 22, 2008
• Last Update Posted: Jan 14, 2022
• Last Verified: Jan 1, 2022

• Keywords provided by Brown University: myelodysplasia; refractory leukemia; acute leukemia
• Additional relevant MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes

Study Results

Participant Flow

Recruitment Details	9 patients were enrolled beginning April 2009 to February 2010

Arm/Group Title	Chemotherapy
Arm/Group Description	Decitabine 20 mg/m2 IV over 1 hr days 1-5 Cytarabine 20 mg/m2 subcut days 1-5 G-CSF 5mcg/kg subcut days 1-5
Period Title: Overall Study
STARTED	9
COMPLETED	9
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Chemotherapy
Arm/Group Description	Decitabine 20 mg/m2 IV over 1 hr days 1-5 Cytarabine 20 mg/m2 subcut days 1-5 G-CSF 5mcg/kg subcut days 1-5
Overall Participants	9
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 11.1%
>=65 years	8 88.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73 (5)
Sex: Female, Male (Count of Participants)
Female	4 44.4%
Male	5 55.6%
Region of Enrollment (participants) [Number]
United States	9 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Complete Response/Complete Remission: Complete remission (CR) is defined as the presence of all of the following: Peripheral blood - No leukemic blasts present. No extramedullary findings of leukemia or disappearance of such (i.e. CNS or soft tissue involvement) Bone marrow No Auer rods Less than 5% blast cells. CBC and bone marrow criteria must be met within one week of each other. Hemoglobin 9g/dl or greater Neutrophil count >1000 and platelet count >100,000. RBC Transfusion free for 2 weeks.
Time Frame	within 30 days of last treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy
Arm/Group Description	Decitabine 20 mg/m2 IV over 1 hr days 1-5 Cytarabine 20 mg/m2 subcut days 1-5 G-CSF 5mcg/kg subcut days 1-5
Measure Participants	9
Number [participants]	1 11.1%

Adverse Events

Time Frame	Pre-study and prior to each cycle of treatment (on average for 2 cycles, approximately 8-10 weeks)
Arm/Group Title	Chemotherapy
Arm/Group Description	Decitabine 20 mg/m2 IV over 1 hr days 1-5 Cytarabine 20 mg/m2 subcut days 1-5 G-CSF 5mcg/kg subcut days 1-5
All Cause Mortality
	Chemotherapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Chemotherapy
	Affected / at Risk (%)	# Events
Total	8/9 (88.9%)
Investigations
fever	2/9 (22.2%)	2
death within 30 days treatment- disease related	3/9 (33.3%)	3
dyspnea/penumonitis and bilateral infiltrates , death within 30 days of treatment	1/9 (11.1%)	1
hemmorrhage-brain, pain-neuro(H/A), weakness	1/9 (11.1%)	1
infection	1/9 (11.1%)	1
acute respiratory failure- death not related, neutropenic fever - not related	1/9 (11.1%)	1
infection, neutropenia	1/9 (11.1%)	1
fever, infection/pulmonary/upper respiratory (pneumonia)	1/9 (11.1%)	1
PLT, hemorrhage bladder & CHF/L ventricular systolic dysfunction, infection-pulmonary	1/9 (11.1%)	1
thrombocytopenia, mucositis, dehydration, dysphagia, syncope, anemia	1/9 (11.1%)	1
hypoxic respiratory failure and septic shock- possibly related	1/9 (11.1%)	1
thrombocytopenia, hypoxia, pleural effusion	1/9 (11.1%)	1
syncopal episodes and anemia	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Chemotherapy
	Affected / at Risk (%)	# Events
Total	0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

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.