Phase I/II Study of 5-Azacytidine With Ara-C in Patients With Relapsed/Refractory Acute Myelogenous Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)

NCT ID: NCT00569010

Last Updated: 2012-08-01

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-12-31

Study Completion Date

2009-10-31

Brief Summary

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The goal of this clinical research study is to find the highest tolerable dose of Azacytidine (5-azacytidine) combined with cytosine arabinoside (ara-C) for the treatment of patients with relapsed and/or refractory Acute Myeloid Leukemia (AML) or high-risk Myelodysplastic Syndrome (MDS). The safety and effectiveness of this treatment combination will also be studied.

Detailed Description

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5-azacytidine is designed to "turn off" the growth of cancer cells. This may be increased by ara-C, which is designed to kills leukemia cells by helping to stop the cells from dividing.

If you are found to be eligible to take part in this study, you will be assigned to a treatment group. You will be randomly assigned (as in the toss of a coin) to one of the 4 treatment groups. The first 3 to 6 patients will be assigned to Group 1. If no serious side effects are experienced, the next 3 to 6 patients will be assigned to Group 2. If no serious side effects are experienced, the next 3 to 6 patients will be assigned to Group 3. If no serious side effects are experienced, the next 3 to 6 patients will be assigned to Group 4.

If you are in Group 1, you will receive low-dose 5-azacytidine as an infusion by vein over 20 to 30 minutes every day for 7 days. You will also receive low-dose ara-C as a continuous infusion by vein for 7 days.

If you are in Group 2, you will receive high-dose 5-azacytidine as an infusion by vein over 20 to 30 minutes every day for 7 days. You will also receive low-dose ara-C as a continuous infusion by vein for 7 days.

If you are in Group 3, you will receive low-dose 5-azacytidine as an infusion by vein over 20 to 30 minutes every day for 7 days. You will also receive high-dose ara-C as a continuous infusion by vein for 3 days (if you are 65 years of age or older) or for 4 days (if you are younger than 65 years of age).

If you are in Group 4, you will receive high-dose 5-azacytidine as an infusion by vein over 20 to 30 minutes every day for 7 days. You will also receive high-dose ara-C as a continuous infusion by vein for 3 days (if you are 65 years of age or older) or for 4 days (if you are younger than 65 years of age).

Each group's treatment will be repeated every 4 to 8 weeks (this is considered 1 cycle of treatment), depending on your blood counts and how well your bone marrow is recovering. You will receive at least 2 cycles of treatment. You will continue to receive treatment, unless your disease gets worse or if you experience intolerable side effects. If your disease gets worse or you experience intolerable side effects, you may be taken off this study.

This is an investigational study. 5-azacytidine has been approved by the FDA for the treatment of MDS. Ara-C has been approved by the FDA for the treatment of AML. Up to 80 patients will take part in this study. All will be enrolled at M. D. Anderson.

Conditions

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Acute Myelogenous Leukemia Myelodysplastic Syndrome Leukemia

Keywords

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Acute Myelogenous Leukemia AML Myelodysplastic Syndrome MDS Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Low-Dose Ara-C + AZA-Level 0

Group 1 = Low-Dose Ara-C + Azacitidine-Level 0

Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days Azacitidine (AZA): 37.5 mg/m\^2 intravenous (IV) Over 20-30 minutes Daily for 7 Days

Group Type EXPERIMENTAL

Azacitidine

Intervention Type DRUG

Group 1 and 3 at Level 0 = 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days Group 2 and 4 at Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days

Ara-C

Intervention Type DRUG

Group 1 and 2 at Low-Dose = 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days

Arms 3 and 4 at High-dose = 1 g/m\^2 Daily CIV for 4 days (age\<65 years) or 3 days (age\>=65 years)

Low-Dose Ara-C + AZA-Level 1

Group 2 = Low-Dose Ara-C + Azacitidine-Level 1

Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days

Group Type EXPERIMENTAL

Azacitidine

Intervention Type DRUG

Group 1 and 3 at Level 0 = 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days Group 2 and 4 at Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days

Ara-C

Intervention Type DRUG

Group 1 and 2 at Low-Dose = 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days

Arms 3 and 4 at High-dose = 1 g/m\^2 Daily CIV for 4 days (age\<65 years) or 3 days (age\>=65 years)

High-Dose Ara-C + AZA-Level 0

Group 3 = High-Dose Ara-C + Azacitidine-Level 0 High-dose Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65years) AZA: 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days

Group Type EXPERIMENTAL

Azacitidine

Intervention Type DRUG

Group 1 and 3 at Level 0 = 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days Group 2 and 4 at Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days

Ara-C

Intervention Type DRUG

Group 1 and 2 at Low-Dose = 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days

Arms 3 and 4 at High-dose = 1 g/m\^2 Daily CIV for 4 days (age\<65 years) or 3 days (age\>=65 years)

High-Dose Ara-C + AZA-Level 1

Group 4 = High-Dose Ara-C + Azacitidine-Level 1

High-dose Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65 years) AZA:Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days

Group Type EXPERIMENTAL

Azacitidine

Intervention Type DRUG

Group 1 and 3 at Level 0 = 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days Group 2 and 4 at Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days

Ara-C

Intervention Type DRUG

Group 1 and 2 at Low-Dose = 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days

Arms 3 and 4 at High-dose = 1 g/m\^2 Daily CIV for 4 days (age\<65 years) or 3 days (age\>=65 years)

Interventions

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Azacitidine

Group 1 and 3 at Level 0 = 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days Group 2 and 4 at Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days

Intervention Type DRUG

Ara-C

Group 1 and 2 at Low-Dose = 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days

Arms 3 and 4 at High-dose = 1 g/m\^2 Daily CIV for 4 days (age\<65 years) or 3 days (age\>=65 years)

Intervention Type DRUG

Other Intervention Names

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Vidaza Cytosar-U cytarabine cytosine Arabinoside

Eligibility Criteria

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Inclusion Criteria

1. Patients must have histologically confirmed Acute Myeloid Leukemia (AML) or high risk and previously treated Myelodysplastic Syndrome (MDS).
2. Patients with (1) refractory disease or (2) first relapse within 6 months of therapy or (3) 2nd or more of relapse of Acute Myelogenous Leukemia (AML) or high risk Myelodysplastic Syndrome MDS will be considered for the study.
3. Patients must have been off chemotherapy for 4 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease.
4. Age \>=18 years. Deoxyribonucleic acid (DNA) methylation plays a significant role in development, and the effects of azacitidine in children are not well described.
5. Patients must have normal organ as defined: Total bilirubin \<2 mg, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \<2.5 x institutional upper limit of normal, Creatinine \<2 mg
6. Ability to understand and the willingness to sign a written informed consent document.
7. Women of child bearing potential must have a negative serum pregnancy test prior to azacitidine treatment.
8. Women of child bearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacytidine.
9. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion Criteria

1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier, unless there is evidence of rapidly progressive disease. Patients may have received hydroxyurea prior to entering the study.
2. Patients may not be receiving any other investigational agents for their leukemias.
3. Patients with active brain or meningeal disease should be excluded.
4. Known or suspected hypersensitivity to azacitidine or mannitol
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
6. Pregnant women are excluded from this study because azacitidine is a Deoxyribonucleic acid (DNA) methyltransferase inhibitor which has teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azacitidine, breastfeeding should be discontinued if the mother is treated with azacitidine.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene Corporation

INDUSTRY

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Pierre Issa, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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U.T.M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://mdanderson.org

M.D. Anderson's Website

Other Identifiers

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2005-0291

Identifier Type: -

Identifier Source: org_study_id