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)

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00569010
First received: December 5, 2007
Last updated: July 26, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Leukemia
Drug: Azacitidine
Drug: Ara-C
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase I/II Study of 5-Azacytidine in Combination With Cytosine Arabinoside in Patients With Relapsed/Refractory Acute Myelogenous Leukemia or High Risk Myelodysplastic Syndrome - "SPORE"

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Participants With Complete Remission [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (< 1% blasts in bone marrow with neutrophil recovery) according to International Working Group (IWG) criteria.


Enrollment: 36
Study Start Date: December 2005
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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

Drug: 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
Other Name: Vidaza
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)

Other Names:
  • Cytosar-U
  • cytarabine
  • cytosine Arabinoside
Experimental: 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

Drug: 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
Other Name: Vidaza
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)

Other Names:
  • Cytosar-U
  • cytarabine
  • cytosine Arabinoside
Experimental: 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
Drug: 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
Other Name: Vidaza
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)

Other Names:
  • Cytosar-U
  • cytarabine
  • cytosine Arabinoside
Experimental: 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

Drug: 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
Other Name: Vidaza
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)

Other Names:
  • Cytosar-U
  • cytarabine
  • cytosine Arabinoside

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00569010

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Celgene Corporation
Investigators
Principal Investigator: Jean-Pierre Issa, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00569010     History of Changes
Other Study ID Numbers: 2005-0291
Study First Received: December 5, 2007
Results First Received: January 21, 2011
Last Updated: July 26, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Acute Myelogenous Leukemia
AML
Myelodysplastic Syndrome
MDS
Leukemia

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid
Leukemia
Syndrome
Leukemia, Myeloid, Acute
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Neoplasms by Histologic Type
Disease
Pathologic Processes
Azacitidine
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2014