Phase II 5-Azacytidine Plus VPA Plus ATRA

NCT00326170 | Completed Phase 2 Results

• 1 other identifier: 2004-0799
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

5-aza is a chemotherapy drug with activity in leukemia and myelodysplastic syndromes (MDS). Researchers hope that valproic acid (VPA) and all-trans retinoic acid (ATRA)will increase the effects of 5-aza. The goal of this clinical research study is to find the highest safe dose of valproic acid (VPA) that can be given in combination with 5-azacytidine (5-aza) and all-trans retinoic acid (ATRA) in the treatment of AML and MDS. The safety and effectiveness of this combination therapy will also be studied. Additional blood and bone marrow samples will be requested. These samples will be used to evaluate the effect of the treatment on leukemic cells. In addition, any leftover blood and bone marrow samples that are collected at the start of the study and during the regularly scheduled evaluations to be sent for research studies. The research studies will examine changes in the blood and bone marrow cells that might help explain the causes of leukemia and MDS and how the combination of 5-aza, VPA, and ATRA works.

Conditions

Myelodysplastic Syndrome; Acute Myelogenous Leukemia

Keywords

Combination Chemotherapy; MDS; High-Risk Myelodysplastic Syndrome; AML; Acute myelogenous leukemia; valproic acid; VPA; Depakene; 5-azacytidine; 5-aza; Azacitidine; 5-AZC; Vidaza; AZA-CR; Ladakamycin; NSC-102816; All-trans retinoic acid; ATRA; Tretinoin; Vesanoid

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Response

  Clinical activity of combination defined as: Complete Response (CR), bone marrow with 5% or fewer blasts and peripheral blood count with an absolute neutrophil count of 10\^9/L or more and platelet count of 100x10\^9 or more; Complete response without platelets (CRp), a complete response except for a platelet count less than 100x10\^9 and transfusion independent; and Bone Marrow (BM) Response, bone marrow blast of 5% or less but without meeting the peripheral blood count criteria for (CR) or (CRp).

  Up to 12 cycles of treatment (28 day cycles)

Study Arms (1)

VPA + 5-aza + ATRA

EXPERIMENTAL

Daily for 7 days, Valproic acid (VPA) starting dose 75 mg/m\^2 subcutaneously in combination with 5-azacytidine (5-aza) 50 mg/kg orally; and all-trans retinoic acid (ATRA) 45 mg/m\^2 orally daily (in two divided doses) for 5 days starting on day 3.

Drug: 5-Azacytidine (5-aza); Drug: Valproic Acid; Drug: All-Trans Retinoic Acid (ATRA)

Interventions

5-Azacytidine (5-aza) DRUG

Start at 75 mg/m\^2 subcutaneously daily for 7 days.

Also known as: Azacitidine, 5-azacytidine, 5-AZC, Vidaza, AZA-CR, Ladakamycin, NSC-102816

VPA + 5-aza + ATRA

Valproic Acid DRUG

50 mg/kg daily by mouth for 7 days, same days as 5-aza.

Also known as: Depakene

VPA + 5-aza + ATRA

All-Trans Retinoic Acid (ATRA) DRUG

45 mg/m\^2 orally daily (in two divided doses) for 5 days starting on day 3 of the administration of 5-aza and VPA.

Also known as: Tretinoin (oral), Vesanoid

VPA + 5-aza + ATRA

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with refractory or relapsed: acute myelogenous leukemia (AML), and myelodysplastic syndrome (MDS) (bone marrow blasts \> or = 10%) are eligible.
• Untreated patients older than 60 years of age with AML or MDS (bone marrow blasts \> or = 10%) who refuse or are not eligible for front-line chemotherapy, are eligible.
• Performance status of \< or = 2 by the Eastern Cooperative Oncology Group (ECOG) scale.
• Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of University of Texas M D Anderson Cancer Center (UTMDACC).
• Age \> 2 years. Valproic acid has been associated with a higher rate of severe liver toxicity in children younger than 2 years.
• Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Use of hydroxyurea for patients with rapidly proliferative disease is allowed for the first two weeks on therapy.
• Adequate liver function (bilirubin of \< 2mg/dL, SGPT \< 3 \* ULN) and renal function (creatinine \< 2mg/dL).
• Women of childbearing potential must practice contraception. Men and women must continue birth control for the duration of the trial.
• Patients with relapsed /refractory disease with inv16, t(8;21) or t(15;17) are eligible.

You may not qualify if:

• Nursing and pregnant females are excluded.
• Patients with active and uncontrolled infections are excluded.
• Patients already receiving valproic acid or receiving other anticonvulsants will be excluded.
• Untreated patients younger than 60 years will not be candidates for this study.
• Patients with untreated disease inv16, t(8;21) or t(15;17) will be excluded.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Celgene Corporation: collaborator

Study Sites (1)

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Soriano AO, Yang H, Faderl S, Estrov Z, Giles F, Ravandi F, Cortes J, Wierda WG, Ouzounian S, Quezada A, Pierce S, Estey EH, Issa JP, Kantarjian HM, Garcia-Manero G. Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood. 2007 Oct 1;110(7):2302-8. doi: 10.1182/blood-2007-03-078576. Epub 2007 Jun 27.

  PMID: 17596541 DERIVED

Related Links

• M.D. Anderson's internet website

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Azacitidine; Valproic Acid; Tretinoin

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Fatty Acids; Lipids; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Results Point of Contact

• Title: Guillermo Garcia-Manero, MD / Associate Professor
• Organization: UT MD Anderson Cancer Center

eharriso@mdanderson.org

713-792-7305

Study Officials

• Guillermo Garcia-Manero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2006
• First Posted: May 16, 2006
• Study Start: July 1, 2005
• Primary Completion: July 1, 2007
• Study Completion: December 1, 2007
• Last Updated: June 15, 2012
• Results First Posted: July 11, 2011

Record last verified: 2012-06

Locations

US (1)