Trial record 12 of 288 for:    TRA

Phase I 5-Azacytidine Plus VPA Plus ATRA

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01575691
First received: April 9, 2012
Last updated: April 10, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndrome
Acute Myelogenous Leukemia
Drug: 5-Azacytidine (5-aza)
Drug: Valproic Acid
Drug: All-Trans Retinoic Acid (ATRA)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of the Combination of 5-azacytidine With Valproic Acid and All-trans Retinoic Acid in Patients With High Risk Myelodysplastic Syndrome and Acute Myelogenous Leukemia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximal tolerated dose (MTD) of valproic acid (VPA) in combination with 5-azacytidine (5-aza) and all-trans retinoic acid (ATRA) [ Time Frame: 28 day cycle ] [ Designated as safety issue: Yes ]
    MTD defined as the dose level below where either 0 dose limiting toxicities (DLTs) out of the first 3 participants, or 1 DLT in the first 3 participants, and 0 DLTs in following additional 3 participants of a cohort. The MTD designation will apply to cycle 1 (28 day cycle). Routine blood tests (about 1-2 teaspoons each time) 2-3 times a week.


Enrollment: 21
Study Start Date: July 2005
Study Completion Date: December 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VPA + 5-aza + ATRA
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)
Start at 75 mg/m^2 subcutaneously daily for 7 days.
Other Names:
  • Azacitidine
  • 5-azacytidine
  • 5-AZC
  • Vidaza
  • AZA-CR
  • Ladakamycin
  • NSC-102816
Drug: Valproic Acid
50 mg/kg daily by mouth for 7 days, same days as 5-aza.
Other Name: Depakene
Drug: All-Trans Retinoic Acid (ATRA)
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.
Other Names:
  • Tretinoin (oral)
  • Vesanoid

Detailed Description:

Participants receive 5-aza as an injection under the skin once a day for 7 days. This will be repeated every 3-8 weeks depending on blood counts and how well bone marrow is recovering. This is defined as 1 treatment cycle. Also during each cycle, participant will take VPA by mouth for 7 days and ATRA by mouth for 5 days. VPA will be given on the same days as 5-aza. ATRA will start on Day 3.

In the Phase I portion of the study, the dose of VPA will be increased in each new group of participants until the highest safe dose is found. A minimum of 3 participants and a maximum of 10 will be treated at each dose level.

  Eligibility

Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 * Upper Limits of Normal (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.

Exclusion Criteria:

  • 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.
  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: NCT01575691

Locations
United States, Texas
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Celgene Corporation
Investigators
Principal Investigator: Guillermo Garcia-Manero, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01575691     History of Changes
Other Study ID Numbers: 2004-0799 Phase I
Study First Received: April 9, 2012
Last Updated: April 10, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
All-trans retinoic acid
Tretinoin
Vesanoid
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
ATRA

Additional relevant MeSH terms:
Tretinoin
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Azacitidine
Valproic Acid
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Anticonvulsants
Central Nervous System Agents
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Keratolytic Agents

ClinicalTrials.gov processed this record on August 20, 2014