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Study of Decitabine Alone or in Combination With Valproic Acid and All-trans Retinoic Acid in Acute Myeloid Leukemia (DECIDER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00867672
Recruitment Status : Completed
First Posted : March 24, 2009
Last Update Posted : August 31, 2016
Sponsor:
Information provided by (Responsible Party):
Michael Luebbert, University Hospital Freiburg

Brief Summary:
AML of the older patient constitutes a major unmet clinical need since the large majority will not be found eligible for induction chemotherapy. Reasons for this decision include host factors (comorbidities, reduced performance status, functional limitations due to age), leading to often poor tolerance of repeated chemotherapy courses and the unfavorable biology underlying this disease in older patients. Low dose Decitabine has shown very promising efficacy in high-risk MDS and is therefore a very promising approach also in older AML patients. Preliminary results from several centres have demonstrated excellent feasibility and good efficacy of this treatment. Therefore the investigators intend to investigate the effects of two drugs added onto low-dose Decitabine which have shown very promising synergistic effects in vitro and for which preliminary results indicate that the combination with low-dose Decitabine is very feasible.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Decitabine Drug: VPA Drug: ATRA Phase 2

Detailed Description:
By employing a 2x2 factorial design, this phase II study will address the possible added efficacy of addition of one or even both of these agents to low-dose Decitabine. The primary endpoint of this study will be objective response rate (complete and partial remissions).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 204 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Randomized Multicenter Phase II Trial of Low-dose Decitabine (DAC) Administered Alone or in Combination With the Histone Deacetylase Inhibitor Valproic Acid (VPA) and All-trans Retinoic Acid (ATRA) in Patients > 60 Years With Acute Myeloid Leukemia Who Are Ineligible for Induction Chemotherapy
Study Start Date : August 2011
Actual Primary Completion Date : February 2015
Actual Study Completion Date : February 2016


Arm Intervention/treatment
Experimental: Decitabine
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
Drug: Decitabine
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
Other Name: Dacogen

Experimental: Decitabine+VPA
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks, and VPA (p.o.) from day 6 of first cycle continuously throughout all treatment cycles
Drug: Decitabine
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
Other Name: Dacogen

Drug: VPA
VPA starting on day 6 of first cycle continuously throughout all treatment cycles
Other Name: Valproic acid

Experimental: Decitabine+ATRA
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks and ATRA (45 mg/m² p.o.) from day 6 to day 28 of each treatment cycle
Drug: Decitabine
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
Other Name: Dacogen

Drug: ATRA
ATRA (45 mg/m² p.o.) from day 6 to day 28 of each treatment cycle
Other Name: All-trans retinoic acid

Experimental: Decitabine+VPA+ATRA
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks and VPA (p.o.) from day 6 continuously throughout all treatment cycles and ATRA (45 mg/m² p.o.), from day 6 to day 28 of each treatment cycle
Drug: Decitabine
i.v. Decitabine 20 mg/m² over 1h, 5 days (total dose 100 mg/m²), repeated every 4 weeks
Other Name: Dacogen

Drug: VPA
VPA starting on day 6 of first cycle continuously throughout all treatment cycles
Other Name: Valproic acid

Drug: ATRA
ATRA (45 mg/m² p.o.) from day 6 to day 28 of each treatment cycle
Other Name: All-trans retinoic acid




Primary Outcome Measures :
  1. Objective best response rate (complete remission (CR) and partial remission (PR)) [ Time Frame: 12 months after randomization of the last patient ]

Secondary Outcome Measures :
  1. Overall best response rate (CR, PR and antileukemic effect (ALE)) [ Time Frame: 12 months after randomization of the last patient ]
  2. progression-free survival (PFS) [ Time Frame: 12 months after randomization of the last patient ]
  3. overall survival (OS) [ Time Frame: 12 months after randomization of the last patient ]
  4. quality of life [ Time Frame: until 4 weeks after study drug intake ]
  5. safety and toxicity [ Time Frame: until 4 weeks after study drug intake ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent obtained according to international guidelines and local law;
  2. Male or female patients aged > 60 years without upper age limit;
  3. Patients with primary or secondary AML according to WHO (≥ 20% blasts in the peripheral blood (pB) or bone marrow (BM)) who are not expected to benefit from standard remission-induction chemotherapy;
  4. Patients with < 30 000 leukocytes/μl;
  5. Performance status ECOG 0, 1, 2;
  6. Creatinine < 2.0 mg/dl (unless leukemia-related);
  7. Ability to understand the nature of the study and the study related procedures and to comply with them.

Exclusion Criteria:

  1. AML of FAB subtype M3;
  2. Previous remission-induction chemotherapy for MDS or AML, previous allografting;
  3. Previous treatment with DAC, 5-azacytidine, VPA or another HDAC inhibitor, or ATRA;
  4. "Low-dose" chemotherapy (e.g. hydroxyurea, cytosine arabinoside (Ara-C), melphalan, clofarabine etc.) within 4 weeks prior to DAC treatment, except for cytoreduction of leukocytosis ≥ 30 000/μl with hydroxyurea or Ara-C as proscribed by the study protocol (section 7.3 and 7.4); the patient must have recovered from all clinically relevant reversible non-hematologic toxicities;
  5. Treatment with tyrosine kinase inhibitors, immunomodulating agents (IMIDS) or other investigational AML treatment within the last 4 weeks or in a time period of drug half-life x 5 (whatever is shorter) before the first administration of DAC;
  6. Treatment with cytokines within previous 4 weeks;
  7. Concomitant therapy which is considered relevant for the evaluation of efficacy or safety of the trial drug (i.e. other chemo- or immunotherapy);
  8. Other malignancy requiring treatment (previous chemotherapy for other malignancies is not an exclusion criteria);
  9. Cardiac insufficiency NYHA IV;
  10. Insufficient hepatic function (bilirubin, AST or ALT > = 2.5 x Upper Limit of Normal (ULN)) (unless leukemia-related);
  11. Fatal hepatic function disorder during treatment with valproic acid in siblings;
  12. Hepatic porphyria;
  13. Manifest serious pancreatic function disorder;
  14. Plasmatic coagulation disorder not related to AML;
  15. Known active hepatitis B or C;
  16. Known HIV infection;
  17. Other uncontrolled active infections;
  18. Known allergy against soy beans or peanuts;
  19. Psychiatric disorder that interferes with treatment;
  20. Patient without legal capacity who is unable to understand the nature, significance and consequences of the study;
  21. Known hypersensitivity to, or intolerance of, one of the trial drugs, another retinoid or the excipients of the trial drugs;
  22. Concomitant use of any other investigational drug or participation in a clinical trial within the last thirty days before the start of this study; simultaneous participation in registry and diagnostic trials is allowed;
  23. Female patients who are pregnant or breast feeding;
  24. Fertile patients refusing to use safe contraceptive methods during the study (for details see clinical trial protocol section 5.3);
  25. Known or persistent abuse of medication, drugs or alcohol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00867672


Locations
Show Show 27 study locations
Sponsors and Collaborators
University Hospital Freiburg
Investigators
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Principal Investigator: Michael Lübbert, MD, PhD Department of Hematology/Oncology, University of Freiburg Medical Center

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Michael Luebbert, Professor, University Hospital Freiburg
ClinicalTrials.gov Identifier: NCT00867672    
Other Study ID Numbers: 00332/AMLSG14-09
First Posted: March 24, 2009    Key Record Dates
Last Update Posted: August 31, 2016
Last Verified: August 2016
Keywords provided by Michael Luebbert, University Hospital Freiburg:
Acute Myeloid Leukemia
Low-dose Decitabine
Valproic acid
All-trans retinoic acid
Older Patients
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Decitabine
Tretinoin
Valproic Acid
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Anticonvulsants
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Keratolytic Agents
Dermatologic Agents