NCT02172872

"InDACtion" vs "3+7" Induction in AML

10-day Decitabine Versus Conventional Chemotherapy ("3+7") Followed by Allografting in AML Patients ≥ 60 Years: a Randomized Phase III Study of the EORTC Leukemia Group, CELG, GIMEMA and German MDS Study Group

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 606 (actual)
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC · Network
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

Older patients with acute myeloid leukemia (AML) have a small (\< 10%) chance of long-term survival. Despite the treatment of elderly AML patients with intensive chemotherapy, the survival has not been improved during the last decades. The purpose of this study is to determine whether frontline therapy with a 10-day decitabine schedule provides a better survival than standard intensive combination chemotherapy in elderly AML patients (\>= 60 years).

Detailed description

* The overall survival (OS) of older AML patients has not been improved during the last decades with intensive chemotherapy based on cytarabine combined with an anthracycline ("3+7"). * Next generation sequencing technology reveals that mutations in genes involved in epigenetics are frequently mutated in AML (e.g. DNMT3a), suggesting an important role of epigenetics in the pathophysiology of AML. Decitabine (given in a 5-day schedule) has been shown to be superior to low-dose Ara-C. * A retrospective analysis revealed that epigenetic therapy (either azacitidine or decitabine) is associated with similar survival rates as intensive chemotherapy in older patients (n=671) with newly diagnosed AML. * The recently published encouraging phase 2 data with the 10-day decitabine schedule suggests that decitabine results in similar CR rates compared with intensive chemotherapy. Allogeneic transplantation (alloHCT) also offers the opportunity for cure among older AML patients, therefore treatment strategies should aim to allograft older AML patients. * Decitabine treatment can lead to very interesting cure rates when used as "bridging" to allografting. Based on the data summarized above, we hypothesize that decitabine at a daily dose of 20 mg/m² starting with the 10-day schedule followed by an alloHCT or by continuation of 5-days decitabine cycles is superior to conventional intensive chemotherapy in older AML patients.

Conditions

• Acute Myeloid Leukemia (AML)

Interventions

Type	Name	Description
DRUG	standard combination chemotherapy	1. Cycle 1 1. daunorubicin (60 mg/m²) infusion (15-30 min) for 3 days 2. cytarabine (200 mg/m²) continuous infusion (24 hrs) for 7 days. 2. Cycle 2 1. daunorubicin (45 mg/m²) infusion (15-30 min) for 3 days 2. cytarabine (200 mg/m²) continuous infusion (24 hrs) for 7 days. 3. Cycle 3 (mini-ICE) 1. idarubicin (8 mg/m²) infusion (15-30 min) for 3 days 2. cytarabine (100 mg/m²) continuous infusion (24 hrs) for 5 days 3. etoposide (100 mg/m²) infusion (1 hr) for 3 days 4. Cycle 4 (mini-ICE) (optional) 1. idarubicin (8 mg/m²) infusion (15-30 min) for 3 days 2. cytarabine (100 mg/m²) continuous infusion (24 hrs) for 5 days 3. etoposide (100 mg/m²) infusion (1 hr) for 3 days
DRUG	decitabine	1. Cycle 1: decitabine (20 mg/m²) infusion (1 hr) for 10 days 2. Cycle 2 1. if bone marrow (BM) blasts \< 5%: decitabine (20 mg/m²) infusion (1 hr) for 5 days 2. if BM blasts \>= 5%: decitabine (20 mg/m²) infusion (1 hr) for 10 days 3. Cycle 3 1. if BM blasts \< 5%: decitabine (20 mg/m²) infusion (1 hr) for 5 days 2. if BM blasts \>= 5%: decitabine (20 mg/m²) infusion (1 hr) for 10 days 4. Cycle 4-6: decitabine (20 mg/m²) infusion (1 hr) for 5 days 5. Continuation therapy from Cycle 7 and until 'progression or toxicity': decitabine (20 mg/m²) infusion (1 hr) for 5 days or 3 days Note: All patients considered eligible for transplant should be consolidated with alloHCT once donor is available.

Timeline

• Start date: 2014-11-28
• Primary completion: 2022-03-07
• Completion: 2023-12-01
• First posted: 2014-06-24
• Last updated: 2023-02-15

Locations

53 sites across 9 countries: Belgium, Bulgaria, Croatia, France, Germany, Italy, Lithuania, Netherlands, Portugal