Trial Outcomes & Findings for Bendamustine and Idarubicin in Treating Older Patients With Previously Untreated AML or MDS (NCT NCT01141725)

Last Updated: 2017-08-18

Results Overview

Assessed by cytogenetics/fluorescence in situ hybridization (FISH) and flow cytometry of blood and bone marrow samples. The response criteria defined by Cheson et al. will be used in this study. These criteria are: morphologic leukemia-free state; morphologic complete remission (CR); cytogenetic CR (CRc); molecular CR (CRm); morphologic CR with incomplete blood count recovery (CRi); partial remission (PR); treatment failure; recurrence (progressive disease).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

39 participants

Primary outcome timeframe

6 months

Results posted on

2017-08-18

Participant Flow

Participant milestones

Participant milestones
Measure	Bendamustine Dose of 45mg/m2/Day Patients receive bendamustine hydrochloride 45mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Bendamustine Dose of 60mg/m2/Day Patients receive bendamustine hydrochloride 60mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Bendamustine Dose of 75mg/m2/Day Patients receive bendamustine hydrochloride 75mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	3	33	3
Overall Study COMPLETED	3	33	3
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bendamustine and Idarubicin in Treating Older Patients With Previously Untreated AML or MDS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Combination Chemotherapy) n=39 Participants Patients receive bendamustine hydrochloride IV on days 1-5 and idarubicin IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. bendamustine hydrochloride: Given IV idarubicin: Given IV
Age, Continuous	73 years n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Region of Enrollment United States	39 participants n=5 Participants
ECOG ECOG 0	0 Participants n=5 Participants
ECOG ECOG 1	35 Participants n=5 Participants
ECOG ECOG 2	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Treatment A n=3 Participants Patients receive bendamustine hydrochloride 45mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Treatment B n=33 Participants Patients receive bendamustine hydrochloride 60mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Treatment C n=3 Participants Patients receive bendamustine hydrochloride 75mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Response CR	0 Participants	10 Participants	1 Participants
Response CRi	0 Participants	2 Participants	0 Participants
Response No CR	3 Participants	21 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to day +100 after end of therapy or until the patient received an alternative treatment for leukemia, whatever happens earlier

Toxicities will be graded using the National Cancer Institute (NCI) Common Toxicity Criteria version 3.0.

Outcome measures

Outcome measures
Measure	Treatment A n=3 Participants Patients receive bendamustine hydrochloride 45mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Treatment B n=33 Participants Patients receive bendamustine hydrochloride 60mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Treatment C n=3 Participants Patients receive bendamustine hydrochloride 75mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Incidence of Greater Than or Equal to Grade 3 Toxicity	0 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: 6 months

A bayesian approach to estimate the MTD of bendamustine associated with a CR rate of at least 40% and with \<30% grade 3-4 non-haematological toxicity was used (Wathen et al, 2008).The MTD of bendamustine in combination with idarubicin was determined after two cases of grade 3 toxicity were noted in the three patients entered at the 75 mg/m2 dose. The DLTs were congestive heart failure and mucositis in one patient each. Patients subsequent to this were treated at the 60 mg/m2 bendamustine dose.

Outcome measures

Outcome measures
Measure	Treatment A n=39 Participants Patients receive bendamustine hydrochloride 45mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Treatment B Patients receive bendamustine hydrochloride 60mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Treatment C Patients receive bendamustine hydrochloride 75mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Maximum Tolerated Dose	60 mg/m2	—	—

PRIMARY outcome

Timeframe: 5 years

In a five year following, the median survival was obtained.

Outcome measures

Outcome measures
Measure	Treatment A n=39 Participants Patients receive bendamustine hydrochloride 45mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Treatment B Patients receive bendamustine hydrochloride 60mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Treatment C Patients receive bendamustine hydrochloride 75mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Median Survival	7.2 months Interval 1.0 to 22.0	—	—

SECONDARY outcome

Timeframe: 5 years

Population: Data for this Outcome Measure was not collected per dose level and is unavailable.

In a five year following, the disease free survival was obtained.

Outcome measures

Outcome measures
Measure	Treatment A n=39 Participants Patients receive bendamustine hydrochloride 45mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Treatment B Patients receive bendamustine hydrochloride 60mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Treatment C Patients receive bendamustine hydrochloride 75mg/m2 IV on days 1-5 and idarubicin 12mg/m2 IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Disease-free Survival (DFS)	235 days Interval 83.0 to 277.0	—	—

Adverse Events

Treatment (Combination Chemotherapy)

Serious events: 29 serious events

Other events: 0 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Combination Chemotherapy) n=39 participants at risk Patients receive bendamustine hydrochloride IV on days 1-5 and idarubicin IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. bendamustine hydrochloride: Given IV idarubicin: Given IV Adverse event report was not collected by dose level.
Blood and lymphatic system disorders Febrile Neutropenia	74.4% 29/39 • Number of events 29 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Infections and infestations Fungal infection	10.3% 4/39 • Number of events 4 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Respiratory, thoracic and mediastinal disorders Pneumonia	5.1% 2/39 • Number of events 2 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Skin and subcutaneous tissue disorders Cellulitis	5.1% 2/39 • Number of events 2 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Infections and infestations Bacteraemia	5.1% 2/39 • Number of events 2 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Infections and infestations Sepsis	5.1% 2/39 • Number of events 2 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Infections and infestations Sinusitis	2.6% 1/39 • Number of events 1 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Blood and lymphatic system disorders Platelet transfusion refractory	2.6% 1/39 • Number of events 1 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Cardiac disorders Heart Failure	2.6% 1/39 • Number of events 1 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Cardiac disorders Atrial Fibrillation	2.6% 1/39 • Number of events 1 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Infections and infestations Severe mucositis	2.6% 1/39 • Number of events 1 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Blood and lymphatic system disorders Intracranial bleeding	2.6% 1/39 • Number of events 1 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Infections and infestations Clostridium difficile infection	2.6% 1/39 • Number of events 1 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.6% 1/39 • Number of events 1 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
General disorders Dehydration	2.6% 1/39 • Number of events 1 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.
Renal and urinary disorders Acute renal injury	2.6% 1/39 • Number of events 1 • 6 months Other (Not Including Serious) Adverse Events were not collected/assessed.

Other adverse events

Adverse event data not reported

Additional Information

Elihu Estey, MD, Director of AML Program

FHCRC/UWMC

Phone: 206-288-7176

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place