Trial Outcomes & Findings for Low Dose Melphalan and Bortezomib for AML and High-Risk MDS (NCT NCT00789256)

NCT ID: NCT00789256

Last Updated: 2018-10-24

Results Overview

Determine disease response to treatment using Cheson 2000 report of an international working group to standardize response criteria for myelodysplastic syndromes.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 26 participants
• Primary outcome timeframe: Post Cycle 1 through 28 days post-treatment
• Results posted on: 2018-10-24

Participant Flow

Recruitment for this study was open at Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center - Manchester (NH), White River Junction Veteran's Administration Medical Center, and Integrated Community Oncology Network - Florida.

The intention was to accrue 13 evaluable patients for the initial stages of this study. For each strata, if there were no responders within the first 13 patients, the study would statistically rule-out a response rate of 20% or more with p = 0.05. If there were any responders, the study would accrue an additional 11 evaluable patients.

Participant milestones

Measure	Strata 1 Includes patients who have not seen prior medical intervention for their disease. Patients assigned to Strata 1 will receive Melphalan 2mg orally, once daily and Bortezomib 1.0 mg/M2 IV on days 1, 4, 8, 11.	Strata 2 Includes patients who have received prior medical intervention for their disease. Patients assigned to Strata 2 will receive Melphalan 2mg orally, once daily and Bortezomib 1.0 mg/M2 IV on days 1, 4, 8, 11.
Overall Study STARTED	14	12
Overall Study COMPLETED	14	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Low Dose Melphalan and Bortezomib for AML and High-Risk MDS

Baseline characteristics by cohort

Measure	Strata 1 n=14 Participants Group 1 will include patients who have not seen prior medical intervention for their disease.	Strata 2 n=12 Participants will include patients who have received prior medical intervention for their disease.	Total n=26 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Age, Categorical >=65 years	14 Participants n=5 Participants	7 Participants n=7 Participants	21 Participants n=5 Participants
Age, Continuous	73 years STANDARD_DEVIATION 4.53 • n=5 Participants	68 years STANDARD_DEVIATION 9.07 • n=7 Participants	71 years STANDARD_DEVIATION 7.69 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	12 participants n=7 Participants	26 participants n=5 Participants

PRIMARY outcome

Timeframe: Post Cycle 1 through 28 days post-treatment

Determine disease response to treatment using Cheson 2000 report of an international working group to standardize response criteria for myelodysplastic syndromes.

Outcome measures

Measure	Strata 1 n=14 Participants Group 1 will include patients who have not seen prior medical intervention for their disease.	Strata 2 n=12 Participants will include patients who have received prior medical intervention for their disease.
Response Rate of the Combination of Bortezomib and Melphalan in Patients With AML and High-risk MDS.	5 participants	2 participants

SECONDARY outcome

Timeframe: Start of treatment through 28 days post-treatment

The safety profile is based on the number of adverse events experienced by participants as reported in the Adverse Events results section for this protocol.

Outcome measures

Measure	Strata 1 n=26 Participants Group 1 will include patients who have not seen prior medical intervention for their disease.	Strata 2 will include patients who have received prior medical intervention for their disease.
Determine Safety Profile of the Combination of Bortezomib and Melphalan. Reported adverse events	24 Participants	—
Determine Safety Profile of the Combination of Bortezomib and Melphalan. Without reportable adverse event	2 Participants	—

SECONDARY outcome

Timeframe: Pre-treatment and at complete response

Population: No data was collected and these results were not obtained. The collaborating laboratory with the capability to perform the assay with leukemic cells was not available to analyze the samples.

Leukemic cells will be collected to test the presence of the study drugs using a cell viability assay in vitro and in vivo.

Outcome measures

Outcome data not reported

Adverse Events

Strata 1

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Strata 2

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Strata 1 n=14 participants at risk Group 1 will include patients who have not seen prior medical intervention for their disease.	Strata 2 n=12 participants at risk will include patients who have received prior medical intervention for their disease.
Infections and infestations Febrile neutropenia	7.1% 1/14 • Number of events 1	0.00% 0/12
Infections and infestations Legionella Pneumonia	0.00% 0/14	8.3% 1/12 • Number of events 1
Nervous system disorders CNS Hemorrhage	0.00% 0/14	8.3% 1/12 • Number of events 1
Cardiac disorders Myocardial Infarction	0.00% 0/14	8.3% 1/12 • Number of events 1

Other adverse events

Measure	Strata 1 n=14 participants at risk Group 1 will include patients who have not seen prior medical intervention for their disease.	Strata 2 n=12 participants at risk will include patients who have received prior medical intervention for their disease.
Blood and lymphatic system disorders Neutropenia	71.4% 10/14 • Number of events 10	50.0% 6/12 • Number of events 6
Blood and lymphatic system disorders Thrombocytopenia	71.4% 10/14 • Number of events 10	58.3% 7/12 • Number of events 7
Blood and lymphatic system disorders Anemia	35.7% 5/14 • Number of events 5	25.0% 3/12 • Number of events 3
Respiratory, thoracic and mediastinal disorders Dyspnea	14.3% 2/14 • Number of events 2	0.00% 0/12
Infections and infestations Pneumonia	14.3% 2/14 • Number of events 2	25.0% 3/12 • Number of events 3
Infections and infestations Urinary Tract Infection	7.1% 1/14 • Number of events 1	0.00% 0/12
Skin and subcutaneous tissue disorders Rash	0.00% 0/14	8.3% 1/12 • Number of events 1
Infections and infestations Zoster reactivation	7.1% 1/14 • Number of events 1	0.00% 0/12
Infections and infestations Infection NOS	7.1% 1/14 • Number of events 1	0.00% 0/12
Cardiac disorders Atrial fibrillation	14.3% 2/14 • Number of events 2	0.00% 0/12
Infections and infestations Cellulitis	0.00% 0/14	8.3% 1/12 • Number of events 1
Infections and infestations Febrile neutropenia	21.4% 3/14 • Number of events 3	8.3% 1/12 • Number of events 1
Metabolism and nutrition disorders Hypokalemia	0.00% 0/14	8.3% 1/12 • Number of events 1
General disorders Fatigue	7.1% 1/14 • Number of events 1	0.00% 0/12
General disorders Generalized weakness	7.1% 1/14 • Number of events 1	0.00% 0/12
Blood and lymphatic system disorders Pancytopenia	7.1% 1/14 • Number of events 1	0.00% 0/12
Nervous system disorders Neuropathy	7.1% 1/14 • Number of events 1	0.00% 0/12

Additional Information

Marc Gautier, MD - Principal Investigator

Dartmouth-Hitchcock Medical Center

Phone: 603-650-5529

Email: marc.gautier@hitchcock.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place