A Phase 2 Trial to Evaluate the Efficacy and Safety of OCV-501 in Elderly Patients With Acute Myeloid Leukemia

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01961882
• Collaborator: Korea Otsuka Pharmaceutical Co., Ltd. (Industry)
• Enrollment: 134
• Locations: 14
• Arms: 2
• Duration (Months): 49.5
• Patients Per Site: 9.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To compare disease-free survival in patients 60 years or older with acute myeloid leukemia (AML) who are randomly assigned to receive either OCV-501 monotherapy or placebo.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: OCV-501; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 134 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Trial to Evaluate the Efficacy and Safety of OCV-501 in Elderly Patients With Acute Myeloid Leukemia
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Nov 16, 2017
• Actual Study Completion Date: Nov 16, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OCV-501 arm	Drug: OCV-501
Placebo Comparator: Placebo arm	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Disease-Free Survival [2 years (treatment period)]

   Disease-free survival (DFS) was defined as the time from randomization until relapse or death from any cause, whichever came first, by the DFS-cutoff date.

Secondary Outcome Measures

1. Overall Survival [2 years (treatment period)]

   Subjects were surveyed for survival by the date of cutoff. The cutoff date was set as the date after 728 days (2 years) from the day that the last subject started IMP administration.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with AML who achieved first complete remission within one or two courses of standard induction therapy, and completed standard consolidation therapy (more than one course).

• Patients who are 60 years or older.

• Patients who have provided written informed consent within 90 days from the last dose of consolidation therapy on an informed consent form that has been approved by an institutional review board or independent ethics committee.

Exclusion Criteria:

• Patients who have acute promyelocytic leukemia (APL) with t(15;17) (q22;q12), (PML/RARA) karyotype abnormalities, and other variant types.

• Patients who are scheduled for hematopoietic stem cell transplantation.

• Patients who have received drugs potentially affecting the immune system within 4 weeks before starting IMP administration or who may receive such drugs after start of the trial.

• Patients who have a severe concurrent disease or psychiatric illness likely to interfere with participation in this trial.

• Patients who are HIV antibody positive, HBV-DNA positive or have unrecovered chronic hepatitis C with positive HCV antibody.

• Patients who have cirrhosis.

• Patients judged to be ineligible by the investigator (or subinvestigator) for any other reasons.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chubu Region		Japan
2		Chugoku Region		Japan
3		Hokkaido Region		Japan
4		Kanto Region		Japan
5		Kinki Region		Japan
6		Kyushu Region		Japan
7		Shikoku Region		Japan
8		Tohoku Region		Japan
9		Daegu		Korea, Republic of
10		Seoul		Korea, Republic of
11		Kaoshiung		Taiwan
12		Taichung		Taiwan
13		Tainan		Taiwan
14		Taipei		Taiwan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.
• Korea Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Jun-ichi Hashimoto, PhD, Otsuka Pharmaceutical Co., Ltd.

Study Documents (Full-Text)

• Study Protocol - Jul 7, 2015
• Statistical Analysis Plan - Jan 9, 2018

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01961882
• Other Study ID Numbers: 311-12-001; JapicCTI-142429
• First Posted: Oct 14, 2013
• Last Update Posted: Mar 26, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by Otsuka Pharmaceutical Co., Ltd.: OCV-501; Acute Myeloid Leukemia; Antigen specific cancer immunotherapeutic
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute

Study Results

Participant Flow

Pre-assignment Detail	Of the 134 subjects randomized in this trial, one subject who was randomized but did not receive the investigational medicinal product (IMP) was excluded from all analysis data sets.

Arm/Group Title	OCV-501	Placebo
Arm/Group Description	3 mg of OCV-501 (0.4 mL) was administered subcutaneously, once-weekly up to the 8th administration, and once every 2 weeks from the 9th administration onward.	Placebo (0.4 mL) was administered subcutaneously, once-weekly up to the 8th administration, and once every 2 weeks from the 9th administration onward.
Period Title: Overall Study
STARTED	69	65
COMPLETED	19	23
NOT COMPLETED	50	42

Baseline Characteristics

Arm/Group Title	OCV-501	Placebo	Total
Arm/Group Description	3 mg of OCV-501 (0.4 mL) was administered subcutaneously, once-weekly up to the 8th administration, and once every 2 weeks from the 9th administration onward.	Placebo (0.4 mL) was administered subcutaneously, once-weekly up to the 8th administration, and once every 2 weeks from the 9th administration onward.	Total of all reporting groups
Overall Participants	68	65	133
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 27.9%	18 27.7%	37 27.8%
>=65 years	49 72.1%	47 72.3%	96 72.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.3 (5.61)	68.6 (6.20)	68.4 (5.89)
Sex: Female, Male (Count of Participants)
Female	22 32.4%	30 46.2%	52 39.1%
Male	46 67.6%	35 53.8%	81 60.9%
Race/Ethnicity, Customized (Count of Participants)
Asian	68 100%	65 100%	133 100%
Region of Enrollment (Count of Participants)
South Korea	9 13.2%	9 13.8%	18 13.5%
Japan	52 76.5%	53 81.5%	105 78.9%
Taiwan	7 10.3%	3 4.6%	10 7.5%

Outcome Measures

1. Primary Outcome

Title	Disease-Free Survival
Description	Disease-free survival (DFS) was defined as the time from randomization until relapse or death from any cause, whichever came first, by the DFS-cutoff date.
Time Frame	2 years (treatment period)

Outcome Measure Data

Analysis Population Description

FAS: all subjects who received the IMP at least once and from whom data on at least 1 efficacy endpoint were obtained after the start of IMP administration.

Arm/Group Title	OCV-501	Placebo
Arm/Group Description	3 mg of OCV-501 (0.4 mL) was administered subcutaneously, once-weekly up to the 8th administration, and once every 2 weeks from the 9th administration onward.	Placebo (0.4 mL) was administered subcutaneously, once-weekly up to the 8th administration, and once every 2 weeks from the 9th administration onward.
Measure Participants	68	65
Number (95% Confidence Interval) [percentage of participants]	40.9 60.1%	41.4 63.7%

2. Secondary Outcome

Title	Overall Survival
Description	Subjects were surveyed for survival by the date of cutoff. The cutoff date was set as the date after 728 days (2 years) from the day that the last subject started IMP administration.
Time Frame	2 years (treatment period)

Outcome Measure Data

Analysis Population Description

FAS: all subjects who received the IMP at least once and from whom data on at least 1 efficacy endpoint were obtained after the start of IMP administration.

Arm/Group Title	OCV-501	Placebo
Arm/Group Description	3 mg of OCV-501 (0.4 mL) was administered subcutaneously, once-weekly up to the 8th administration, and once every 2 weeks from the 9th administration onward.	Placebo (0.4 mL) was administered subcutaneously, once-weekly up to the 8th administration, and once every 2 weeks from the 9th administration onward.
Measure Participants	68	65
Number (95% Confidence Interval) [percentage of participants]	60.3 88.7%	58.5 90%

Adverse Events

Time Frame	Treatment-emergent adverse events were collected from the first dose of IMP to post-treatment observation (up to 17 days after the last dose of IMP or within 7 days from withdrawal judgment).
Arm/Group Title	OCV-501		Placebo
Arm/Group Description	3 mg of OCV-501 (0.4 mL) was administered subcutaneously, once-weekly up to the 8th administration, and once every 2 weeks from the 9th administration onward.		Placebo (0.4 mL) was administered subcutaneously, once-weekly up to the 8th administration, and once every 2 weeks from the 9th administration onward.
All Cause Mortality
	OCV-501		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/68 (1.5%)		1/65 (1.5%)
Serious Adverse Events
	OCV-501		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/68 (10.3%)		7/65 (10.8%)
Blood and lymphatic system disorders
Febrile neutropenia	0/68 (0%)		1/65 (1.5%)
Cardiac disorders
Stress cardiomyopathy	1/68 (1.5%)		0/65 (0%)
Eye disorders
Retinal detachment	1/68 (1.5%)		0/65 (0%)
General disorders
Multiple organ dysfunction syndrome	1/68 (1.5%)		1/65 (1.5%)
Hepatobiliary disorders
Cholecystitis	0/68 (0%)		1/65 (1.5%)
Hepatitis acute	0/68 (0%)		1/65 (1.5%)
Immune system disorders
Drug hypersensitivity	1/68 (1.5%)		0/65 (0%)
Hypersensitivity	1/68 (1.5%)		0/65 (0%)
Infections and infestations
Infectious colitis	1/68 (1.5%)		0/65 (0%)
Sepsis	1/68 (1.5%)		0/65 (0%)
Upper respiratory tract infection	1/68 (1.5%)		0/65 (0%)
Pneumonia	0/68 (0%)		1/65 (1.5%)
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome	0/68 (0%)		1/65 (1.5%)
Nervous system disorders
Hypoglycaemic encephalopathy	0/68 (0%)		1/65 (1.5%)
Respiratory, thoracic and mediastinal disorders
Organising pneumonia	0/68 (0%)		1/65 (1.5%)
Vascular disorders
Orthostatic hypotension	0/68 (0%)		1/65 (1.5%)
Other (Not Including Serious) Adverse Events
	OCV-501		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	67/68 (98.5%)		59/65 (90.8%)
Blood and lymphatic system disorders
Thrombocytopenia	4/68 (5.9%)		3/65 (4.6%)
Cardiac disorders
Atrial fibrillation	0/68 (0%)		4/65 (6.2%)
Gastrointestinal disorders
Diarrhoea	7/68 (10.3%)		5/65 (7.7%)
Stomatitis	2/68 (2.9%)		7/65 (10.8%)
General disorders
Injection site induration	50/68 (73.5%)		19/65 (29.2%)
Injection site erythema	31/68 (45.6%)		11/65 (16.9%)
Injection site pruritus	20/68 (29.4%)		9/65 (13.8%)
Injection site pain	18/68 (26.5%)		2/65 (3.1%)
Pyrexia	10/68 (14.7%)		4/65 (6.2%)
Injection site swelling	7/68 (10.3%)		2/65 (3.1%)
Malaise	6/68 (8.8%)		2/65 (3.1%)
Oedema peripheral	3/68 (4.4%)		4/65 (6.2%)
Infections and infestations
Nasopharyngitis	18/68 (26.5%)		13/65 (20%)
Upper respiratory tract infection	6/68 (8.8%)		7/65 (10.8%)
Herpes zoster	4/68 (5.9%)		3/65 (4.6%)
Pharyngitis	2/68 (2.9%)		6/65 (9.2%)
Bronchitis	1/68 (1.5%)		4/65 (6.2%)
Injury, poisoning and procedural complications
Contusion	2/68 (2.9%)		4/65 (6.2%)
Investigations
Platelet count decreased	7/68 (10.3%)		9/65 (13.8%)
Neutrophil count decreased	1/68 (1.5%)		5/65 (7.7%)
Musculoskeletal and connective tissue disorders
Back pain	8/68 (11.8%)		3/65 (4.6%)
Pain in extremity	5/68 (7.4%)		2/65 (3.1%)
Myalgia	4/68 (5.9%)		1/65 (1.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Headache	5/68 (7.4%)		2/65 (3.1%)
Psychiatric disorders
Insomnia	2/68 (2.9%)		4/65 (6.2%)
Respiratory, thoracic and mediastinal disorders
Cough	5/68 (7.4%)		2/65 (3.1%)
Skin and subcutaneous tissue disorders
Rash	8/68 (11.8%)		8/65 (12.3%)
Urticaria	4/68 (5.9%)		1/65 (1.5%)
Pruritus	3/68 (4.4%)		4/65 (6.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.