Trial Outcomes & Findings for Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation (NCT NCT01319851)

Results Overview

All subjects received alefacept prior to hematopoietic stem cell transplantation and were followed up to at least two years after transplantation to ensure successful engraftment.

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

3 participants

Primary outcome timeframe

Two years post-transplant

Results posted on

2017-07-27

Participant Flow

Patients were enrolled at the Aflac Cancer and Blood Disorders Center within Children's Healthcare of Atlanta (CHOA) from November 2010 to November 2011.

One subject with Fanconi Anemia (FA) received fludarabine (Flu) 25 mg/m2 on days -10 to -5 and cyclophosphamide (Cy) 10 mg/kg on days -5 to -2. The other two subjects received Flu 25 mg/m2 on days -6 to -1, Cy 50 mg/kg on day -2, and low-dose total body irradiation(TBI; 200 cGy) on day -1.

Participant milestones

Participant milestones
Measure	Alefacept Pediatric subjects with non-malignant diseases (NMD) received pre-conditioning with alefacept 0.5 mg/kg/dose i.v. with the first dose split on days -40 and -39 and the remaining doses given on days -33, -26, -19, and -12 (e.g. weekly for 5 doses).
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alefacept n=3 Participants Pediatric subjects with non-malignant diseases (NMD) received pre-conditioning with alefacept 0.5 mg/kg/dose i.v. with the first dose split on days -40 and -39 and the remaining doses given on days -33, -26, -19, and -12 (e.g. weekly for 5 doses).
Age, Categorical <=18 years	3 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	7 years STANDARD_DEVIATION 3.54 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Two years post-transplant

All subjects received alefacept prior to hematopoietic stem cell transplantation and were followed up to at least two years after transplantation to ensure successful engraftment.

Outcome measures

Outcome measures
Measure	Alefacept n=3 Participants Pediatric subjects with non-malignant diseases (NMD) received pre-conditioning with alefacept 0.5 mg/kg/dose i.v. with the first dose split on days -40 and -39 and the remaining doses given on days -33, -26, -19, and -12 (e.g. weekly for 5 doses).
Feasibility of Alefacept Pre-conditioning, Measured by Number of Subjects With Full Donor Engraftment	3 participants

SECONDARY outcome

Timeframe: Day 42 post-transplant

Regimen-related toxicity was measured using the Bearman criteria. The Bearman criteria grades toxicity levels at Grade 1, Grade 2, Grade 3, and Grade 4. In this system, grade I toxicity is reversible without treatment and grade 2 is not life threatening, but requires treatment. Grade 3 requires life-support intervention and grade 4 is fatal. All regimen-related toxicities were determined to be unlikely attributable to the study drug.

Outcome measures

Outcome measures
Measure	Alefacept n=3 Participants Pediatric subjects with non-malignant diseases (NMD) received pre-conditioning with alefacept 0.5 mg/kg/dose i.v. with the first dose split on days -40 and -39 and the remaining doses given on days -33, -26, -19, and -12 (e.g. weekly for 5 doses).
Number of Participants That Expressed Grade 2 or 3 Regimen-Related Toxicity	2 participants

SECONDARY outcome

Timeframe: Day 100 post-transplant

Neutrophil engraftment was assessed with absolute neutrophils \>500\*10\^8/kg by 100 days post transplant. Neutrophils were counted by performing a complete blood cell count (CBC).

Outcome measures

Outcome measures
Measure	Alefacept n=3 Participants Pediatric subjects with non-malignant diseases (NMD) received pre-conditioning with alefacept 0.5 mg/kg/dose i.v. with the first dose split on days -40 and -39 and the remaining doses given on days -33, -26, -19, and -12 (e.g. weekly for 5 doses).
Number of Participants That Expressed Successful Neutrophil Engraftment	3 participants

SECONDARY outcome

Timeframe: Day 30 post-transplant

CD3 chimerism was measured from peripheral blood lymphocytes 30 days post transplant. DNA chimerism analysis was performed by amplified fragment length polymorphism.

Outcome measures

Outcome measures
Measure	Alefacept n=3 Participants Pediatric subjects with non-malignant diseases (NMD) received pre-conditioning with alefacept 0.5 mg/kg/dose i.v. with the first dose split on days -40 and -39 and the remaining doses given on days -33, -26, -19, and -12 (e.g. weekly for 5 doses).
Incidence of Greater Than or Equal to 85% CD3 Donor Chimerism	3 participants

SECONDARY outcome

Timeframe: Day 30 post-transplant

CD33 chimerism was measured from peripheral blood lymphocytes 30 days post transplant. DNA chimerism analysis was performed by amplified fragment length polymorphism.

Outcome measures

Outcome measures
Measure	Alefacept n=3 Participants Pediatric subjects with non-malignant diseases (NMD) received pre-conditioning with alefacept 0.5 mg/kg/dose i.v. with the first dose split on days -40 and -39 and the remaining doses given on days -33, -26, -19, and -12 (e.g. weekly for 5 doses).
Incidence of 100% CD33 Donor Chimerism	3 participants

SECONDARY outcome

Timeframe: Day 30 post-transplant

Cumulative Incidence of Grade II-IV aGVHD Score at 30 Days. The NIH Consensus grading and severity criteria includes physical assessments of skin, oral cavity, eyes, gynecological and laboratory data and patient reports. Each domain is scored from Grade 0 (no involvement) to Grade IV (severe involvement).

Outcome measures

Outcome measures
Measure	Alefacept n=3 Participants Pediatric subjects with non-malignant diseases (NMD) received pre-conditioning with alefacept 0.5 mg/kg/dose i.v. with the first dose split on days -40 and -39 and the remaining doses given on days -33, -26, -19, and -12 (e.g. weekly for 5 doses).
Number of Participants Who Experienced Acute Graft-versus-host Disease (aGVHD), Measured by NIH Consensus Criteria (NCC) Score: Grade II-IV Grade II	2 participants
Number of Participants Who Experienced Acute Graft-versus-host Disease (aGVHD), Measured by NIH Consensus Criteria (NCC) Score: Grade II-IV Grade III	1 participants
Number of Participants Who Experienced Acute Graft-versus-host Disease (aGVHD), Measured by NIH Consensus Criteria (NCC) Score: Grade II-IV Grade IV	0 participants

SECONDARY outcome

Timeframe: Day 100 post-transplant

The severity criteria of chronic graft-versus-host disease (cGVHD) recommended by the NIH Criteria Consensus (NCC) was employed. The number of organs involved and the severity of the disease in these organs dictated the global summary score used to define the disease as mild, moderate, or severe. Mild disease indicates one or two organs involved each with a maximal score of 1. Moderate disease indicates three or more organs involved with a score of 2 in any individual organ, or lung involvement with a score of 1. Severe global GVHD is defined by a score of 3 in any organ, or a lung score of 2.

Outcome measures

Outcome measures
Measure	Alefacept n=3 Participants Pediatric subjects with non-malignant diseases (NMD) received pre-conditioning with alefacept 0.5 mg/kg/dose i.v. with the first dose split on days -40 and -39 and the remaining doses given on days -33, -26, -19, and -12 (e.g. weekly for 5 doses).
Number of Participants Who Experienced Chronic Graft-versus-host Disease (cGVHD), Measured by the NIH Criteria Consensus (NCC) Mild cGVHD	0 participants
Number of Participants Who Experienced Chronic Graft-versus-host Disease (cGVHD), Measured by the NIH Criteria Consensus (NCC) Moderate cGVHD	1 participants
Number of Participants Who Experienced Chronic Graft-versus-host Disease (cGVHD), Measured by the NIH Criteria Consensus (NCC) Severe cGVHD	1 participants

Adverse Events

Alefacept

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Alefacept n=3 participants at risk Pediatric subjects with non-malignant diseases (NMD) received pre-conditioning with alefacept 0.5 mg/kg/dose i.v. with the first dose split on days -40 and -39 and the remaining doses given on days -33, -26, -19, and -12 (e.g. weekly for 5 doses).
Gastrointestinal disorders Stomatitis	66.7% 2/3 • Number of events 2
Immune system disorders Chronic graft versus host disease	66.7% 2/3 • Number of events 3

Other adverse events

Other adverse events
Measure	Alefacept n=3 participants at risk Pediatric subjects with non-malignant diseases (NMD) received pre-conditioning with alefacept 0.5 mg/kg/dose i.v. with the first dose split on days -40 and -39 and the remaining doses given on days -33, -26, -19, and -12 (e.g. weekly for 5 doses).
Infections and infestations Pulmonary aspergillosis	33.3% 1/3 • Number of events 1
Infections and infestations Cytomegalovirus (CMV) Viremia	33.3% 1/3 • Number of events 1
Respiratory, thoracic and mediastinal disorders Sinusitis	33.3% 1/3 • Number of events 1
Blood and lymphatic system disorders Bacteremia	33.3% 1/3 • Number of events 1

Additional Information

Dr. John Horan

Emory University

Phone: 404-785-1272

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place