Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01319851
• Date of registration: 15/09/2010
• Prospective Registration: No
• Primary sponsor: Emory University
• Public title: Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
• Scientific title: Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation for Children With Non-Malignant Diseases Who Have Been Multiply Transfused: a Pilot Study
• Date of first enrolment: September 2010
• Target sample size: 3
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01319851
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: N/A

Countries of recruitment

United States

Contacts

• Name: John Horan, MD
• Affiliation: Emory University/Children's Healthcare of Atlanta

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Must be between the ages of 0-21 years at the time of admission for transplant

2. Must have been transfused with at least five platelet, erythrocyte or granulocyte
units (partial or full)

3. Must have one of the following diseases:

(a) hemoglobin SS or hemoglobin SB Sß0 thalassemia and meet one of the criteria below
for having severe sickle cell disease (i) Previous central nervous system event
lasting longer than 24 hours, plus objective imaging evidence of CNS vasculopathy,
with or without residual neurologic findings (ii) Frequent (= 3 per year for 2 years)
painful vaso-occlusive episodes (defined as episode lasting = 4 hours and requiring
hospitalization or outpatient treatment with parenteral opioids/opiates). Must have
also (iii) Recurrent (= 3 in lifetime) acute chest syndrome events which have
necessitated exchange transfusion or chronic transfusion therapy. (iv) Any combination
of = 3 acute chest syndrome episodes and vasoocclusive pain episodes (defined as
above) yearly for 3 years. (v) Stage I or II sickle lung disease (see appendix 1) (vi)
Pulmonary hypertension, measured by tricuspid regurgitant jet velocity (TRV) of
greater than 2.5m/s (vii) Osteonecrosis involving multiple joints. (viii) Sickle Cell
nephropathy with moderately severe renal insufficiency estimated GFR =30 ml/min, but
=60 ml/min/1.73 m2 (Requires evaluation by a nephrologist). (b) Thalassemia major (c)
Glanzmann thrombasthenia (d) Wiskott-Aldrich syndrome (e) Chronic-granulomatous
disease (f) Severe congenital neutropenia (g) Leukocyte adhesion deficiency (h)
Shwachman-Diamond syndrome (i) Diamond-Blackfan anemia (j) Fanconi anemia (k)
Dyskeratosis-congenita (l) Chediak-Higashi syndrome (m) Acquired (immune;
non-inherited, non-congenital) severe aplastic anemia (only patients whose best graft
source is a mismatched related donor, unrelated marrow donor or cord blood unit) (n)
Other inherited or congenital marrow failure syndromes complicated by severe aplastic
anemia (o) Other inherited or congenital red blood cell disorders requiring monthly
chronic transfusion therapy. (p) Other inherited or congenital platelet disorders
resulting in at least three inpatient hospitalizations in the past two years for
bleeding. (q) Other inherited or congenital granulocyte disorders resulting in at
least three inpatient hospitalizations in the past two years for infection.

4. Must have an available HLA identical sibling (HLA matched related), a non-HLA
identical parent or sibling who is matched at least seven of eight loci (mismatch can
be at an allele or antigen level), an unrelated adult donor who is matched at least
seven of eight loci (mismatch can be at an allele or antigen level) or an unrelated
cord blood unit that is matched at five of six loci (A (antigen level), B (antigen
level), DRB1 (allele level)) and provides a minimum pre-cryopreservation TNC dose of
5.0 x 107 TNC/kg recipient weight.

Exclusion Criteria:

1. Hemophagocytic lymphohistiocytosis or other disorder characterized by NK cell
dysfunction, since alefacept's effect is mediated by NK cells.

2. Biopsy proven cirrhosis (score IV).

3. SCD chronic lung disease = stage III (see appendix 1)

4. Severe renal dysfunction defined as estimated GFR of <30 ml/min.

5. Severe cardiac dysfunction defined as shortening fraction < 25%.

6. Severe neurologic impairment other than hemiplegia alone, defined as full scale IQ =
70, quadriplegia or paraplegia, inability to ambulate, inability to communicate
without assistive device, or any impairment resulting in decline of Lansky performance
score to <50%.

7. Karnofsky or Lansky functional performance score < 50%

8. Confirmed HIV seropositivity.

9. Patient with unspecified chronic toxicity serious enough to detrimentally affect the
patient's capacity to tolerate bone marrow transplantation.

10. Patient or patient's guardian(s) unable to understand the nature and risks inherent in
the BMT process.

11. History of lack of compliance with medical care that would jeopardize transplant
course.

12. Patient is pregnant or lactating

13. Donor who for psychological, physiologic, or medical reasons is unable to tolerate a
bone marrow harvest or receive general anesthesia.

14. Donor is HIV infected.

15. Donor is pregnant

16. Hemoglobin SS, or hemoglobin Sß0 thalassemia patient who is eligible for one of the
two trials of myeloablative conditioning currently being conducted by the Aflac Center
(SALT: Alternate-Donor Bone Marrow and Cord Blood Transplantation for Children with
High-Risk Sickle Cell Disease Busulfan, fludarabine, ATG and Reduced-Dose
Cyclophosphamide Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation
in Patients with Severe Sickle Cell Disease: a pilot study

17. Patients with thalassemia major who are eligible for any multicenter study we are
participating in.

18. Patients whose best graft source is a related or unrelated donor/cord blood unit that
is mismatched and the patient's HLA antibody testing (see below) demonstrates an
antibody directed against the disparate HLA molecule.



Age minimum: N/A
Age maximum: 21 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diamond-Blackfan Anemia

Schwachman-Diamond Syndrome

Dyskeratosis-congenita

Sickle Cell Disease

Severe Aplastic Anemia

Glanzmann Thrombasthenia

Leukocyte Adhesion Deficiency

Chediak-Higashi Syndrome

Severe Congenital Neutropenia

Chronic-granulomatous Disease

Fanconi Anemia

Thalassemia

Wiskott-Aldrich Syndrome

Intervention(s)

Drug: Alefacept

Primary Outcome(s)

Feasibility of Alefacept Pre-conditioning, Measured by Number of Subjects With Full Donor Engraftment [Time Frame: Two years post-transplant]

Secondary Outcome(s)

Number of Participants Who Experienced Acute Graft-versus-host Disease (aGVHD), Measured by NIH Consensus Criteria (NCC) Score: Grade II-IV [Time Frame: Day 30 post-transplant]

Number of Participants Who Experienced Chronic Graft-versus-host Disease (cGVHD), Measured by the NIH Criteria Consensus (NCC) [Time Frame: Day 100 post-transplant]

Incidence of Greater Than or Equal to 85% CD3 Donor Chimerism [Time Frame: Day 30 post-transplant]

Number of Participants That Expressed Grade 2 or 3 Regimen-Related Toxicity [Time Frame: Day 42 post-transplant]

Incidence of 100% CD33 Donor Chimerism [Time Frame: Day 30 post-transplant]

Number of Participants That Expressed Successful Neutrophil Engraftment [Time Frame: Day 100 post-transplant]

Secondary ID(s)

IRB00039680

BMT Alefacept

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Children's Healthcare of Atlanta

Results

• Results available: Yes
• Date Posted: 09/03/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01319851