Stem Cell Transplant (SCT) for Dyskeratosis Congenita or SAA

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00455312
• Date of registration: 30/03/2007
• Prospective Registration: Yes
• Primary sponsor: Masonic Cancer Center, University of Minnesota
• Public title: Stem Cell Transplant (SCT) for Dyskeratosis Congenita or SAA
• Scientific title: Hematopoietic Stem Cell Transplant For Patients With Dyskeratosis Congenita and Severe Aplastic Anemia
• Date of first enrolment: August 2007
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00455312
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

United States

Contacts

• Name: Jakub Tolar, M.D., Ph.D.
• Affiliation: Masonic Cancer Center, University of Minnesota

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients with dyskeratosis congenita (DC) or severe aplastic anemia (SAA) 0-70 years
of age with an acceptable hematopoietic stem cell (HSC) donor

- HSC source

- Human leukocyte antigen (HLA) identical or 1 antigen mismatched sibling or
other relative eligible to donate bone marrow (BM), umbilical cord blood
(UCB) or mobilized peripheral blood (PB) at cell doses that meet current
institutional standards.

- HLA identical or up to a 1 antigen mismatched unrelated donor.

- Two units of unrelated umbilical cord blood (UCB) that are (a) up to 2 HLA
antigens mismatched to the patient (b) up to 2 HLA antigens mismatched to
each other, (c) minimum cell dose of = 3.5 x 10^7 nucleated cells/kg and
optimal cell dose = 5 x 10^7 nucleated cells/kg.

- If two units are not available: single unrelated UCB unit selected according
to Minnesota Bone Marrow Transplant (BMT) program guidelines

- Disease Characteristics for DC (both of the following):

- Evidence of BM failure:

- Requirement for red blood cell and/or platelet transfusions,

- Requirement for granulocyte colony-stimulating factor (G-CSF) or
granulocyte-macrophage colony-stimulating factor (GM-CSF) or
erythropoietin, or

- Refractory cytopenias defined as two out of three: platelets
<40,000/microliter (uL) or transfusion dependent, Absolute neutrophil
count <500/uL without hematopoietic growth factor support, Hemoglobin
<9g/uL or transfusion dependent

- Diagnosis of DC:

- A triad of mucocutaneous features: oral leukoplakia, nail dystrophy,
abnormal reticular skin hyperpigmentation.

- Or one of the following: Short telomeres (under a research study),
Dyskerin mutation, Telomerase RNA (TERC) mutation

- Disease Characteristics for SAA (both of the following):

- Evidence of BM failure:

- Refractory cytopenia defined by bone marrow cellularity <25-50% (with <
30% residual hematopoietic cells)

- Diagnosis of SAA:

- Refractory cytopenias defined as two out of three: Platelets <20,000/uL
or transfusion dependent, Absolute neutrophil count <500/uL without
hematopoietic growth factor support, Absolute reticulocyte count
<20,000/uL

- Patients with early myelodysplastic features.

- Patients with or without clonal cytogenetic abnormalities.

Patient Exclusion Criteria:

- Patients with one or more of the following:

- Decompensated congestive heart failure; left ventricular ejection fraction <35%

- Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on
biopsy

- Carbon Monoxide Diffusing Capacity (DLCO) <30% predicted, and oxygen requirement

- Glomerular filtration rate (GFR) <30% predicted

- Pregnant or lactating female

- Active serious infection whereby patient has been on intravenous antibiotics for
at least one week prior to study entry. Any patient with AIDS or HIV
seropositivity. If recent mold infection e.g. Aspergillus - must have >30 days of
appropriate treatment before HSC transplantation and infection must be controlled
and cleared by the Infectious Disease consultant.

- Cannot receive total body irradiation (TBI) due to prior radiation therapy

- Diagnosis of Fanconi anemia based on diepoxybutane (DEB).

- DC patients with advanced myelodysplastic syndrome (MDS) or acute myeloid
leukemia with >30 blasts.

- History of non hematopoietic malignancy within 2 years except resected basal cell
carcinoma or treated carcinoma in situ.



Age minimum: N/A
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Dyskeratosis Congenita

Aplastic Anemia

Intervention(s)

Drug: Fludarabine

Procedure: Stem Cell Transplantation

Drug: antithymocyte globulin

Drug: Methylprednisolone

Procedure: Total Body Irradiation

Drug: Cyclophosphamide

Drug: Campath 1H

Primary Outcome(s)

Neutrophil Engraftment [Time Frame: Day 100]

Secondary Outcome(s)

Incidence of Late Secondary Malignancies [Time Frame: 1 Year]

Incidence of Chronic GVHD [Time Frame: 1 year]

Incidence of Chronic GVHD [Time Frame: 6 months]

Incidence of Regimen Related Mortality at 100 Days [Time Frame: 100 days]

Incidence of Grade 3-4 Acute Graft Versus Host Disease (GVHD) [Time Frame: Day 100]

Incidence of Pulmonary Complications [Time Frame: 6 Months]

Incidence of Grade 2-4 Acute Graft Versus Host Disease (GVHD) [Time Frame: Day 100]

Overall Survival [Time Frame: Day 100]

Overall Survival [Time Frame: 1 Year]

Secondary ID(s)

MT2006-06

0612M98727

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 31/05/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00455312