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Hematopoietic Stem Cell Transplant For Patients With Dyskeratosis Congenita and Severe Aplastic Anemia


Phase 2/Phase 3
N/A
70 Years
Open (Enrolling)
Both
Dyskeratosis Congenita, Aplastic Anemia

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Trial Information

Hematopoietic Stem Cell Transplant For Patients With Dyskeratosis Congenita and Severe Aplastic Anemia


This is an open label, single arm, phase II clinical trial designed to evaluate the safety
and efficacy of the treatment regimen. Efficacy will be measured by long-term engraftment
of the transplanted cells.The primary endpoint of neutrophil engraftment is defined as an
absolute neutrophil count (ANC) >5 x 108/L (first of three consecutive laboratory
measurements on different days) with at least 10% donor cells by day 100. We will evaluate
the proportion of success (P) and its 95% confidence interval (CI) for the entire group.
The null hypothesis of 90% engraftment will be rejected if 4 or more patients fail to
engraft out of 15 evaluable patients. The secondary endpoints of regimen related mortality,
acute and chronic graft-versus-host disease (GVHD) and secondary malignancies will be
estimated by cumulative incidence treating non-event deaths as a competing risk. Survival
will be estimated by Kaplan-Meier methods. Immune reconstitution will be summarized with
descriptive statistics.

SAA and DC arms will be analyzed separately.


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

- 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/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, 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 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Neutrophil Engraftment

Outcome Description:

Defined as an absolute neutrophil count (ANC) >5 x 10^8/L (first of three consecutive laboratory measurements on different days) with at least 10% donor cells by day 100. Demonstrate sustained engraftment after a fludarabine based preparative regimen in patients with dyskeratosis congenita followed by HCT.

Outcome Time Frame:

Day 100

Safety Issue:

No

Principal Investigator

Jakub Tolar, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota

Authority:

United States: Institutional Review Board

Study ID:

MT2006-06

NCT ID:

NCT00455312

Start Date:

August 2007

Completion Date:

November 2014

Related Keywords:

  • Dyskeratosis Congenita
  • Aplastic Anemia
  • Dyskeratosis Congenita
  • Hematopoietic Stem Cell Transplantation
  • Severe Aplastic Anemia
  • Anemia
  • Anemia, Aplastic
  • Dyskeratosis Congenita

Name

Location

Masonic Cancer Center, University of MinnesotaMinneapolis, Minnesota  55455