Stem Cell Transplant (SCT) for Dyskeratosis Congenita or SAA
| Status: | Completed |
|---|---|
| Conditions: | Anemia |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | Any - 70 |
| Updated: | 12/7/2017 |
| Start Date: | August 2007 |
| End Date: | June 2016 |
Hematopoietic Stem Cell Transplant For Patients With Dyskeratosis Congenita and Severe Aplastic Anemia
Transplantation with stem cells is a standard therapy in many centers around the world.
Previous experience with stem cell transplantation therapy for leukemias, lymphomas, other
cancers, aplastic anemia and other non-malignant diseases, has led to prolonged disease-free
survival or cure for some patients. However, the high doses of pre-transplant radiation and
chemotherapy drugs used, and the type of drugs used, often cause many side effects that are
intolerable for some patients. Slow recovery of blood counts is a frequent complication of
high dose pre-transplant regimens, resulting in a longer period of risk for bleeding and
infection plus a longer time in the hospital.
Recent studies have shown that using lower doses of radiation and chemotherapy (ones that do
not completely kill all of the patient's bone marrow cells) before blood or bone marrow
transplant, may be a better treatment for high risk patients, such as those with Dyskeratosis
Congenita (DC) or Severe Aplastic Anemia(SAA). These low dose transplants may result in
shorter periods of low blood counts, and blood counts that do not go as low as with
traditional pre-transplant radiation and chemotherapy. Furthermore, in patients with
Dyskeratosis Congenita or SAA, the stem cell transplant will replace the blood forming cells
with healthy cells.
It has recently been shown that healthy marrow can take and grow after transplantation which
uses doses of chemotherapy and radiation that are much lower than that given to patients with
leukemia. While high doses of chemotherapy and radiation may be necessary to get rid of
leukemia, this may not be important to patients with Dyskeratosis Congenita or SAA. The
purpose of this research is to see if this lower dose chemotherapy and radiation regimen
followed by transplant is a safe and effective treatment for patients with Dyskeratosis
Congenita or SAA.
Previous experience with stem cell transplantation therapy for leukemias, lymphomas, other
cancers, aplastic anemia and other non-malignant diseases, has led to prolonged disease-free
survival or cure for some patients. However, the high doses of pre-transplant radiation and
chemotherapy drugs used, and the type of drugs used, often cause many side effects that are
intolerable for some patients. Slow recovery of blood counts is a frequent complication of
high dose pre-transplant regimens, resulting in a longer period of risk for bleeding and
infection plus a longer time in the hospital.
Recent studies have shown that using lower doses of radiation and chemotherapy (ones that do
not completely kill all of the patient's bone marrow cells) before blood or bone marrow
transplant, may be a better treatment for high risk patients, such as those with Dyskeratosis
Congenita (DC) or Severe Aplastic Anemia(SAA). These low dose transplants may result in
shorter periods of low blood counts, and blood counts that do not go as low as with
traditional pre-transplant radiation and chemotherapy. Furthermore, in patients with
Dyskeratosis Congenita or SAA, the stem cell transplant will replace the blood forming cells
with healthy cells.
It has recently been shown that healthy marrow can take and grow after transplantation which
uses doses of chemotherapy and radiation that are much lower than that given to patients with
leukemia. While high doses of chemotherapy and radiation may be necessary to get rid of
leukemia, this may not be important to patients with Dyskeratosis Congenita or SAA. The
purpose of this research is to see if this lower dose chemotherapy and radiation regimen
followed by transplant is a safe and effective treatment for patients with Dyskeratosis
Congenita or SAA.
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.
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
- 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.
We found this trial at
1
site
425 E River Pkwy # 754
Minneapolis, Minnesota 55455
Minneapolis, Minnesota 55455
612-624-2620
Masonic Cancer Center at University of Minnesota The Masonic Cancer Center was founded in 1991....
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