Stem Cell Transplant (SCT) for Dyskeratosis Congenita or SAA

NCT00455312 | Completed Phase 2 Results DMC

• 2 other identifiers: MT2006-060612M98727
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Dyskeratosis Congenita; Aplastic Anemia

Keywords

Dyskeratosis Congenita; Hematopoietic Stem Cell Transplantation; Severe Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

• Neutrophil Engraftment

  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 hematopoietic cell transplantation.

  Day 100

Secondary Outcomes (9)

• Incidence of Regimen Related Mortality at 100 Days

  100 days

• Incidence of Chronic GVHD

  6 months

• Incidence of Chronic GVHD

  1 year

• Incidence of Late Secondary Malignancies

  1 Year

• Incidence of Grade 2-4 Acute Graft Versus Host Disease (GVHD)

  Day 100

Study Arms (2)

Patients with DC

EXPERIMENTAL

Patients with dyskeratosis congenita (DC). Patients are treated with alemtuzumab (Campath 1H), Cyclophosphamide, Fludarabine, total body irradiation and stem cell transplantation.

Drug: Campath 1H; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Total Body Irradiation; Procedure: Stem Cell Transplantation

Patients with SAA

EXPERIMENTAL

Patients with severe aplastic anemia (SAA). Patients are treated with alemtuzumab (Campath 1H), Cyclophosphamide, Fludarabine, antithymocyte globulin, total body irradiation and stem cell transplantation.

Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Total Body Irradiation; Procedure: Stem Cell Transplantation; Drug: antithymocyte globulin; Drug: Methylprednisolone

Interventions

Campath 1H DRUG

10, 9, 8, 7, and 6 days before transplant subjects will be given 1 dose of campath 1H given via catheter (0.2 mg/kg over 2 hours).

Also known as: Alemtuzumab

Patients with DC

Cyclophosphamide DRUG

7 days before the transplant, 1 dose of cyclophosphamide is given via catheter (50mg/kg IV over 2 hours).

Also known as: Cytoxan

Patients with DC; Patients with SAA

Fludarabine DRUG

6, 5, 4, 3, and 2 days before the transplant, 1 dose fludarabine is given via catheter (40 mg/kg IV over 1 hour)

Also known as: Fludara

Patients with DC; Patients with SAA

Total Body Irradiation PROCEDURE

1 day before the transplant one dose (200 cGy) of total body irradiation is given

Also known as: Radiation therapy, therapeutic radiation

Patients with DC; Patients with SAA

Stem Cell Transplantation PROCEDURE

Infusion of stem cells on Day 0.

Also known as: Bone Marrow Transplant

Patients with DC; Patients with SAA

antithymocyte globulin DRUG

ATG (rabbit) 3 mg/kg for 3 days.

Also known as: Atgam, Thymoglobulin, ATG

Patients with SAA

Methylprednisolone DRUG

2mg/kg IV is given before each dose of antithymocyte globulin (ATG).

Patients with SAA

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):

You may not qualify if:

• 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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• Dietz AC, Orchard PJ, Baker KS, Giller RH, Savage SA, Alter BP, Tolar J. Disease-specific hematopoietic cell transplantation: nonmyeloablative conditioning regimen for dyskeratosis congenita. Bone Marrow Transplant. 2011 Jan;46(1):98-104. doi: 10.1038/bmt.2010.65. Epub 2010 Apr 12.

  PMID: 20383216 DERIVED

MeSH Terms

Conditions

Dyskeratosis Congenita; Anemia, Aplastic

Interventions

Alemtuzumab; Cyclophosphamide; fludarabine; fludarabine phosphate; Whole-Body Irradiation; Radiotherapy; Stem Cell Transplantation; Bone Marrow Transplantation; Antilymphocyte Serum; thymoglobulin; Methylprednisolone

Condition Hierarchy (Ancestors)

Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Anemia

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Therapeutics; Investigative Techniques; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Tissue Transplantation; Immune Sera; Biological Products; Complex Mixtures; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Jakub Tolar, MD
• Organization: Masonic Cancer Center, University of Minnesota

tolar003@umn.edu

Study Officials

• Jakub Tolar, M.D., Ph.D.

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2007
• First Posted: April 3, 2007
• Study Start: August 1, 2007
• Primary Completion: March 1, 2015
• Study Completion: June 1, 2016
• Last Updated: December 5, 2017
• Results First Posted: May 31, 2017

Record last verified: 2017-12

Locations

US (1)