Clinical Trial: SCT for Dyskeratosis Congenita or SAA

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

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

Detailed Summary:

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.


Sponsor: Masonic Cancer Center, University of Minnesota

Current Primary Outcome: Neutrophil Engraftment [ Time Frame: Day 100 ]

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.


Original Primary Outcome: Demonstrates sustained engraftment after fludarabine-based preparative regimen and allogenic hematopoietic stem cell transplantation in patients with DC.

Current Secondary Outcome:

  • Incidence of Regimen Related Mortality at 100 days [ Time Frame: 100 days ]
    all deaths without previous relapse or progression
  • Incidence of Chronic GVHD [ Time Frame: 6 months and 1 year ]
    Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
  • Incidence of Late Secondary Malignancies [ Time Frame: 1 Year ]
    Defined as patients who have a secondary malignancy (cancer) occurring.
  • Incidence of grade 2-4 and 3-4 acute graft versus host disease (GVHD) [ Time Frame: Day 100 ]
    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
  • Overall Survival [ Time Frame: Day 100 and 1 Year ]
    Overall survival is defined as time from date of transplant to date of death or censored at the date of last documented contact for patients still alive.
  • Incidence of Pulmonary Complications [ Time Frame: 6 Months ]
    Defined as patients who exhibit a pulmonary (lung) adverse event.


Original Secondary Outcome:

  • Determine the incidence of regimen related mortality at 100 days; incidence of grade 2-4 and 3-4 acute graft versus host disease (GVHD) at 100 days;
  • incidence of chronic GVHD at 6 months and 1 year; overall survival at 100 days and 1 year;
  • immune reconstitution at 100 days, 6 months, and 1 year;
  • incidence of pulmonary complications and secondary malignancies at any time point.


Information By: Masonic Cancer Center, University of Minnesota

Dates:
Date Received: March 30, 2007
Date Started: August 2007
Date Completion: November 2016
Last Updated: January 21, 2016
Last Verified: January 2016