Clinical trial NCT01877837: Stem Cell Transplantation for Sickle Cell Anemia
Official title: Reduced Intensity Matched Sibling Bone Marrow Transplantation for Sickle Cell Anemia in Patients 2-30 Years Old
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sickle Cell Disease
Keywords: Stem cell transplant
Sickle cell
Stem cell transplantation
Related
Unrelated
Lead sponsor: Hackensack Meridian Health
Sponsor class: OTHER
First posted: 2013-06-14
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This protocol will be investigating the use of stem cell transplantation, in related donors, to cure sickle cell disease. Sickle cell disease is a recessive disorder caused by a point mutation that results in the substitution of valine for glutamic acid at the sixth position in the B-chain of hemoglobin. This leads to sickling of the red blood cells under many conditions, such as hypoxia, dehydration, and hyperthermia. The sickling leads to vaso-occlusion, which causes irreversible damage in almost all systems in the body, including the central nervous system (CNS), lungs, heart, bones, eyes, liver, and kidneys.

Detailed description: Primary objective:

1) To determine disease free survival (DFS) at two years after matched sibling transplant using bone marrow (BM) after a conditioning regimen consisting of distal timed Alemtuzumab, Fludarabine, and Melphalan for patients 2-30 y/o

Secondary objectives:

1. Overall survival
2. Rate of neutrophil and platelet engraftment for BM
3. Incidence of graft failure
4. Incidence of grade II-IV and grade III-IV acute graft vs host disease (GVHD)
5. Incidence of chronic GVHD
6. Incidence of other transplant complications, such as veno-occlusive disease, central nervous system (CNS) toxicity, and idiopathic pneumonia syndrome (IPS)
7. Incidence of reactivation of CMV, EBV, adenovirus, BK/JC virus
8. Incidence of invasive fungal disease
9. Time to immune reconstitution via monitoring of lymphocyte subpopulations and immunoglobulin levels

Eligibility criteria: Inclusion Criteria:

* Patient Eligibility

  1) Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single or double) with a total TNC dose of greater than 5 x 107/kg recipient weight)
  1. Age 2-30
  2. Hb SS, S-thal0, S-thal+, SC
  3. Evidence of ongoing hemolysis: Hb\<10, retic \>5%, LDH \> 500, TB\>2
  4. Karnofsky/Lansky score \>50
  5. LVSF\>26% or LVEF\>40%
  6. DLCO \>40% or O2 sat \>85% for those patients that can't perform PFTs
  7. GFR \>70 and serum creatinine \< 1.5 \* ULN for age
  8. ALT and AST \< 5 x ULN, direct bilirubin \<2 x ULN
  9. If the patient has been on chronic transfusion or has a ferritin \>1000, liver biopsy should be done and show no evidence of bridging fibrosis or cirrhosis
* Exclusion criteria

  1. Evidence of uncontrolled bacterial, viral, or fungal infection within one month prior to initiation of the conditioning regimen
  2. Pregnant or breastfeeding
  3. HIV positive
  4. Written informed consent not obtained

Primary outcomes:
measure: Number of Participants With Graft Failure
timeFrame: 2 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
Study officials:
affiliation: Hackensack Meridian Health
name: Jennifer Krajewski, MD
role: PRINCIPAL_INVESTIGATOR
References: