Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01966367
Other study ID # AAAL0156
Secondary ID
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date March 2013
Est. completion date February 2030

Study information

Verified date June 2024
Source Columbia University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study's goal is to determine the frequency and severity of acute graft versus host disease, to evaluate incidence of primary and secondary graft rejection, to assess event free survival and overall survival, to determine the time to neutrophil and platelet engraftment, to determine the time to immune reconstitution (including normalization of T, B and natural killer (NK) cell repertoire and Immunoglobulin G production), and to establish the incidence of infectious complications including bacterial, viral, fungal and atypical mycobacterial and other infections following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant from a family member or unrelated adult donor for a non-malignant disease.


Description:

Graft-versus-host disease (GVHD) is a condition that results from a reaction of transplanted donor T-lymphocytes against the body and organs of the patient receiving the transplanted cells. There are two forms: acute (early) and chronic (late). Acute GVHD may produce skin rashes, liver disease, diarrhea, and an increased risk of infection. Chronic GVHD can appear in patients without prior acute GVHD. Chronic GVHD may also produce skin rashes, liver disease, diarrhea and an increased risk of infection. GVHD can make patients very sick, and have GVHD can make it more likely that patients will not survive their transplant. In this study, the investigators are offering to treat the donor peripheral blood stem cells in the hope that it will make it less likely for the patient who receives them from having GVHD. Patients on this study are being offered an experimental treatment involving the use of the CliniMACS® Reagent System (Miltenyi Biotec, Germany), a CD34+ selection device to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD. CD34+ stem cells are selected from the donor's peripheral blood stem cells. In doing this, T-cells are also removed. T-cells are the cells which are responsible for graft versus host disease (GVHD). This study is a clinical trial for patients diagnosed with a non-malignant disease who will receive a peripheral blood stem cell transplant. Patients with the following types of non-malignant diseases can participate in this study: Bone marrow failure syndromes (including Severe Aplastic Anemia, Severe Congenital Neutropenia, Amegakaryocytic Thrombocytopenia (Kostmann's Syndrome), Diamond-Blackfan Anemia, Schwachman Diamond Syndrome, Primary Immunodeficiency Syndromes, Acquired Immunodeficiency Syndromes, and Histiocytic Disorders) and Hemoglobinopathies (including Sickle Cell Anemia and Sickle/Beta Thalassemia). Patients on this study will be given standard transplant therapy with either high doses of chemotherapy drugs or lower doses of chemotherapy drugs, depending on their disease. Diseases within each disease group will receive chemotherapy that is standard for that condition. Some patients on this study will receive an allogeneic stem cell transplant (AlloSCT) from a matched related donor. If a patient does not have a matched related donor, a bone marrow search will be done at all of the bone marrow banks in the world. The patient will then go on to receive an AlloSCT from either a partially matched family member or an unrelated adult stem cell transplant donor. The transplanted cells will allow all the normal parts of the patient's blood system to recover. The experimental portion of this treatment involves the use of a Miltenyi CliniMACS CD34+ selection device to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD. CD34+ stem cell selection AlloSCT has been studied in adults with the malignant and non-malignant disease with successful engraftment and has shown some improvement in GVHD. It is unknown if CD34+ stem cell selection will work to prevent severe GVHD in children and adolescents.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 37
Est. completion date February 2030
Est. primary completion date February 2030
Accepts healthy volunteers No
Gender All
Age group N/A to 40 Years
Eligibility Inclusion Criteria: - General Eligibility (All Patients) - Patient must be < or = 40 years of age. Patients with sickle cell anemia must be at least 2 years of age. - Patient or the patient's legally authorized guardian must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign an informed consent in accordance with the institutional policies approved by the U.S. Department of Health and Human Services. - Approval for the use of this treatment protocol by the individual institution's Human Rights Committee must be obtained, in accordance with the institutional assurance policies of the U. S. Department of Health and Human Services. - Human leukocyte antigen (HLA) typing will be performed by high-resolution molecular DNA typing for HLA Class I A, B, and C and HLA Class II DRB1 and DQB1 alleles. - Unrelated donor: An 8/10, 9/10 or 10/10 matched unrelated adult donor (MUD) will be required for study entry. - Related Donor: A 5/10, 6/10, 7/10, 8/10, 9/10 or 10/10 matched (or partially matched) family donor will be required for study entry. - Non-malignant Disorders per protocol. - Hemoglobinopathies per protocol. - Requirement for CD34+ stem cell selection for a second infusion of stem cells following an allogeneic stem cell transplant from a related or unrelated adult donor. - Additional eligibility for patients with non-malignant disorders receiving myeloablative conditioning - Adequate renal function as determined by the institutional normal range. - Adequate liver function per protocol. - Adequate cardiac function defined by radionucleotide angiogram or echocardiogram. - Adequate pulmonary function by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% on room air. - Additional eligibility for patients with non-malignant disorders receiving reduced intensity conditioning - Adequate renal function as determined by the institutional normal range. - Adequate liver function per protocol. - Adequate cardiac function per protocol. - Adequate pulmonary function per protocol. Exclusion Criteria: - Patients with documented uncontrolled infection at the time of study entry are not eligible. - Pregnancy/Breast-Feeding Females who are pregnant or breast feeding at the time of study entry are not eligible. -- The following additional exclusion criteria for patients with sickle cell anemia the following exclusion criteria also apply - Patients with bridging fibrosis or cirrhosis of the liver. - Uncontrolled bacterial, viral or fungal infection in the past month. - Seropositivity for HIV. - Patients who have received prior hematocrit (HCT) within three months of enrollment for reduced intensity regimen and within six months for myeloablative regimen/reduced toxicity regimens.

Study Design


Related Conditions & MeSH terms

  • Acquired Immunodeficiency Syndrome
  • Acquired Immunodeficiency Syndromes
  • Amegakaryocytic Thrombocytopenia
  • Anemia
  • Anemia, Aplastic
  • Anemia, Diamond-Blackfan
  • Anemia, Sickle Cell
  • beta-Thalassemia
  • Bone Marrow Failure Disorders
  • Bone Marrow Failure Syndrome
  • Diamond-Blackfan Anemia
  • Familial Hemophagocytic Lymphocytosis
  • Hemoglobinopathies
  • Histiocytic Syndrome
  • Histiocytosis
  • Histiocytosis, Langerhans-Cell
  • HIV Infections
  • Immunologic Deficiency Syndromes
  • Langerhans Cell Histiocytosis (LCH)
  • Lymphocytosis
  • Lymphohistiocytosis
  • Lymphohistiocytosis, Hemophagocytic
  • Macrophage Activation Syndrome
  • Neutropenia
  • Pancytopenia
  • Primary Immunodeficiency Diseases
  • Primary Immunodeficiency Syndromes
  • Schwachman Diamond Syndrome
  • Severe Aplastic Anemia
  • Severe Congenital Neutropenia
  • Shwachman-Diamond Syndrome
  • Sickle Cell Disease
  • Sickle Cell-beta-thalassemia
  • Syndrome
  • Thalassemia
  • Thrombocytopenia

Intervention

Biological:
CD34 Stem Cell Selection Therapy
The CliniMACS (PLUS) Reagent System (Miltenyi CliniMACS CD34+ Cell Selection Device) will be used to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic graft versus host disease (GVHD).

Locations

Country Name City State
United States Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University New York New York

Sponsors (1)

Lead Sponsor Collaborator
Diane George

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of acute graft versus host disease (GVHD) Determine the incidence and severity of acute GVHD. 100 days
Secondary Incidence of primary graft failure Quantify the incidence of primary and secondary graft failure. 1 year
Secondary Survival Rate To assess event free survival and overall survival 5 years
Secondary Time to neutrophil and platelet engraftment To determine the time to neutrophil and platelet engraftment 1 year
Secondary Time to immune reconstitution To determine the time to immune reconstitution (including normalization of T, B and NK cell repertoire and Immunoglobulin G production) 2 years
Secondary Incidence of infectious complications To establish the incidence of infectious complications including bacterial, viral, fungal and atypical mycobacterial and other infections 2 years
Secondary Incidence of secondary graft failure Quantify the incidence of primary and secondary graft failure. 1 year
See also
  Status Clinical Trial Phase
Completed NCT02227472 - Working Memory and School Readiness in Preschool-Aged Children With Sickle Cell Disease
Recruiting NCT06301893 - Uganda Sickle Surveillance Study (US-3)
Recruiting NCT04398628 - ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders
Completed NCT02522104 - Evaluation of the Impact of Renal Function on the Pharmacokinetics of SIKLOS ® (DARH) Phase 4
Recruiting NCT04688411 - An mHealth Strategy to Improve Medication Adherence in Adolescents With Sickle Cell Disease N/A
Terminated NCT03615924 - Effect of Ticagrelor vs. Placebo in the Reduction of Vaso-occlusive Crises in Pediatric Patients With Sickle Cell Disease Phase 3
Not yet recruiting NCT06300723 - Clinical Study of BRL-101 in Severe SCD N/A
Recruiting NCT03937817 - Collection of Human Biospecimens for Basic and Clinical Research Into Globin Variants
Completed NCT04134299 - To Assess Safety, Tolerability and Physiological Effects on Structure and Function of AXA4010 in Subjects With Sickle Cell Disease N/A
Completed NCT04917783 - Health Literacy - Neurocognitive Screening in Pediatric SCD N/A
Completed NCT02580565 - Prevalence of Problematic Use of Equimolar Mixture of Oxygen and Nitrous Oxide and Analgesics in the Sickle-cell Disease
Recruiting NCT04754711 - Interest of Nutritional Care of Children With Sickle Cell Disease on Bone Mineral Density and Body Composition N/A
Completed NCT04388241 - Preliminary Feasibility and Efficacy of Behavioral Intervention to Reduce Pain-Related Disability in Pediatric SCD N/A
Recruiting NCT05431088 - A Phase 2/3 Study in Adult and Pediatric Participants With SCD Phase 2/Phase 3
Completed NCT01158794 - Genes Influencing Iron Overload State
Recruiting NCT03027258 - Point-of-Delivery Prenatal Test Results Through mHealth to Improve Birth Outcome N/A
Withdrawn NCT02960503 - Macrolide Therapy to Improve Forced Expiratory Volume in 1 Second in Adults With Sickle Cell Disease Phase 1/Phase 2
Completed NCT02620488 - A Brief Laboratory-Based Hypnosis Session for Pain in Sickle Cell Disease N/A
Completed NCT02567682 - Drug Interaction Study of GBT440 With Caffeine, S-warfarin, Omeprazole, and Midazolam in Healthy Subjects Phase 1
Not yet recruiting NCT02525107 - Prevention of Vaso-occlusive Painful Crisis by Using Omega-3 Fatty Acid Supplements Phase 3