Trial record 17 of 23 for:
Recruiting, Not yet recruiting, Available Studies | "Severe Combined Immunodeficiency"
Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases (BOLT+BMT)
This study is currently recruiting participants.
Verified June 2017 by Paul Szabolcs, University of Pittsburgh
Information provided by (Responsible Party):
Paul Szabolcs, University of Pittsburgh
First received: April 26, 2013
Last updated: June 21, 2017
Last verified: June 2017
The purpose of this study is to determine whether bilateral orthotopic lung transplantation (BOLT) followed by cadaveric partially-matched hematopoietic stem cell transplantation (HSCT) is safe and effective for patients aged 5-40 years with primary immunodeficiency (PID) and end-stage lung disease.
Severe Combined Immunodeficiency (SCID)
Immunodeficiency With Predominant T-cell Defect, Unspecified
Severe Chronic Neutropenia
Chronic Granulomatous Disease (CGD)
Hyper IgE Syndromes
Hyper IgM Deficiencies
Mendelian Susceptibility to Mycobacterial Disease
Common Variable Immune Deficiency (CVID)
Biological: CD3/CD19 negative allogeneic hematopoietic stem cells
||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
||Bilateral Orthotopic Lung Transplant in Tandem With CD3+ and CD19+ Cell Depleted Bone Marrow Transplant From Partially HLA-Matched Cadaveric Donors
Primary Outcome Measures:
- Safety: Transplant-related mortality [ Time Frame: Within 2 years of HSCT ]
Continued enrollment without exceeding the stopping rules as determined by observing the cumulative incidence of transplant related mortality.
- Safety: Engraftment failure [ Time Frame: Within 2 years of HSCT ]
Continued enrollment without exceeding the stopping rules as determined by observing the cumulative incidence of engraftment failure.
- Efficacy: Pulmonary status [ Time Frame: 6 months post HSCT ]
Absence of radiographic pneumonia
- Efficacy: Pulmonary status (late effect) [ Time Frame: 5 years post HSCT ]
Continued freedom from oxygen supplementation. We will continue to follow the subjects for late effects according to clinical standards for the rest of their life
- Efficacy: Immunologic status [ Time Frame: By 2 years post HSCT ]
- Attaining independence from treatment dose or prophylactic systemic antibiotics
- Correction of underlying immune deficiency
Secondary Outcome Measures:
Other Outcome Measures:
- Evaluation of Immune Reconstitution [ Time Frame: 5 years from HSCT ]
- Evaluation of tolerance to both the host and pulmonary graft [ Time Frame: Within 5 years of HSCT ]
- Evaluation of long term complications of solid organ transplant and hematopoietic stem cell transplant [ Time Frame: Within 5 years of HSCT ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||June 2019 (Final data collection date for primary outcome measure)
All patients will receive allogeneic hematopoietic stem cells from partially HLA-matched donors. Prior to transplantation, the marrow will be negatively selected for CD3/CD19 using a CliniMACS® depletion device.
INTERVENTION: CD3/CD19 negative allogeneic hematopoietic stem cells
Biological: CD3/CD19 negative allogeneic hematopoietic stem cells
Negative selection for CD3/CD19 will be performed on a CliniMACS® depletion device within 48 hours of collection and given at time no less that 6 weeks post lung transplant.
This is an original IND for an investigator initiated phase I/II study. The primary purpose of the study is to evaluate the safety and efficacy of performing bilateral orthotopic lung transplantation (BOLT) followed by cadaveric, partially HLA-matched CD3+/CD19+-depleted hematopoietic stem cell transplantation (HSCT) from the same donor for patients with primary immunodeficiency diseases (PID) and end-stage lung disease. For many patients with primary immunodeficiencies, HSCT is a curative, life-saving therapy, resulting in restoration of function in the immune system. Patients with primary immunodeficiencies often develop pulmonary complications as a result of chronic or recurrent infections, making them ineligible for HSCT due to the high risk of mortality and pulmonary complications. Lung transplant prior to HSCT would allow for restoration of pulmonary function prior to HSCT, allowing PID patients to proceed to HSCT, which would be curative for the patient's underlying immunodeficiency. As a secondary aim after successful engraftment with donor bone marrow, there is realistic hope for tolerating planned withdrawal of immunosuppression achieving eventual freedom from all immunosuppressive drugs and attaining a tolerant state.
|Ages Eligible for Study:
||5 Years to 40 Years (Child, Adult)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
- Patients should be between the ages of 5 and 40 years
Patients should have evidence of an underlying primary immunodeficiency for which HSCT is clinically indicated.
o Examples of such diseases include, but are not limited to:
- Severe Combined Immunodeficiency
- Combined immunodeficiency with defects in T-cell-mediated immunity, including Omenn syndrome and DiGeorge Syndrome
- Severe Chronic Neutropenia
- Chronic Granulomatous Disease
- Hyper IgE Syndrome or Job Syndrome
- CD40 or CD40L deficiency
- Wiskott-Aldrich Syndrome
- Mendelian Susceptibility to Mycobacterial Disease
- NOTE: A genetic diagnosis is recommended, but not required.
- Patients should have evidence of end-stage lung disease and be candidates for bilateral orthotopic lung transplant as determined by the lung transplant team.
- Patients <5 or >40 years of age
- Patients who have underlying malignant conditions
- Patients who have non-malignant conditions not requiring hematopoietic stem cell transplantation.
- Patients who do not meet criteria for bilateral orthotopic lung transplant
- GFR less than 50 mL/min/1.73 m2
- AST, ALT >4x upper limit of normal, Bilirubin > 2.5 mg/dL
- Cardiac ejection fraction < 40% or shortening fraction < 26%
- HIV positive by serology or PCR, HTLV positive by serology, HepBsAg positive, or HCV RNA positive by PCR
- Pregnancy or nursing mother
- Allergy to DMSO or any other ingredient used in the manufacturing of the stem cell product
- Uncontrolled infection NOTE: Pulmonary colonization with multiple organisms is common, and will not be considered an exclusion criterion.
- Any comorbid illnesses that would otherwise preclude participation
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01852370
|Children's Hospital of Pittsburgh of UPMC
|Pittsburgh, Pennsylvania, United States, 15224 |
University of Pittsburgh
||Paul Szabolcs, MD
||Division of BMT and Cellular Therapy, Children's Hospital of Pittsburgh of UPMC
||Paul Szabolcs, Chief, Division of Blood and Marrow Transplant, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh
History of Changes
|Other Study ID Numbers:
|Study First Received:
||April 26, 2013
||June 21, 2017
|Individual Participant Data (IPD) Sharing Statement:
|Plan to Share IPD:
Keywords provided by Paul Szabolcs, University of Pittsburgh:
Bone Marrow Transplantation
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on August 22, 2017
Severe Combined Immunodeficiency
Immunologic Deficiency Syndromes
Granulomatous Disease, Chronic
Common Variable Immunodeficiency
Immune System Diseases
Phagocyte Bactericidal Dysfunction
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Gram-Positive Bacterial Infections