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Trial record 2 of 10 for:    paroxysmal nocturnal hemoglobinuria | Recruiting, Not yet recruiting, Available Studies | United States

Unrelated And Partially Matched Related Donor PSCT w/ TCR αβ Depletion for Patients With BMF

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ClinicalTrials.gov Identifier: NCT03047746
Recruitment Status : Recruiting
First Posted : February 9, 2017
Last Update Posted : May 8, 2017
Sponsor:
Information provided by (Responsible Party):
Timothy Olson, Children's Hospital of Philadelphia

Brief Summary:
This is a single arm pilot study using TCR alpha/beta+ T cell-depleted peripheral blood stem cells (PBSC) from closely matched unrelated donors or partially matched/haploidentical related donors for hematopoietic stem cell transplant (HSCT) in patients with acquired and inherited bone marrow failure (BMF) syndromes.

Condition or disease Intervention/treatment
Acquired Aplastic Anemia Paroxysmal Nocturnal Hemoglobinuria Inherited Bone Marrow Failure Syndromes Device: CliniMACs

Detailed Description:
This is a single arm pilot study using TCR alpha/beta+ T cell-depleted peripheral blood stem cells (PBSC) from closely matched unrelated donors or partially matched/haploidentical related donors for hematopoietic stem cell transplant (HSCT) in patients with acquired and inherited bone marrow failure (BMF) syndromes. Previously established, disease-specific transplant preparative regimens will be administered based on the specific underlying BMF condition. Mobilized PBSC will be processed using the CliniMACS system for TCR alpha/beta+ T cell depletion plus CD19+ B cell depletion. The study will determine efficacy of this strategy in terms of engraftment, rates of acute and chronic Graft versus Host Disease (GvHD), and one year overall and event-free survival.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Unrelated And Partially Matched Related Donor Peripheral Blood Stem Cell Transplantation (PSCT) With TCR αβ + T Cell And B Cell Depletion For Patients With Acquired And Inherited Bone Marrow Failure
Actual Study Start Date : February 1, 2017
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022


Arm Intervention/treatment
TCRalpha/beta Tcell Depletion for BMF with trilineage aplasia
Patients with acquired or inherited bone marrow failure (iBMF) with trilineage aplasia will be given previously established, disease-specific chemotherapy and/or radiation based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from unrelated or partially matched related donors.
Device: CliniMACs
Peripheral blood stem cells from closely matched unrelated or partially matched related donors will be processed using the CliniMACS device to remove TCRalpha/beta T cells and B cells, in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique
TCRalpha/beta Tcell Depletion for BMF w/o trilineage aplasia
Patients with acquired or inherited bone marrow failure (iBMF) without trilineage aplasia will be given previously established, disease-specific chemotherapy and/or radiation based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from unrelated or partially matched related donors.
Device: CliniMACs
Peripheral blood stem cells from closely matched unrelated or partially matched related donors will be processed using the CliniMACS device to remove TCRalpha/beta T cells and B cells, in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique



Primary Outcome Measures :
  1. Rate of graft failure [ Time Frame: Up to three years post-transplantation ]
  2. Time to neutrophil engraftment [ Time Frame: Up to 60 days post-transplantation ]
  3. Incidence of acute graft vs. host disease (GVHD) [ Time Frame: Up to 100 days post-transplantation ]
  4. Incidence of chronic graft vs. host disease (GVHD) [ Time Frame: Up to three years post-transplantation ]

Secondary Outcome Measures :
  1. Treatment-related Mortality (TRM) [ Time Frame: Up to 100 days post-transplantation ]
  2. Probability of event-free survival (EFS) [ Time Frame: Up to 1 year post-transplantation ]
  3. Probability of overall survival (OS) [ Time Frame: Up to 1 year post-transplantation ]
  4. Reactivation/Infection from CMV, EBV, adenovirus [ Time Frame: Up to 1 year post-transplantation ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Acquired and Inherited Bone Marrow Failure Conditions Associated with Trilinear Bone Marrow Failure

    • Acquired Aplastic Anemia
    • Paroxysmal Nocturnal Hemoglobinuria
    • Fanconi Anemia
    • Dyskeratosis Congenita and related telomere disorders
    • Shwachman-Diamond Syndrome
  • Inherited Bone Marrow Failure Conditions Associated with Predominant Single Lineage Failure

    • Severe Congenital Neutropenia
    • Isolated disorders of erythropoiesis
    • Congenital Thrombocytopenia Syndromes
  • Organ function status

    • Renal: Serum creatinine <1.5x upper limit of normal for age
    • Hepatic: Transaminases <5x upper limit of normal. Bilirubin <2.0 mg/dL, (unless elevation due to Gilberts disease or known hemolytic anemia).
    • Cardiac: shortening fraction >27%
    • Pulmonary: Diffusing Capacity (DLCO) >50% predicted in patients old enough to comply with pulmonary function testing (PFTs) or no baseline oxygen requirement for younger patients.
    • Lansky or Karnofsky performance >60
  • Infectious disease criteria

    • No active, untreated infections
    • Patients with likely bacterial infections must be receiving appropriate antibacterial therapy and demonstrating therapy response
    • Patients with likely fungal infections must have had at least 2 weeks of appropriate anti-fungal antibiotics and be asymptomatic.
    • Patients with symptoms consistent with active viral infection will be deferred until viral symptoms resolve. Patients with evidence of cytomegalovirus (CMV), Epstein-Barr virus (EBV) or other known viremia must receive appropriate therapy to clear viremia prior to initiating study therapy.
  • Signed consent by parent/guardian or able to give consent if >18 years

Exclusion Criteria:

  • Patients who do not meet disease, organ or infectious criteria.
  • Patients with a clinical diagnosis of myelodysplastic syndrome (MDS) defined by combination of bone marrow dysplasia and classic cytogenetic lesion (Monosomy 7, Trisomy 8 eg.), with or without excess blasts.
  • Patients with no suitable closely Human leukocyte antigen (HLA)-matched unrelated or related haploidentical matched donor available. Patients with suitable fully matched related donor are also not eligible.
  • Pregnant females. All females of childbearing potential must have negative pregnancy test.

Donor selection and eligibility:

• Donor selection will comply with 21 CFR 1271* of the U.S. Food and Drug Administration's Code of Federal Regulations

Donor testing:

  • Unrelated donor meets National Marrow Donor Program criteria for donation
  • For partially matched related donors, Children's Hospital of Philadelphia (CHOP) bone marrow transplant (BMT) standard procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases. The donor collection program accredited.
  • For partially matched related donors, if subject has genetically confirmed iBMF syndrome, related donor must be evaluated for this disorder and testing must be negative
  • Infectious disease testing of donor will be per current Blood and Marrow Transplant Program Standards of Practice as per 21 CFR Part 1271. Donor medical records and history are reviewed to confirm that the donor is free of infectious risk factors and meets donor eligibility criteria as defined by 21 CFR 127.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03047746


Contacts
Contact: Barb McGlynn, RN, BSN 215-590-1303 MCGLYNN@email.chop.edu

Locations
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Barbara McGlynn, RN, BSN       MCGLYNN@email.chop.edu   
Sub-Investigator: Nancy Bunin, MD         
Sub-Investigator: Stephan Grupp, MD, PhD         
Principal Investigator: Timothy Olson, MD, PhD         
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Timothy Olson, MD, PhD Children's Hospital of Philadelphia

Responsible Party: Timothy Olson, Timothy Olson M.D. Ph.D., Assistant Professor Pediatrics, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT03047746     History of Changes
Other Study ID Numbers: 16-012881
First Posted: February 9, 2017    Key Record Dates
Last Update Posted: May 8, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Hemoglobinuria
Hemoglobinuria, Paroxysmal
Anemia, Aplastic
Pancytopenia
Anemia
Hematologic Diseases
Bone Marrow Diseases
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Anemia, Hemolytic
Myelodysplastic Syndromes