MiniClini: Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases

Sponsor
Children's Hospital of Philadelphia (Other)
Overall Status
Completed
CT.gov ID
NCT02277639
Collaborator
(none)
2
Enrollment
1
Location
2
Arms
52
Duration (Months)
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with CD3+ /CD19+ depleted peripheral stem cell grafts from mismatched donors. There are two conditioning regimens depending upon patient diagnosis and age.

Condition or DiseaseIntervention/TreatmentPhase
  • Device: CliniMACs device
Phase 2

Detailed Description

This study will allow transplantation using a reduced intensity conditioning regimen for children with non-malignant diseases who lack a matched related or unrelated donor. Donors will be unrelated or partially matched related, depending upon urgency and availability. If each parent is haploidentical, the mother will be preferred, as there is evidence of reduced transplant related mortality and superior survival with a maternal donor. The risks of severe graft vs host disease (GVHD) and Epstein-Barr lymphoproliferative disorder will be reduced or eliminated by T and B cell depletion using the Miltenyi Clinimacs device. Patients with bone marrow failure syndromes, who are at high risk for rejection, will undergo pre-conditioning immune suppression with Thymoglobulin. It is recommended that patients with immunedysregulation syndromes receive pre-RIC alemtuzumab as this may reduce the risk on non-engraftment and hyperinflammatory states.

Post-transplant immune suppression will be used to prevent GVHD, as CD3 depletion does not deplete as completely as CD34+ selection. It will be rapidly weaned if no GVHD by day 100 to allow immune reconstitution.

Study Design

Study Type:
Interventional
Actual Enrollment :
2 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Intervention Model Description:
Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I/II Study of Reduced Intensity Conditioning for Patients With Non-Malignant Diseases Using CD3+/CD19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells
Study Start Date :
Nov 1, 2011
Actual Primary Completion Date :
Mar 1, 2016
Actual Study Completion Date :
Mar 1, 2016

Arms and Interventions

ArmIntervention/Treatment
Experimental: Bone Marrow Failure Syndrome

Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion.

Device: CliniMACs device
Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.

Experimental: Immunodeficiency / Dysregulation

Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion.

Device: CliniMACs device
Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Engraftment [One Year]

    The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A to 22 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Bone marrow failure syndromes for which SCT is indicated, including severe aplastic anemia refractory to non transplant therapies congenital neutropenia, congenital thrombocytopenia, congenital red cell aplasia

  • Immunodeficiencies for which allogeneic hematopoietic stem cell transplant is indicated, including severe combined immunodeficiencies, Wiskott-Aldrich syndrome, IPEX syndrome, X-linked lymphoproliferative disease

  • Immune dysregulation syndromes, including refractory or recurrent hemophagocytic lymphohistiocytosis, HLH with genetic mutations, refractory multisystemic Langerhans cell histiocytosis, other MAS refractory to standard therapy

  • Organ function clearance

Exclusion Criteria:
  • Uncontrolled bacterial, viral or fungal infections

  • HLA matched related or unrelated donor able to donate mobilized peripheral stem cells.

  • Fanconi's syndrome, dyskeratosis congenita or other chromosomal fragility syndromes

  • Pregnant Females

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1The Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUnited States19104

Sponsors and Collaborators

  • Children's Hospital of Philadelphia

Investigators

  • Principal Investigator: Nancy Bunin, MD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Nancy Bunin, BMT Medical Director, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT02277639
Other Study ID Numbers:
  • 11-008330
  • CHP 980
First Posted:
Oct 29, 2014
Last Update Posted:
Apr 11, 2018
Last Verified:
Mar 1, 2018
Keywords provided by Nancy Bunin, BMT Medical Director, Children's Hospital of Philadelphia
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group TitleBone Marrow Failure SyndromeImmunodeficiency / Dysregulation
Arm/Group DescriptionReduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Period Title: Overall Study
STARTED02
COMPLETED02
NOT COMPLETED00

Baseline Characteristics

Arm/Group TitleBone Marrow Failure SyndromeImmunodeficiency / DysregulationTotal
Arm/Group DescriptionReduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.Total of all reporting groups
Overall Participants022
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
9.5
9.5
Sex: Female, Male (Count of Participants)
Female
1
Infinity
1
50%
Male
1
Infinity
1
50%

Outcome Measures

1. Primary Outcome
TitleNumber of Participants With Engraftment
DescriptionThe primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.
Time FrameOne Year

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleBone Marrow Failure SyndromeImmunodeficiency / Dysregulation
Arm/Group DescriptionReduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Measure Participants02
Count of Participants [Participants]
2
Infinity

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group TitleBone Marrow Failure SyndromeImmunodeficiency / Dysregulation
Arm/Group DescriptionReduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
All Cause Mortality
Bone Marrow Failure SyndromeImmunodeficiency / Dysregulation
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/0 (NaN) 0/2 (0%)
Serious Adverse Events
Bone Marrow Failure SyndromeImmunodeficiency / Dysregulation
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/0 (NaN) 0/2 (0%)
Other (Not Including Serious) Adverse Events
Bone Marrow Failure SyndromeImmunodeficiency / Dysregulation
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/0 (NaN) 0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleNancy Bunin, MD
OrganizationChildren's Hospital of Philadelphia
Phone215-590-2255
Emailbuninn@email.chop.edu
Responsible Party:
Nancy Bunin, BMT Medical Director, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT02277639
Other Study ID Numbers:
  • 11-008330
  • CHP 980
First Posted:
Oct 29, 2014
Last Update Posted:
Apr 11, 2018
Last Verified:
Mar 1, 2018