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Trial record 1 of 1 for:    NCT03173937 | Recruiting Studies
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Unrelated Umbilical Cord Blood Transplantation for Severe Aplastic Anemia and Hypo-plastic MDS Using CordIn(TM), Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells to Expedite Engraftment and Improve Transplant Outcome

This study is currently recruiting participants.
Verified July 31, 2017 by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
Sponsor:
ClinicalTrials.gov Identifier:
NCT03173937
First Posted: June 2, 2017
Last Update Posted: August 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
  Purpose

Background:

Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are bone marrow diseases. People with these diseases usually need a bone marrow transplant. Researchers are testing ways to make stem cell transplant safer and more effective.

Objective:

To test if treating people with SAA or MDS with a co-infusion of blood stem cells from a family member and cord blood stem cells from an unrelated donor is safe and effective.

Eligibility:

Recipients ages 4-55 with SAA or MDS

Donors ages 4-75

Design:

Recipients will be screened with:

  • Blood, lung, and heart tests
  • Bone marrow biopsy
  • CT scan

Recipients will have an IV line placed into a vein in the neck. Starting 11 days before the transplant they will have several chemotherapy infusions and 1 30-minute radiation dose.

Recipients will get the donor cells through the IV line. They will stay in the hospital 3-4 weeks. After discharge, they will have visits:

  • First 3-4 months: 1-2 times weekly
  • Then every 6 months for 5 years<TAB>

Donors will be screened with:

  • Physical exam
  • Medical history
  • Blood tests

Donors veins will be checked for suitability for stem cell collection. They may need an IV line to be placed in a thigh vein.

Donors will get filgrastim injections daily for 5-7 days. On the last day, they will have apheresis: Blood drawn from one arm or leg runs through a machine and into the other arm or leg. This may be repeated 2 days or 2-4 weeks later.


Condition Intervention Phase
Severe Aplastic Anemia Hypo-Plastic MDS Myelodysplastic Syndrome (MDS) Biological: CordIn(TM) Phase 1 Phase 2

National Heart, Lung, and Blood Institute (NHLBI) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Unrelated Umbilical Cord Blood Transplantation for Severe Aplastic Anemia and Hypo-plastic MDS Using CordIn(TM), Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells to Expedite Engraftment and Improve Transplant Outcome

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):

Primary Outcome Measures:
  • Cord engraftment [ Time Frame: At or before day 100 ]

Secondary Outcome Measures:
  • Treatment related mortality (TRM), and standard transplant outcome variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD, and relapse of disease [ Time Frame: 100 day and 200 day ]

Estimated Enrollment: 62
Actual Study Start Date: June 13, 2017
Estimated Study Completion Date: April 30, 2021
Estimated Primary Completion Date: April 29, 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
CordIn(TM) is a cryopreserved stem/progenitor cell-based product of purified CD133+ cells composed of ex vivo expanded allogeneic UCB cells.
Biological: CordIn(TM)
Stem/progenitor cell-based product of purified CD133+ cells composed of ex vivo expanded allogeneic umbilical/unrelated cord blood (UCB) cells. CordIn(TM) comprises: 1) cord blood-derived ex vivo expanded CD133+ cells (CordIn(TM) cultured fraction (CF)); and 2) the non-cultured cell fraction (CD133-) of the same CBU (CordIn(TM) Noncultured Fraction (NF)). Both fractions, i.e. CordIn(TM) CF and CordIn(TM) NF are kept frozen until they are infused on the day of transplantation.

Detailed Description:

Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are life-threatening bone marrow disorders. For SAA patients, long term survival can be achieved with immunosuppressive treatment. However, of those patients treated with immunosuppressive therapy, one quarter to one third will not respond, and about 50% of responders will relapse.

Combined haplo-cord transplant as an alternative to cord or haploidentical donor alone transplantation has recently been shown to be a viable transplant option for SAA patients lacking an HLA matched donor. In our ongoing protocol 08-H-0046, we have utilized this approach in 25 patients with SAA with 23/25 patients having sustained engraftment and long-term disease free/transfusion free survival. However, engraftment patterns have varied substantially and in some patients, cord engraftment was profoundly delayed or never occurred. A number of strategies to expand hematopoietic progenitor cells (HPC) in vitro to improve engraftment and prevent graft rejection have recently been studied. Nicotimanide (NAM) expanded umbilical cord blood/unrelated cord blood (UCB) can be successfully engrafted in NOD/SCID mice (1) and humans (2) where they appear to have long-term repopulating potential. CordIn(TM) is a cryopreserved stem/progenitor cell-based product of purified CD133+ cells composed of ex vivo expanded allogeneic UCB cells. CordIn(TM) comprises: 1) cord blood-derived ex vivo expanded CD133+ cells (CordIn(TM) cultured fraction (CF)); and 2) the non-cultured cell fraction (CD133-) of the same CBU (CordIn(TM) Non-cultured Fraction (NF)). Both fractions, i.e. CordIn(TM) CF and CordIn(TM) NF are kept frozen until they are infused on the day of transplantation.

This research protocol is therefore designed to evaluate the safety and effectiveness of transplantation with ex vivo expanded UCB (CordIn(TM)) to overcome the high incidence of graft rejection associated with conventional UCB for aplastic anemia, where graft rejection occurs in up to 50% of subjects. We believe, based on preliminary data, that transplantation of CordIn(TM) will not only lead to rapid engraftment, but will also lead to sustained hematopoiesis, expedited immune recovery, and will reduce the chance of cord graft failure in this setting, potentially obviating the need for co-transplanting haploidentical CD34+ cells as a stem cell back-up. This phase II study is designed to have two cohorts: cohort 1 is intended to establish (in as safe a manner as possible) preliminary pilot data to support the capacity for the CordIn unit to engraft in patients with SAA in the presence of haplo CD34+ cells. For cohort 1, three to six subjects will be conditioned then will be transplanted with the thawed CordIn(TM) unit (consisting of the cultured fraction and the non-cultured fraction of the same CBU) and approximately 3 x 106 CD34+ cells/kg from a haploidentical donor which will serve as a backup stem cell source should cord graft failure occur. If 3 of the first 3 to 4 subjects or 4 of 6 subjects achieve early and sustained engraftment (defined as ANC >500 cells/ul by day 26 and a calculated cord ANC >500 cells /ul by day 42 sustained at day 100), the study will move to cohort 2 where up to 23 subsequent subjects will be transplanted with the CordIn(TM) unit alone. For cohort 2, haplo-identical cells will still be collected and cryopreserved as a back-up stem cell source but will not be infused unless there is evidence for failing cord blood engraftment (defined as an ANC < 100 by day 18 or ANC <500 by day 26). In this scenario, the cryopreserved haploidentical donor cells will be thawed and infused to abort impending cord blood engraftment failure.

The primary objective of the Phase II study is to evaluate the ability of the CordIn(TM) unit to achieve sustained early engraftment. Secondary endpoints will include 100 day and 200 day treatment related mortality (TRM), and standard transplant outcome variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD, and relapse of disease. Health related quality of life will also be assessed as secondary outcome measure.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   4 Years to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

-INCLUSION CRITERIA - RECIPIENT:

  1. Diagnosed with severe aplastic anemia characterized by all of the following:

    • Bone marrow cellularity <30% (excluding lymphocytes)
    • Transfusion dependence for platelets and/or RBCs
    • Neutropenia [(absolute neutrophil count < 500 cells/ uL) OR for patients receiving granulocyte transfusions, absolute neutrophil count < 500 cells/ uL before beginning granulocyte transfusions]. OR History of severe aplastic anemia transformed to MDS that meet the following criteria: a) International Prognostic Scoring System (IPSS) risk category of INT-1 or greater, b) < 5% myeloblasts and < 30% of cellularity in the bone marrow on screening morphologic analysis.
  2. Intolerance of or failure to respond to standard immunosuppressive therapy.
  3. Availability of at least one HLA- haploidentical (i.e. greater than or equal to 5/10 and less than or equal to 8/10 HLA match) related donor (HLA-A, B, C, DR, and DQ loci) who is available to donate CD34+ cells (6-75 years old).
  4. Availability of at least one 5/8 HLA-matched (HLA-A, B, C, and DR loci) cord blood unit from the National Marrow Donor Program (NMDP).
  5. The cord blood unit must contain a minimum TNC of at least 1.8 x 10^9 and at least 1.8x10^7/kg TNC and at least 8 x 10^6 CD34+ cells (all doses prior to thawing). The CBU will have undergone volume reduction (both plasma and red blood cell depletion) prior to cryopreservation. All CBUs should be procured from public banks that meet local applicable regulations.
  6. Ages 4-55 years inclusive.
  7. Ability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to subjects aged 4-17 years with formal consent being obtained from parents or legal guardian.

EXCLUSION CRITERIA - RECIPIENT (ANY OF THE FOLLOWING):

  1. Availability of an HLA identical or 9/10 HLA matched (HLA A, B, C, DR, and DQ loci) - relative to serve as a stem cell donor.
  2. The patient is deemed to be a candidate for a 10/10 HLA matched unrelated stem cell transplant (availability of a donor and resources required for such a transplant).
  3. ECOG performance status of 2 or more.
  4. Major anticipated illness or organ failure incompatible with survival from transplant.
  5. Current pregnancy, or unwillingness to take oral contraceptives or use a barrier method of birth control or practice abstinence to refrain from pregnancy, if of childbearing potential for one year.
  6. HIV positive.
  7. Diagnosis of Fanconi s anemia or dyskeratosis congenita.
  8. Diffusion capacity of carbon monoxide (DLCO) <40% predicted (patients under the age of 10 may be excluded from this criterion if they have difficulty performing the test correctly and thus are unable to have their DLCO assessed).
  9. Left ventricular ejection fraction < 40% (evaluated by ECHO) or < 30% (evaluated by MUGA).
  10. Transaminases > 5x upper limit of normal.
  11. Serum bilirubin >4 mg/dl.
  12. Creatinine clearance < 50 cc/min/BSAm^2.
  13. Presence of an active infection not adequately responding to appropriate therapy.
  14. History of a malignant disease liable to relapse or progress within 5 years.
  15. Allergy to bovine, Gentamicin, or to any product which may interfere with the treatment.
  16. Presence of donor-specific antibodies (DSA) to the umbilical cord blood unit and for cohort 1, to the haplo-identical donor.

INCLUSION CRITERIA - RELATED HAPLOIDENTICAL DONOR DONATING PURIFIED CD34+ CELLS:

  1. HLA mismatched family donor ( greater than or equal to 5/10 and less than or equal to 8/10 HLA match (HLA-A, B, C, DR, and DQ loci)) who is available to donate CD34+ cells.
  2. Ages 4-75 inclusive. Note: a pediatric family member will only be considered as a donor if a suitable adult haplo-identical donor is not available.
  3. Weight greater than or equal to 15 kg.
  4. For adults: Ability to comprehend the investigational nature of the study and provide informed consent. For minors: Written informed consent from one parent or guardian who is not the recipient of the transplant and informed assent. The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.
  5. Genetic testing for genes associated with bone marrow failure syndromes (BMFS) perfomed at a CLIA-certified laboratory.

EXCLUSION CRITERIA - RELATED DONOR (ANY OF THE FOLLOWING)

  1. Pregnant or lactating.
  2. A pediatric haplo-identical donor will be excluded if a suitable adult haplo-identical donor is available.
  3. Unfit to receive filgrastim (G-CSF) and undergo apheresis (history of stroke, MI, unstable angina, uncontrolled hypertension, severe heart disease or palpable spleen).
  4. HIV positive (Donors who are positive for HBV, HCV or HTLV-I/II, T.cruzi (Chagas) may be used at the discretion of the investigator following counseling and approval from the recipient).
  Contacts and Locations
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): NCT03173937


Contacts
Contact: Richard W Childs, M.D. (301) 451-7128 childsr@nhlbi.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Richard W Childs, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT03173937     History of Changes
Other Study ID Numbers: 170091
17-H-0091
First Submitted: May 31, 2017
First Posted: June 2, 2017
Last Update Posted: August 7, 2017
Last Verified: July 31, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Haploidentical
Nonmyeloablative

Additional relevant MeSH terms:
Anemia
Myelodysplastic Syndromes
Preleukemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Neoplasms