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

Launched by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE (NHLBI) · Jun 1, 2017

Keywords

ClinConnect Summary

This clinical trial is exploring a new way to treat severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS), which are serious bone marrow diseases that often require a transplant. The study is testing a method where patients receive a mix of stem cells from both a family member and umbilical cord blood from an unrelated donor. The goal is to see if this approach is safe and can help patients recover better and faster after the transplant.

To be eligible for this trial, participants must be between 4 to 60 years old and diagnosed with SAA or MDS. They will undergo several tests to ensure they are suitable for the procedure, which includes chemotherapy and radiation before receiving the stem cells through an IV. Participants will spend about 3 to 4 weeks in the hospital and will have regular follow-up appointments for up to five years after the transplant. Donors, who must be between 4 to 75 years old, will also go through a screening process and receive medication to help increase their stem cell production before their cells are collected. This trial is currently accepting participants, so if you or someone you know might be interested, it's a good idea to discuss it with a healthcare provider.

Gender

ALL

Eligibility criteria

• * INCLUSION CRITERIA - RECIPIENT:
• • Diagnosed with severe aplastic anemia with bone marrow cellularity \<30% (excluding lymphocytes) associated with RBC or platelet transfusion dependence and/or neutropenia (absolute neutrophil count \<=1000 cells/ uL or for patients receiving granulocyte transfusions, absolute neutrophil count \<=1000 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.
• • -Intolerance of or failure to respond to standard immunosuppressive therapy.
• • Identification of either a) at least one alternative donor (i.e. HLA- haploidentical related donor (i.e. \>=5/10 HLA match: HLA-A, B, C, DR, and DQ loci) or \>=9/10 HLA matched unrelated donor) who is available to serve as a stem cell donor for a salvage allogeneic transplant in the event that the CordIn(TM) unit has been rejected or b) umbilical cord blood unit/s that can be used for a salvage cord blood transplant in the event that the CordIn(TM) unit has been rejected.
• • -Availability of at least one \>=4/8 HLA matched (HLA-A, B, C, and DR loci) cord blood unit from the National Marrow Donor Program (NMDP).
• • The cord blood unit must contain a minimum TNC of at least 1.8 x 10\^9 and at least 1.5x10\^7/kg TNC and at least 8 x 10\^6 CD34+ cells (all doses prior to thawing).
• • Exception: Cord units containing at least 8 x 10\^6 CD34+ cells but less than 1.8 x 10\^9 TNC may be eligible for use on this trial if
• • 1. the pre-expansion CD34/kg recipient cell number is at least 1.5 x 10\^5 /kg
• • AND
• • 2. approval for use of this cord unit for expansion is granted by Gamida Cell.
• • 3. the final cell counts on the cultured and non-cultured fractions meet the IND specified minimal release criteria.
• • 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.
• • Ages 4-60 years inclusive.
• • 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):
• • Availability of an HLA identical (12/12) matched related or unrelated donor who is available within optimal timeline and suitable considering graft source and established donor selection factors (e.g. age, sex, viral exposure, ABO compatibility, pregnancy status, etc) per PI discretion.
• • ECOG performance status of 2 or more.
• • Major anticipated illness or organ failure incompatible with survival from transplant.
• • 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.
• • HIV positive.
• • Diagnosis of Fanconi s anemia (by chromosome breakage study).
• • Diffusion capacity of carbon monoxide (DLCO) \<40% using DLCO corrected for Hgb or lung volumes (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).
• • Left ventricular ejection fraction \< 40% (evaluated by ECHO).
• • Transaminases \> 5x upper limit of normal.
• • Serum bilirubin \>4 mg/dl.
• • Creatinine clearance \< 50 cc/min/BSAm2 by 24-hour urine collection adjusted by body surface area.
• • Serum creatinine \> 2.5 mg/dl
• • Presence of an active infection not adequately responding to appropriate therapy.
• • History of a malignant disease liable to relapse or progress within 5 years.
• • Allergy to bovine, Gentamicin, or to any product which may interfere with the treatment.
• • Presence of donor-specific antibodies (DSA) to the umbilical cord blood unit and for cohort 1, to the haplo-identical donor.