Stem Cell Transplant Using Peripheral and Cord Blood Stem Cells to Treat Severe Aplastic Anemia and Myelodysplastic Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00604201
• Date of registration: 08/01/2008
• Prospective Registration: Yes
• Primary sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Public title: Stem Cell Transplant Using Peripheral and Cord Blood Stem Cells to Treat Severe Aplastic Anemia and Myelodysplastic Syndrome
• Scientific title: Co-Infusion of Umbilical Cord Blood and Haploidentical CD34+ Cells Following Nonmyeloablative Conditioning as Treatment for Severe Aplastic Anemia and MDS Associated With Severe Neutropenia Refractory to Immunosuppressive Therapy
• Date of first enrolment: May 21, 2008
• Target sample size: 31
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT00604201
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Richard W Childs, M.D.
• Affiliation: National Heart, Lung, and Blood Institute (NHLBI)

Key inclusion & exclusion criteria

- INCLUSION CRITERIA - RECIPIENT:

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

1. Bone marrow cellularity less than 30 percent (excluding lymphocytes)

2. Transfusion dependence for platelets and/or red blood cells (RBCs)

3. Neutropenia (absolute neutrophil count less than 500 cells/microL) OR for
patients receiving granulocyte transfusions, absolute neutrophil count < 500
cells/microL before beginning granulocyte transfusions].)

OR

- Diagnosed with myelodysplastic syndrome characterized by refractory anemia OR
refractory anemia with ringed sideroblasts (RARS and at least one of the following:

1. Neutropenia [(absolute neutrophil count < 500 cells/microL) OR for patients
receiving granulocyte transfusions, absolute neutrophil count < 500 cells/microL
before beginning granulocyte transfusions]) and history of 1 or more
opportunistic infections related to neutropenia. OR

2. History of severe aplastic anemia transformed to MDS

- Intolerance of or failure to respond standard immunosuppressive therapy.

- 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 DO loci)
who is available to donate CD34+ cells (4-75 years old).

- Availability of at least one 4/6 HLA-matched (HLA-A, B, and DR loci) cord blood unit
from the National Marrow Donor Program (NMDP). The cord blood unit must contain a
minimum total nucleated cells (TNC) (prior to thawing) of at least 1.5 x 10(7) cells
per kilogram of recipient body weight with the following exception: if the minimum
criterion of TNC is not met the cord unit must contain at least 1.7 x 10(5) CD34 plus
cells/kg (prior to thawing).

- Ages 4-55 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.

- Telomere Length Testing

- In patients where a suspicion for a familial bone marrow failure syndromes (BMFS)
exists, TERC and TERT mutation testing will be performed on protocol 04-H-0012 or
performed elsewhere prior to enrolling on 04-H-0012.

EXCLUSION CRITERIA - RECIPIENT:

- Availability of an HLA identical or 9/10 HLA matched(HLA A, B, C, DR, and DO
loci-relative to serve as a stem cell donor.

- The patient is deemed to be a candidate for a 6/6 HLA matched unrelated stem cell
transplant (availability of a donor and resources required for such a transplant).

- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more.

- Major anticipated illness or organ failure incompatible with survival from transplant

- Severe psychiatric illness. Mental deficiency sufficiently severe as to make
compliance with the transplant treatment unlikely and making informed consent
impossible.

- Positive pregnancy test for women of childbearing age.

- HIV positive

- Diagnosis of Fanconi anemia (by chromosome breakage study).

- Diffusion capacity of carbon monoxide (DLCO) less than 40 percent 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) using DL Adj and DL/VA/Adj.

- Left ventricular ejection fraction less than 40 percent (evaluated by ECHO)

- Transaminases greater than 5x upper limit of normal (when transaminases are elevated,
the subject may be excluded at the discretion of the PI).

- Serum bilirubin greater than 4 mg/dl

- Creatinine clearance less than 50 cc/min by 24 hr urine collection (adjusted for body
surface area, i.e.50 ml/min/1.73m(2))

- Serum creatinine > 2.5 mg/dl

- Failure to collect an adequate number of CD34+ cells (i.e. greater than or equal 2 x
10(6) CD34+ cells/kg) for transplantation from the subject s haploidentical relative.

- Presence of an active infection not adequately responding to appropriate therapy

- History of a malignant disease liable to relapse or progress within 5 years

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

- HLA mismatched family donor (greater than or equal to 5/10 and less than or equal to
8/10 HLA matched (HLA-A, B, C, DR and DO loci) who is available to donate CD34+ cells.

- Ages 4-75 inclusive

- Weight greater than or equal to 15 kg.

- 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.

- If there is a suspicion of familial BMFS in the recipient, then the donor must have
undergone genetic testing for genes associated with BMFS - performed at a
CLIA-certified laboratory, prior to enrolling in this protocol.

EXCLUSION CRITERIA RELATED DONOR (ANY OF THE FOLLOWING):

- Pregnant or breastfeeding.

- A suitable adult haplo identical donor is available.

- Unfit to receive filgrastim (G-CSF) and undergo apheresis (history of stroke, MI,
unstable angina, uncontrolled hypertension, severe heart disease or palpable spleen).

- 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).

- Sickling hemoglobinopathies including HbSS, HbAS, HbSC. Donors with HbAS are
acceptable.

- Severe psychiatric illness. Mental deficiency sufficiently severe as to make
compliance with the BMT treatment unlikely and making informed consent impossible.

- Screening test positive for Chagas disease (Trypanosoma cruzi /T.
cruzi/trypanosomiasis) confirmed by the Center for Disease Control (CDC).



Age minimum: 4 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Myelodysplastic Syndrome (MDS) With Refractory Anemia (RA)

Severe Aplastic Anemia (SAA)

Intervention(s)

Biological: Umbilical Cord Blood

Primary Outcome(s)

Number of Participants Who Engrafted by Day 42 [Time Frame: 42 days]

Secondary Outcome(s)

Number of Participants Who Developed Grade II Acute GVHD [Time Frame: 100 days]

Number of Participants Who Developed Steroid Refractory Acute GVHD [Time Frame: 100 days]

Number of Participants Who Developed Moderate Chronic GVHD [Time Frame: 5 years]

Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 200 [Time Frame: 200 days]

Number of Participants Who Developed Acute GVHD [Time Frame: 100 days]

Number of Participants Who Developed Chronic GVHD [Time Frame: 5 years]

Number of Participants Who Developed Mild Chronic GVHD [Time Frame: 5 years]

Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 100 [Time Frame: 100 days]

Number of Participants Who Had ANC Recovery at Day 22 [Time Frame: 22 days]

Number of Participants Who Had Relapse of Disease [Time Frame: 5 years]

Number of Participants Who Developed Grade III Acute GVHD [Time Frame: 100 days]

Number of Participants Who Developed Severe Chronic GVHD [Time Frame: 5 years]

Secondary ID(s)

08-H-0046

080046

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 31/07/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00604201