Myelodysplastic Syndrome (MDS) With Refractory Anemia (RA)Phase 2NCT00604201
Stem Cell Transplant Using Peripheral and Cord Blood Stem Cells to Treat Severe Aplastic Anemia and Myelodysplastic Syndrome
A Phase 2 study testing Umbilical Cord Blood in people with Myelodysplastic Syndrome (MDS) With Refractory Anemia (RA) and Severe Aplastic Anemia (SAA), run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will evaluate the safety and effectiveness of treating patients with severe aplastic anemia (SAA) or myelodysplastic syndrome (MDS) with both peripheral blood stem cells from a family member and umbilical cord blood stem cells from an unrelated donor. Read more about this study
- Who is it for?
- Ages 4 to 75 years
- Conditions the study is for
- Myelodysplastic Syndrome (MDS) With Refractory Anemia (RA), Severe Aplastic Anemia (SAA)
- What is being tested?
- Umbilical Cord Blood
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 21 May 2008to 14 Sep 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosed with severe aplastic anemia characterized by all of the following:
- Bone marrow cellularity less than 30 percent (excluding lymphocytes)
- Transfusion dependence for platelets and/or red blood cells (RBCs)
- 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:
Show all 15Show fewer
- 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
- 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.
Who cannot join
- 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.
Show all 30Show fewer
- 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.
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official 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
This study will evaluate the safety and effectiveness of treating patients with severe aplastic anemia (SAA) or myelodysplastic syndrome (MDS) with both peripheral blood stem cells from a family member and umbilical cord blood stem cells from an unrelated donor.
Patients with SAA or MDS for whom other treatments have failed or are not available may be eligible for this study. Candidates may not have a tissue-matched sibling or matched unrelated donor and must have a family member who is a partial tissue type match.
Read more
Participants undergo the following tests and procedures:
- Insertion of a central intravenous (IV) line (plastic tube) into a large vein. The tube is used for giving the donated stem cells and antibiotics and other medicines, for transfusions of red blood cells and platelets, and for collecting blood samples.
- Preparatory chemotherapy (fludarabine, cyclophosphamide and anti-thymocyte globulin) and total body irradiation to suppress immunity and prevent rejection of the donated cells.
- Infusion of the donated stem cells and umbilical cord cells.
- Immune suppression with the drugs tacrolimus, mycophenolate mofetil and prednisone to prevent rejection of the donated cells and to prevent graft-versus-host disease (GVHD), a complication of stem cell transplants in which the donors immune cells destroy the patients healthy tissues.
The average hospital stay after stem cell transplantation is 3 to 4 weeks. Patients return for frequent follow-up visits for the first 2 to 4 months after transplantation. Once the patient returns home, his or her referring physician is asked to send results of any laboratory testing to the NIH researchers at least every 3 months for the first 3 years and annually thereafter. Patient follow-up visits are scheduled at NIH at 1, 2, 3, 4 and 5 years after transplantation to monitor for signs of disease or post-transplantation complications, such as infection or GVHD. After 5 years, participants are offered the opportunity to enroll in NHLBIs long-term evaluation and follow-up care protocol.
Read the 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 percent of responders will relapse.
Allogeneic bone marrow transplantation from either HLA-matched sibling or matched unrelated donor cures about 70 percent of patients with SAA and 30-60 percent of patients with MDS. Unfortunately, most patients with these disorders are not suitable candidates for hematopoietic stem cell transplantation (HSCT) due to advanced age or lack of a histocompatible donor. For such patients, transplantation using unrelated cord blood (UCB) has been shown to be a reasonable alternative transplant strategy. The advantage to UCB transplant is the ease and rapidity of availability, requirement of less than perfect HLA match, and lower rates of graft versus host disease compared to mismatched bone marrow or peripheral blood stem cell transplants. The major disadvantage of UCB transplantation in adults is the limited number of nucleated cells contained within the cord unit resulting in prolonged neutropenia and failure of engraftment which contributes to infection and transplant related mortality (TRM). In order to harness the advantage of UCB availability and to overcome the disadvantage of delayed neutrophil recovery, we propose to test whether co-administration of unrelated umbilical cord blood and a relatively low number of highly purified haploidentical peripheral blood CD34+ cells from a related donor might promote rapid engraftment and reduce TRM secondary to prolonged neutropenia associated with conventional umbilical cord blood transplant (UCBT).
This research protocol is therefore designed to evaluate the safety and effectiveness of co-infusion of unrelated umbilical cord blood and haploidentical CD34 plus cells from a related donor following nonmyeloablative conditioning for neutropenic patients with SAA or MDS with refractory anemia (RA) that has proven to be refractory to medical therapy. Subjects will receive a novel non-myeloablative immunosuppressive conditioning regimen of cyclophosphamide, fludarabine, horse ATG (antithymocyte globulin) and one dose of total body irradiation (200cGy) followed by an infusion of the allografts. The haploidentical stem cell product will be T-cell depleted and enriched for CD34 plus cells using the Miltenyi CliniMacs system. To reduce TRM secondary to prolonged neutropenia associated with conventional UCB transplantation, haploidentical CD34+ stem cells will be co-infused with a single UCB unit (serologically matched at greater than or equal to 4/6 HLA loci).
The primary endpoint is donor engraftment by day 42 (defined as an ANC of greater than 500 from either the haplo donor, the cord, or both combined). Secondary endpoints will include standard transplant outcome variables such as non-hematological toxicities, incidence and severity of acute and chronic GVHD, and relapse of disease. We will also evaluate ANC recovery (ANC greater than 500 cells/microl) at day 22, and 100 day and 200 day treatment related mortality (TRM) of this novel transplant approach. Health related quality of life will also be assessed pre-transplant 30 and 100 days post-transplant, and every 6 months until 5 years post transplant.
- Being tested
- Umbilical Cord Blood
- Keywords
- Nonmyeloablative, Haploidentical, Umbilical Cord Blood, SAA, Severe Aplastic Anemia, Myelodysplastic Syndrome, MDS
- Medical subject headings
- Myelodysplastic Syndromes, Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Umbilical Cord BloodBiological
unrelated umbilical cord blood will be co-infused with haploidentical CD34-selected cells from a related donor for treatment of severe aplastic anemia and myelodysplastic syndrome.
| Study group | Role | What they receive |
|---|---|---|
| Co-infusion of UCB and Haploidentical CD34+ cells | Experimental | Stem cell recipients received co-infusion of unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells from a related donor following non-myeloablative conditioning for neutropenic patients with severe aplastic anemia (SAA) or myelodysplastic syndrome (MDS) with refractory anemia (RA) Receives: Biological: Umbilical Cord Blood |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Engrafted by Day 42
Participants who reached engraftment by day 42 (±3 days) defined as an absolute neutrophil count (ANC) of U> U500 cells/µl
Measured: 42 days
Secondary outcomes (12)
Number of Participants Who Developed Chronic GVHD
Participants who developed chronic graft-versus-host disease (GVHD)
Measured: 5 years
Number of Participants Who Developed Acute GVHD
Participants who had acute graft-versus-host disease (GVHD)
Measured: 100 days
Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 100
Number of participants who experienced treatment related mortality (TRM) by day 100
Measured: 100 days
Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 200
Number of participants who experienced treatment related mortality (TRM) by day 200
Measured: 200 days
Number of Participants Who Had ANC Recovery at Day 22
Number of participants who reached engraftment by day 22 (±3 days) defined as an ANC of U> U500 cells/µl
Measured: 22 days
Number of Participants Who Had Relapse of Disease
Participants who had experienced relapse of disease
Measured: 5 years
Number of Participants Who Developed Grade II Acute GVHD
Participants who developed Grade II Acute GVHD as defined by CIMBTR criteria for Organ Stages of Acute GVHD.
Stage II Acute GVHD: Skin - rash on 25-50 percent body surface area; Liver - Total Bilirubin 3.1-6.0 mg/dL; Lower GI - Diarrhea 1001-1500 mL/day.
Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Measured: 100 days
Number of Participants Who Developed Grade III Acute GVHD
Participants who developed Grade III Acute GVHD as defined by CIMBTR criteria for Organ Stages of Acute GVHD.
Stage III Acute GVHD: Skin - Rash on >50% of body surface; Liver - Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI - Diarrhea > 1500 mL/day
Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Measured: 100 days
Number of Participants Who Developed Mild Chronic GVHD
Participants who developed mild chronic graft vs host disease (GVHD).
Mild chronic GVHD is 2 or fewer organs with no more than score 1 and no lung involvement. Mild disease is associated with a good prognosis whereas severe disease is associated with higher treatment-related mortality and lower survival.
Organs are scored on a 0 to 3 scale from no involvement/no symptoms to severe functional compromise.
Measured: 5 years
Number of Participants Who Developed Moderate Chronic GVHD
Participants who experienced moderate chronic GVHD.
Moderate GVHD is 3 or more organs with score 1, any organ with score 2, or lung with score 1, and usually requires systemic immune-suppressive treatment. Mild disease is associated with a good prognosis whereas severe disease is associated with higher treatment-related mortality and lower survival.
Organs are scored on a 0 to 3 scale from no involvement/no symptoms to severe functional compromise.
Measured: 5 years
Number of Participants Who Developed Severe Chronic GVHD
Participants who developed severe chronic GVHD.
Severe chronic GVHD is any organ with a score of 3 or lung with a score of 2, and means that substantial organ damage already exists. Mild disease is associated with a good prognosis whereas severe disease is associated with higher treatment-related mortality and lower survival
Organs are scored on a 0 to 3 scale from no involvement/no symptoms to severe functional compromise.
Measured: 5 years
Number of Participants Who Developed Steroid Refractory Acute GVHD
Participants who had developed steroid refractory (not responding to standard steroid therapy) acute GVHD.
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2008 (estimated)
- Study start21 May 2008
- Primary completion25 Oct 2016
- Study completion14 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic Syndrome (MDS) With Refractory Anemia (RA)Studies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Richard W Childs, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00604201
- Sponsor's protocol ID
- 080046
- Other IDs
- 08-H-0046
- Status last verified
- Dec 2021
- First submitted
- 8 Jan 2008
- Last updated
- 5 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. No abstract available.
PubMed 7780125Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. doi: 10.1056/NEJM199705083361906. No abstract available.
PubMed 9134878Zoumbos NC, Gascon P, Djeu JY, Trost SR, Young NS. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257-65. doi: 10.1056/NEJM198501313120501.
PubMed 2981406Giudice V, Wu Z, Kajigaya S, Fernandez Ibanez MDP, Rios O, Cheung F, Ito S, Young NS. Circulating S100A8 and S100A9 protein levels in plasma of patients with acquired aplastic anemia and myelodysplastic syndromes. Cytokine. 2019 Jan;113:462-465. doi: 10.1016/j.cyto.2018.06.025. Epub 2018 Jun 27.
PubMed 29958797Giudice V, Banaszak LG, Gutierrez-Rodrigues F, Kajigaya S, Panjwani R, Ibanez MDPF, Rios O, Bleck CK, Stempinski ES, Raffo DQ, Townsley DM, Young NS. Circulating exosomal microRNAs in acquired aplastic anemia and myelodysplastic syndromes. Haematologica. 2018 Jul;103(7):1150-1159. doi: 10.3324/haematol.2017.182824. Epub 2018 Apr 19.
PubMed 29674506
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00604201
- Acronym / sponsor ID
- 080046
- Keywords
- Nonmyeloablative, Haploidentical, Umbilical Cord Blood, SAA, Severe Aplastic Anemia, Myelodysplastic Syndrome, MDS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 21 May 2008 (actual)
- Primary completion
- 25 Oct 2016 (actual)
- Study completion
- 14 Sep 2021 (actual)
- First posted
- 30 Jan 2008 (estimated)
- Results
- Posted 31 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and effectiveness of treating patients with severe aplastic anemia (SAA) or myelodysplastic syndrome (MDS) with both peripheral blood stem cells from a family member and umbilical cord blood stem cells from an unrelated donor.
Patients with SAA or MDS for whom other treatments have failed or are not available may be eligible for this study. Candidates may not have a tissue-matched sibling or matched unrelated donor and must have a family member who is a partial tissue type match.
Participants undergo the following tests and procedures:
- Insertion of a central intravenous (IV) line (plastic tube) into a large vein. The tube is used for giving the donated stem cells and antibiotics and other medicines, for transfusions of red blood cells and platelets, and for collecting blood samples.
- Preparatory chemotherapy (fludarabine, cyclophosphamide and anti-thymocyte globulin) and total body irradiation to suppress immunity and prevent rejection of the donated cells.
- Infusion of the donated stem cells and umbilical cord cells.
- Immune suppression with the drugs tacrolimus, mycophenolate mofetil and prednisone to prevent rejection of the donated cells and to prevent graft-versus-host disease (GVHD), a complication of stem cell transplants in which the donors immune cells destroy the patients healthy tissues.
The average hospital stay after stem cell transplantation is 3 to 4 weeks. Patients return for frequent follow-up visits for the first 2 to 4 months after transplantation. Once the patient returns home, his or her referring physician is asked to send results of any laboratory testing to the NIH researchers at least every 3 months for the first 3 years and annually thereafter. Patient follow-up visits are scheduled at NIH at 1, 2, 3, 4 and 5 years after transplantation to monitor for signs of disease or post-transplantation complications, such as infection or GVHD. After 5 years, participants are offered the opportunity to enroll in NHLBIs long-term evaluation and follow-up care protocol.
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 percent of responders will relapse.
Allogeneic bone marrow transplantation from either HLA-matched sibling or matched unrelated donor cures about 70 percent of patients with SAA and 30-60 percent of patients with MDS. Unfortunately, most patients with these disorders are not suitable candidates for hematopoietic stem cell transplantation (HSCT) due to advanced age or lack of a histocompatible donor. For such patients, transplantation using unrelated cord blood (UCB) has been shown to be a reasonable alternative transplant strategy. The advantage to UCB transplant is the ease and rapidity of availability, requirement of less than perfect HLA match, and lower rates of graft versus host disease compared to mismatched bone marrow or peripheral blood stem cell transplants. The major disadvantage of UCB transplantation in adults is the limited number of nucleated cells contained within the cord unit resulting in prolonged neutropenia and failure of engraftment which contributes to infection and transplant related mortality (TRM). In order to harness the advantage of UCB availability and to overcome the disadvantage of delayed neutrophil recovery, we propose to test whether co-administration of unrelated umbilical cord blood and a relatively low number of highly purified haploidentical peripheral blood CD34+ cells from a related donor might promote rapid engraftment and reduce TRM secondary to prolonged neutropenia associated with conventional umbilical cord blood transplant (UCBT).
This research protocol is therefore designed to evaluate the safety and effectiveness of co-infusion of unrelated umbilical cord blood and haploidentical CD34 plus cells from a related donor following nonmyeloablative conditioning for neutropenic patients with SAA or MDS with refractory anemia (RA) that has proven to be refractory to medical therapy. Subjects will receive a novel non-myeloablative immunosuppressive conditioning regimen of cyclophosphamide, fludarabine, horse ATG (antithymocyte globulin) and one dose of total body irradiation (200cGy) followed by an infusion of the allografts. The haploidentical stem cell product will be T-cell depleted and enriched for CD34 plus cells using the Miltenyi CliniMacs system. To reduce TRM secondary to prolonged neutropenia associated with conventional UCB transplantation, haploidentical CD34+ stem cells will be co-infused with a single UCB unit (serologically matched at greater than or equal to 4/6 HLA loci).
The primary endpoint is donor engraftment by day 42 (defined as an ANC of greater than 500 from either the haplo donor, the cord, or both combined). Secondary endpoints will include standard transplant outcome variables such as non-hematological toxicities, incidence and severity of acute and chronic GVHD, and relapse of disease. We will also evaluate ANC recovery (ANC greater than 500 cells/microl) at day 22, and 100 day and 200 day treatment related mortality (TRM) of this novel transplant approach. Health related quality of life will also be assessed pre-transplant 30 and 100 days post-transplant, and every 6 months until 5 years post transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Co-infusion of UCB and Haploidentical CD34+ cells | Experimental | Biological: Umbilical Cord BloodStem cell recipients received co-infusion of unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells from a related donor following non-myeloablative conditioning for neutropenic patients with severe aplastic anemia (SAA) or myelodysplastic syndrome (MDS) with refractory anemia (RA) |
Who may qualify
- Ages
- 4 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Diagnosed with severe aplastic anemia characterized by all of the following:
- OR
- Diagnosed with myelodysplastic syndrome characterized by refractory anemia OR refractory anemia with ringed sideroblasts (RARS and at least one of the following:
- 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).
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Umbilical Cord Bloodunrelated umbilical cord blood will be co-infused with haploidentical CD34-selected cells from a related donor for treatment of severe aplastic anemia and myelodysplastic syndrome. | Biological | Co-infusion of UCB and Haploidentical CD34+ cells |
Primary outcome
Number of Participants Who Engrafted by Day 42
Time frame: 42 days
Participants who reached engraftment by day 42 (±3 days) defined as an absolute neutrophil count (ANC) of U> U500 cells/µl
12 secondary outcomes
Number of Participants Who Developed Chronic GVHD
Time frame: 5 years
Number of Participants Who Developed Acute GVHD
Time frame: 100 days
Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 100
Time frame: 100 days
Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 200
Time frame: 200 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 II Acute GVHD
Time frame: 100 days
Number of Participants Who Developed Grade III Acute GVHD
Time frame: 100 days
Number of Participants Who Developed Mild Chronic GVHD
Time frame: 5 years
Number of Participants Who Developed Moderate Chronic GVHD
Time frame: 5 years
Number of Participants Who Developed Severe Chronic GVHD
Time frame: 5 years
Number of Participants Who Developed Steroid Refractory Acute GVHD
Time frame: 100 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 7780125Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. No abstract available.
- Background: PubMed 9134878Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. doi: 10.1056/NEJM199705083361906. No abstract available.
- Background: PubMed 2981406Zoumbos NC, Gascon P, Djeu JY, Trost SR, Young NS. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257-65. doi: 10.1056/NEJM198501313120501.
- Derived from this study: PubMed 29958797Giudice V, Wu Z, Kajigaya S, Fernandez Ibanez MDP, Rios O, Cheung F, Ito S, Young NS. Circulating S100A8 and S100A9 protein levels in plasma of patients with acquired aplastic anemia and myelodysplastic syndromes. Cytokine. 2019 Jan;113:462-465. doi: 10.1016/j.cyto.2018.06.025. Epub 2018 Jun 27.
- Derived from this study: PubMed 29674506Giudice V, Banaszak LG, Gutierrez-Rodrigues F, Kajigaya S, Panjwani R, Ibanez MDPF, Rios O, Bleck CK, Stempinski ES, Raffo DQ, Townsley DM, Young NS. Circulating exosomal microRNAs in acquired aplastic anemia and myelodysplastic syndromes. Haematologica. 2018 Jul;103(7):1150-1159. doi: 10.3324/haematol.2017.182824. Epub 2018 Apr 19.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard W Childs, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Umbilical Cord Blood in people with Myelodysplastic Syndrome (MDS) With Refractory Anemia (RA) and Severe Aplastic Anemia (SAA), run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Engrafted by Day 42 (time frame: 42 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00604201, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2022; AzTrials last refreshed its copy on 26 Oct 2026.