Trial Outcomes & Findings for Stem Cell Transplant Using Peripheral and Cord Blood Stem Cells to Treat Severe Aplastic Anemia and Myelodysplastic Syndrome (NCT NCT00604201)

NCT ID: NCT00604201

Last Updated: 2022-01-05

Results Overview

Participants who reached engraftment by day 42 (±3 days) defined as an absolute neutrophil count (ANC) of U\> U500 cells/µl

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 31 participants
• Primary outcome timeframe: 42 days
• Results posted on: 2022-01-05

Participant Flow

Participant milestones

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells 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)
Overall Study STARTED	31
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Age, Categorical <=18 years	13 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 42 days

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

Participants who reached engraftment by day 42 (±3 days) defined as an absolute neutrophil count (ANC) of U> U500 cells/µl

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Engrafted by Day 42	30 Participants

SECONDARY outcome

Timeframe: 5 years

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

Participants who developed chronic graft-versus-host disease (GVHD)

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Developed Chronic GVHD	12 Participants

SECONDARY outcome

Timeframe: 100 days

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

Participants who had acute graft-versus-host disease (GVHD)

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Developed Acute GVHD	5 Participants

SECONDARY outcome

Timeframe: 100 days

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

Number of participants who experienced treatment related mortality (TRM) by day 100

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 100	1 Participants

SECONDARY outcome

Timeframe: 200 days

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

Number of participants who experienced treatment related mortality (TRM) by day 200

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 200	1 Participants

SECONDARY outcome

Timeframe: 22 days

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

Number of participants who reached engraftment by day 22 (±3 days) defined as an ANC of U> U500 cells/µl

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Had ANC Recovery at Day 22	30 Participants

SECONDARY outcome

Timeframe: 5 years

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

Participants who had experienced relapse of disease

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Had Relapse of Disease	1 Participants

SECONDARY outcome

Timeframe: 100 days

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

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.

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Developed Grade II Acute GVHD	3 Participants

SECONDARY outcome

Timeframe: 100 days

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

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.

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Developed Grade III Acute GVHD	2 Participants

SECONDARY outcome

Timeframe: 5 years

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

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.

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Developed Mild Chronic GVHD	10 Participants

SECONDARY outcome

Timeframe: 5 years

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

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.

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Developed Moderate Chronic GVHD	2 Participants

SECONDARY outcome

Timeframe: 5 years

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

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.

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Developed Severe Chronic GVHD	0 Participants

SECONDARY outcome

Timeframe: 100 days

Population: All recipients that received unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells

Participants who had developed steroid refractory (not responding to standard steroid therapy) acute GVHD.

Outcome measures

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 Participants 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)
Number of Participants Who Developed Steroid Refractory Acute GVHD	0 Participants

Adverse Events

Co-infusion of UCB and Haploidentical CD34+ Cells

Serious events: 28 serious events

Other events: 0 other events

Deaths: 5 deaths

Serious adverse events

Measure	Co-infusion of UCB and Haploidentical CD34+ Cells n=31 participants at risk 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)
Blood and lymphatic system disorders Epstein-Barr virus associated lymphoproliferative disorder	6.5% 2/31 • Number of events 3 • 5 years
Blood and lymphatic system disorders Febrile neutropenia	19.4% 6/31 • Number of events 7 • 5 years
Blood and lymphatic system disorders Haemolysis	3.2% 1/31 • Number of events 2 • 5 years
Blood and lymphatic system disorders Neutropenia	9.7% 3/31 • Number of events 3 • 5 years
Blood and lymphatic system disorders Pancytopenia	3.2% 1/31 • Number of events 1 • 5 years
Cardiac disorders Cardiac arrest	3.2% 1/31 • Number of events 1 • 5 years
Cardiac disorders Systolic dysfunction	6.5% 2/31 • Number of events 2 • 5 years
Ear and labyrinth disorders Ear infection	3.2% 1/31 • Number of events 1 • 5 years
Endocrine disorders Hyperglycaemia	3.2% 1/31 • Number of events 1 • 5 years
Eye disorders Scleritis	3.2% 1/31 • Number of events 1 • 5 years
Gastrointestinal disorders Abdominal pain	16.1% 5/31 • Number of events 5 • 5 years
Gastrointestinal disorders Acute graft versus host disease in intestine	6.5% 2/31 • Number of events 3 • 5 years
Gastrointestinal disorders Chronic graft versus host disease in intestine	6.5% 2/31 • Number of events 2 • 5 years
Gastrointestinal disorders Clostridium difficile colitis	3.2% 1/31 • Number of events 1 • 5 years
Gastrointestinal disorders Colitis	3.2% 1/31 • Number of events 1 • 5 years
Gastrointestinal disorders Diarrhoea	16.1% 5/31 • Number of events 5 • 5 years
Gastrointestinal disorders Gastrointestinal haemorrhage	3.2% 1/31 • Number of events 1 • 5 years
Gastrointestinal disorders Nausea	9.7% 3/31 • Number of events 3 • 5 years
Gastrointestinal disorders Pancreatitis	3.2% 1/31 • Number of events 3 • 5 years
Gastrointestinal disorders Stomatitis	3.2% 1/31 • Number of events 1 • 5 years
Gastrointestinal disorders Vomiting	9.7% 3/31 • Number of events 3 • 5 years
General disorders Adverse drug reaction	9.7% 3/31 • Number of events 4 • 5 years
Immune system disorders Acute graft versus host disease in intestine	3.2% 1/31 • Number of events 1 • 5 years
Immune system disorders Acute graft versus host disease in liver	3.2% 1/31 • Number of events 1 • 5 years
Immune system disorders Acute graft versus host disease in skin	3.2% 1/31 • Number of events 1 • 5 years
Immune system disorders Chronic graft versus host disease in skin	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Adenovirus infection	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Bacteraemia	9.7% 3/31 • Number of events 4 • 5 years
Infections and infestations Bacterial infection	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations BK virus infection	3.2% 1/31 • Number of events 2 • 5 years
Infections and infestations Capnocytophaga infection	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Infection Reactivation, Cytomegalovirus infection	29.0% 9/31 • Number of events 21 • 5 years
Infections and infestations Encephalitis viral	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Epstein-Barr virus infection	6.5% 2/31 • Number of events 2 • 5 years
Infections and infestations Fungal skin infection	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Herpes simplex	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Herpes virus infection	6.5% 2/31 • Number of events 2 • 5 years
Infections and infestations Infection	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Influenza	9.7% 3/31 • Number of events 4 • 5 years
Infections and infestations Metapneumovirus infection	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Osteomyelitis	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Pneumonia	6.5% 2/31 • Number of events 2 • 5 years
Infections and infestations Pneumonia cytomegaloviral	3.2% 1/31 • Number of events 2 • 5 years
Infections and infestations Pneumonia klebsiella	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Posterior reversible encephalopathy syndrome	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Respiratory syncytial virus infection	9.7% 3/31 • Number of events 3 • 5 years
Infections and infestations Sepsis	6.5% 2/31 • Number of events 2 • 5 years
Infections and infestations Septic shock	6.5% 2/31 • Number of events 2 • 5 years
Infections and infestations Sinusitis	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Staphylococcal infection	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Tonsillitis	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Toxoplasmosis	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Upper respiratory tract infection	6.5% 2/31 • Number of events 2 • 5 years
Infections and infestations Urinary tract infection	3.2% 1/31 • Number of events 1 • 5 years
Infections and infestations Varicella zoster virus infection	6.5% 2/31 • Number of events 2 • 5 years
Infections and infestations Viral infection	9.7% 3/31 • Number of events 3 • 5 years
Investigations Blood culture positive	3.2% 1/31 • Number of events 1 • 5 years
Investigations Body temperature increased	22.6% 7/31 • Number of events 10 • 5 years
Investigations Coronavirus test positive	3.2% 1/31 • Number of events 1 • 5 years
Investigations Stenotrophomonas test positive	3.2% 1/31 • Number of events 1 • 5 years
Investigations Urine electrolytes decreased	3.2% 1/31 • Number of events 1 • 5 years
Musculoskeletal and connective tissue disorders Myotonia	3.2% 1/31 • Number of events 1 • 5 years
Nervous system disorders Posterior reversible encephalopathy syndrome	9.7% 3/31 • Number of events 3 • 5 years
Nervous system disorders Seizure	3.2% 1/31 • Number of events 1 • 5 years
Renal and urinary disorders Acute kidney injury	3.2% 1/31 • Number of events 1 • 5 years
Renal and urinary disorders Chronic kidney disease	3.2% 1/31 • Number of events 1 • 5 years
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	3.2% 1/31 • Number of events 1 • 5 years
Respiratory, thoracic and mediastinal disorders Lung infiltration	3.2% 1/31 • Number of events 1 • 5 years
Respiratory, thoracic and mediastinal disorders Pulmonary alveolar haemorrhage	3.2% 1/31 • Number of events 1 • 5 years
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.2% 1/31 • Number of events 1 • 5 years
Respiratory, thoracic and mediastinal disorders Respiratory distress	3.2% 1/31 • Number of events 1 • 5 years
Skin and subcutaneous tissue disorders Exfoliative rash	3.2% 1/31 • Number of events 1 • 5 years
Skin and subcutaneous tissue disorders Ingrowing nail	3.2% 1/31 • Number of events 1 • 5 years
Surgical and medical procedures Abdominal injury	3.2% 1/31 • Number of events 1 • 5 years
Surgical and medical procedures Dialysis device insertion	3.2% 1/31 • Number of events 1 • 5 years
Vascular disorders Deep vein thrombosis	3.2% 1/31 • Number of events 1 • 5 years
Vascular disorders Hypertension	16.1% 5/31 • Number of events 5 • 5 years
Vascular disorders Hypotension	3.2% 1/31 • Number of events 1 • 5 years
Vascular disorders Venous thrombosis	3.2% 1/31 • Number of events 1 • 5 years

Other adverse events

Adverse event data not reported

Additional Information

Childs, William

National Heart Lung and Blood Institute

Phone: +1 301 451 7128

Email: childsr@nhlbi.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place