Trial Outcomes & Findings for Treatment of Sickle Cell Anemia With Stem Cell Transplant (NCT NCT01350232)

Last Updated: 2025-05-16

Results Overview

To determine if the reduced intensity preparative regimen of fludarabine, cytarabine, cyclophosphamide and low-dose total body irradiation will generate stable engraftment with donor hematopoietic stem cells in at least 80% of patients with severe sickle cell anemia.

Recruitment status

TERMINATED

Study phase

Target enrollment

2 participants

Primary outcome timeframe

180 days post-infusion

Results posted on

2025-05-16

Participant Flow

Participant milestones

Participant milestones
Measure	HSCT Subjects receive the preparative regimen in 2 steps. The "first step" will be with fludarabine and cytarabine and a low dose of total body irradiation. This will be followed by the "first step" of the transplant graft - the donor lymphocytes. The "second step" of the chemotherapy will be two doses of cyclophosphamide. This will then be followed by the "second step" of the transplant graft - the stem cells. Only subjects with prior alloimmunization against donor will receive desensitization. Subjects who demonstrate alloimmunization against the HLA of the donor will receive bortezomib and rituximab in combination with plasmapheresis prior to the admission for transplant. Fludarabine: Subjects will receive fludarabine at a dose of 30 mg/m2 daily for 4 days as part of the preparative regimen Cytarabine: Subjects will receive cytarabine at a dose of 2 g/m2 daily for 4 days, approximately 4 hours after the fludarabine Cellular Infusions: Subjects will receive the cellular
Overall Study STARTED	2
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment of Sickle Cell Anemia With Stem Cell Transplant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HSCT n=2 Participants Subjects receive the preparative regimen in 2 steps. The "first step" will be with fludarabine and cytarabine and a low dose of total body irradiation. This will be followed by the "first step" of the transplant graft - the donor lymphocytes. The "second step" of the chemotherapy will be two doses of cyclophosphamide. This will then be followed by the "second step" of the transplant graft - the stem cells. Only subjects with prior alloimmunization against donor will receive desensitization. Subjects who demonstrate alloimmunization against the HLA of the donor will receive bortezomib and rituximab in combination with plasmapheresis prior to the admission for transplant. Fludarabine: Subjects will receive fludarabine at a dose of 30 mg/m2 daily for 4 days as part of the preparative regimen Cytarabine: Subjects will receive cytarabine at a dose of 2 g/m2 daily for 4 days, approximately 4 hours after the fludarabine Cellular Infusions: Subjects will receive the cellular
Age, Continuous	32.3 years STANDARD_DEVIATION 3.5 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 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	1 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants

PRIMARY outcome

Timeframe: 180 days post-infusion

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 30 days post infusion

To assess organ toxicity related to fludarabine, cytarabine, cyclophosphamide and low-dose total body irradiation in a population with severe sickle cell anemia.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months post infusion

To determine the overall survival at 6 months post-transplant in patients receiving a matched or partially-matched related donor transplant after reduced-intensity conditioning.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 100 days post infusion

To describe the incidence and severity of acute and chronic GVHD following this reduced intensity transplant from partially matched related donors using a combination of cyclophosphamide, tacrolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 100 days post infusion through 5 years post infusion

To evaluate the extent of correction of hemoglobinopathy following this reduced intensity transplant.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 100 days post infusion through 5 years post infusion

To assess the pace of lymphoid recovery and associated risk for opportunistic infections and relapse (return to recipient erythropoiesis) in this patient population.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through 5 years post infusion

To describe the quality of life and functional status following transplantation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through 5 years after infusion

To characterize the profiles of cytokines released following administration of the lymphoid portion of the transplant (donor lymphocyte infusion \[DLI\]).

Outcome measures

Outcome data not reported

Adverse Events

HSCT

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	HSCT n=2 participants at risk Subjects receive the preparative regimen in 2 steps. The "first step" will be with fludarabine and cytarabine and a low dose of total body irradiation. This will be followed by the "first step" of the transplant graft - the donor lymphocytes. The "second step" of the chemotherapy will be two doses of cyclophosphamide. This will then be followed by the "second step" of the transplant graft - the stem cells. Only subjects with prior alloimmunization against donor will receive desensitization. Subjects who demonstrate alloimmunization against the HLA of the donor will receive bortezomib and rituximab in combination with plasmapheresis prior to the admission for transplant. Fludarabine: Subjects will receive fludarabine at a dose of 30 mg/m2 daily for 4 days as part of the preparative regimen Cytarabine: Subjects will receive cytarabine at a dose of 2 g/m2 daily for 4 days, approximately 4 hours after the fludarabine Cellular Infusions: Subjects will receive the cellular
General disorders Chest pain	50.0% 1/2 • Number of events 1
General disorders Knee pain	50.0% 1/2 • Number of events 1

Other adverse events

Other adverse events
Measure	HSCT n=2 participants at risk Subjects receive the preparative regimen in 2 steps. The "first step" will be with fludarabine and cytarabine and a low dose of total body irradiation. This will be followed by the "first step" of the transplant graft - the donor lymphocytes. The "second step" of the chemotherapy will be two doses of cyclophosphamide. This will then be followed by the "second step" of the transplant graft - the stem cells. Only subjects with prior alloimmunization against donor will receive desensitization. Subjects who demonstrate alloimmunization against the HLA of the donor will receive bortezomib and rituximab in combination with plasmapheresis prior to the admission for transplant. Fludarabine: Subjects will receive fludarabine at a dose of 30 mg/m2 daily for 4 days as part of the preparative regimen Cytarabine: Subjects will receive cytarabine at a dose of 2 g/m2 daily for 4 days, approximately 4 hours after the fludarabine Cellular Infusions: Subjects will receive the cellular
General disorders Abdominal cramps	50.0% 1/2 • Number of events 1
General disorders Abdominal pain	50.0% 1/2 • Number of events 1
General disorders Back pain	50.0% 1/2 • Number of events 1
General disorders Bone pain	50.0% 1/2 • Number of events 1
Immune system disorders CMV reactivation	50.0% 1/2 • Number of events 1
Gastrointestinal disorders Constipation	100.0% 2/2 • Number of events 4
Respiratory, thoracic and mediastinal disorders Dyspnea	50.0% 1/2 • Number of events 1
Hepatobiliary disorders Elevated liver enzymes	50.0% 1/2 • Number of events 1
Skin and subcutaneous tissue disorders Erythema	50.0% 1/2 • Number of events 1
General disorders Fever	50.0% 1/2 • Number of events 2
Blood and lymphatic system disorders Hyperbilirubinemia	50.0% 1/2 • Number of events 1
General disorders Leg pain	50.0% 1/2 • Number of events 1
General disorders Lethargy	50.0% 1/2 • Number of events 1
General disorders Malaise	50.0% 1/2 • Number of events 1
General disorders Migraine	50.0% 1/2 • Number of events 1
General disorders Nausea	50.0% 1/2 • Number of events 1
Skin and subcutaneous tissue disorders Pruritis	50.0% 1/2 • Number of events 1
General disorders Tingling in fingers/toes	50.0% 1/2 • Number of events 1
Reproductive system and breast disorders Vaginal hemorrhage	50.0% 1/2 • Number of events 1
Gastrointestinal disorders Vomiting	50.0% 1/2 • Number of events 1

Additional Information

Joanne Filicko-O'Hara, MD

Thomas Jefferson University

Phone: 215-955-8874

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place