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Treatment of Sickle Cell Anemia With Stem Cell Transplant

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ClinicalTrials.gov Identifier: NCT01350232
Recruitment Status : Terminated (Poor accrual)
First Posted : May 9, 2011
Results First Posted : November 20, 2014
Last Update Posted : November 29, 2016
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Sickle Cell Anemia
Sickle Cell-hemoglobin C Disease
Sickle Cell-β0-thalassemia
Interventions Drug: Fludarabine
Drug: Cytarabine
Device: Cellular Infusions
Radiation: Total Body Irradiation
Drug: Cyclophosphamide
Drug: Bortezomib
Drug: Rituximab
Procedure: Plasmapheresis
Enrollment 2
Recruitment Details  
Pre-assignment Details  
Arm/Group Title HSCT
Hide Arm/Group Description

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

Period Title: Overall Study
Started 2
Completed 2
Not Completed 0
Arm/Group Title HSCT
Hide Arm/Group Description

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 Number of Baseline Participants 2
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2 participants
32.3  (3.5)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
<=18 years
0
   0.0%
Between 18 and 65 years
2
 100.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
Female
2
 100.0%
Male
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
  50.0%
White
1
  50.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
1
  50.0%
Unknown or Not Reported
1
  50.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 2 participants
2
1.Primary Outcome
Title Stable Engraftment
Hide Description 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.
Time Frame 180 days post-infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HSCT
Hide Arm/Group Description:

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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Organ Toxicity
Hide Description To assess organ toxicity related to fludarabine, cytarabine, cyclophosphamide and low-dose total body irradiation in a population with severe sickle cell anemia.
Time Frame 30 days post infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HSCT
Hide Arm/Group Description:

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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Overall Survival
Hide Description 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.
Time Frame 6 months post infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HSCT
Hide Arm/Group Description:

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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Acute Graft Versus Host Disease
Hide Description 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.
Time Frame 100 days post infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HSCT
Hide Arm/Group Description:

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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Correction of Hemoglobinopathy
Hide Description To evaluate the extent of correction of hemoglobinopathy following this reduced intensity transplant.
Time Frame 100 days post infusion through 5 years post infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HSCT
Hide Arm/Group Description:

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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Immune Recovery
Hide Description To assess the pace of lymphoid recovery and associated risk for opportunistic infections and relapse (return to recipient erythropoiesis) in this patient population.
Time Frame 100 days post infusion through 5 years post infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HSCT
Hide Arm/Group Description:

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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Quality of Life
Hide Description To describe the quality of life and functional status following transplantation.
Time Frame Through 5 years post infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HSCT
Hide Arm/Group Description:

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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Cytokine Profile
Hide Description To characterize the profiles of cytokines released following administration of the lymphoid portion of the transplant (donor lymphocyte infusion [DLI]).
Time Frame Through 5 years after infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HSCT
Hide Arm/Group Description:

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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title HSCT
Hide Arm/Group Description

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

All-Cause Mortality
HSCT
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
HSCT
Affected / at Risk (%) # Events
Total   1/2 (50.00%)    
General disorders   
Chest pain  1/2 (50.00%)  1
Knee pain  1/2 (50.00%)  1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
HSCT
Affected / at Risk (%) # Events
Total   2/2 (100.00%)    
Blood and lymphatic system disorders   
Hyperbilirubinemia  1/2 (50.00%)  1
Gastrointestinal disorders   
Constipation  2/2 (100.00%)  4
Vomiting  1/2 (50.00%)  1
General disorders   
Abdominal cramps  1/2 (50.00%)  1
Abdominal pain  1/2 (50.00%)  1
Back pain  1/2 (50.00%)  1
Bone pain  1/2 (50.00%)  1
Fever  1/2 (50.00%)  2
Leg pain  1/2 (50.00%)  1
Lethargy  1/2 (50.00%)  1
Malaise  1/2 (50.00%)  1
Migraine  1/2 (50.00%)  1
Nausea  1/2 (50.00%)  1
Tingling in fingers/toes  1/2 (50.00%)  1
Hepatobiliary disorders   
Elevated liver enzymes  1/2 (50.00%)  1
Immune system disorders   
CMV reactivation  1/2 (50.00%)  1
Reproductive system and breast disorders   
Vaginal hemorrhage  1/2 (50.00%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1/2 (50.00%)  1
Skin and subcutaneous tissue disorders   
Erythema  1/2 (50.00%)  1
Pruritis  1/2 (50.00%)  1
Study was terminated due to poor accrual. No reportable data has been collected.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Joanne Filicko-O'Hara, MD
Organization: Thomas Jefferson University
Phone: 215-955-8874
Responsible Party: Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
ClinicalTrials.gov Identifier: NCT01350232     History of Changes
Other Study ID Numbers: 09F.327
1-RC2HL101496-0 ( Other Grant/Funding Number: National Heart, Lung, and Blood Institute )
First Submitted: May 4, 2011
First Posted: May 9, 2011
Results First Submitted: November 13, 2014
Results First Posted: November 20, 2014
Last Update Posted: November 29, 2016