Peripheral Blood Stem Cell Collection for Sickle Cell Disease (SCD) Patients

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT03226691
• Collaborator: St. Jude Children's Research Hospital (Other)
• Enrollment: 15
• Location: 1
• Arm: 1
• Actual Duration (Months): 19.1
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The constitution of blood relies upon hematopoietic stem cells (HSCs), which stay in the bone marrow and differentiate to all lineages of peripheral blood cells. HSC transplantation is the only curative option currently available for sickle cell disease (SCD) patients either via allogeneic HSC transplantation or HSC-targeted gene therapy. Granulocyte-colony stimulating factor (G-CSF)- mobilized HSCs are frequently utilized in the adult setting of HSC transplantation because of the faster hematologic recovery as compared to bone marrow. As an autologous HSC source for gene therapy, bone marrow harvest has been generally employed since G-CSF has been prohibitive in SCD patients due to granulocyte stimulation and the associated reports of vaso-occlusive crises, multi-organ failure, and death. However, when bone marrow harvest is used, the amounts of collected cells are limited and anesthesia is required. In order to obtain HSCs in large numbers without anesthesia, patients will undergo mobilization followed by large volume apheresis. Plerixafor is an alternative treatment for mobilization without direct stimulation to granulocytes, and it is theoretically applicable for SCD patients. The primary endpoint of this study is to obtain sufficient amounts of HSCs collected from the peripheral blood in SCD patients after plerixafor

mobilization with an acceptable safety profile. The harvested products will be stored as backup for patients undergoing gene therapy as well as allogeneic HSC transplantation.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: Plerixafor	Phase 1

Detailed Description

The constitution of blood relies upon hematopoietic stem cells (HSCs), which stay in the bone marrow and differentiate to all lineages of peripheral blood cells. HSC transplantation is the only curative option currently available for sickle cell disease (SCD) patients either via allogeneic HSC transplantation or HSC-targeted gene therapy. Granulocyte-colony stimulating factor (G-CSF)- mobilized HSCs are frequently utilized in the adult setting of HSC transplantation because of the faster hematologic recovery as compared to bone marrow. As an autologous HSC source for gene therapy, bone marrow harvest has been generally employed since G-CSF has been prohibitive in SCD patients due to granulocyte stimulation and the associated reports of vaso-occlusive crises, multi-organ failure, and death. However, when bone marrow harvest is used, the amounts of collected cells are limited and anesthesia is required. In order to obtain HSCs in large numbers without anesthesia, patients will undergo mobilization followed by large volume apheresis. Plerixafor is an alternative treatment for mobilization without direct stimulation to granulocytes, and it is theoretically applicable for SCD patients. The primary endpoint of this study is to obtain sufficient amounts of HSCs collected from the peripheral blood in SCD patients after plerixafor mobilization with an acceptable safety profile. The harvested products will be stored as backup for patients undergoing gene therapy as well as allogeneic HSC transplantation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Peripheral Blood Stem Cell Collection for Sickle Cell Disease (SCD) Patients Using Plerixafor
• Actual Study Start Date: Jul 25, 2017
• Actual Primary Completion Date: Feb 27, 2019
• Actual Study Completion Date: Feb 27, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Cohort - Plerixafor Plerixafor at a single dose of 240 microgram/kg	Drug: Plerixafor; Single-dose subcutaneous administration of plerixafor (Mozobil®) at 240 μg/kg; Other Names: Mozobil®

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Sufficient Collection of Hemopoietic Stem Cells (HSCs) Without Serious Adverse Events [1 day]

   Sufficient collection of HSCs (target 2.0x106 CD34+ cells/kg) from the PB after plerixafor mobilization without serious adverse events (SAEs)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

• SCD patients who are 18 or older, and (a) planned to enroll in an active allogeneic HSCT study where back-up autologous HSCs are needed; OR (b) are eligible for an allogeneic HSCT study (i.e. have the same disease severity as group (a), but no active allogeneic HSCT study is available), and are willing to donate autologous HSCs for a future gene therapy, gene editing, or allogeneic HSCT study.

• Adequate renal function: serum/plasma creatinine <1.5 mg/dL.

• Adequate liver function: direct bilirubin and ALT <5 times the upper limit of normal range.

• Blood counts: WBC >3,000/mm^{3, granulocytes >1,000/mm}3, hemoglobin>7.0g/dL, platelets>150,000/mm^3.

• Female patients of childbearing age should have a negative serum pregnancy test within one week of beginning plerixafor administration, have had a hysterectomy, post-menopausal, or absence of a menses for over a year.

• Meets NIH Department of Transfusion Medicine (DTM) eligibility criteria for blood component donation for in vitro research use (negative serologic tests for syphilis, hepatitis B and C, HIV, and HTLV-1).

• Ability to give informed consent to participate in the protocol.

• Female and male individuals of reproductive potential must agree to one of the contraceptive regimens stated above if sexually active

EXCLUSION CRITERIA:

• Pregnancy. Female patients of childbearing age should have a negative serum pregnancy test within one week of beginning plerixafor administration, except those that have had a hysterectomy, post-menopausal, or an absence of a menses for over a year.

• Active viral, bacterial, fungal, or parasitic infection.

• History of cancer, excluding squamous carcinoma of the skin and cervical carcinoma in situ.

• Active and painful splenomegaly or splenomegaly (size greater than upper limit of normal) determined by ultrasound.

• Allergy to plerixafor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• St. Jude Children's Research Hospital

Investigators

• Principal Investigator: John F Tisdale, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 24, 2020

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT03226691
• Other Study ID Numbers: 170124; 17-H-0124
• First Posted: Jul 24, 2017
• Last Update Posted: Apr 20, 2020
• Last Verified: Jun 6, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by National Heart, Lung, and Blood Institute (NHLBI): Plerixafor; Leukapheresis; Mobilization; Stem Cells; Sickle Cell Disease
• Additional relevant MeSH terms: Anemia, Sickle Cell; Plerixafor

Study Results

Participant Flow

Arm/Group Title	Experimental: Plerixafor
Arm/Group Description	Plerixafor at a single dose of 240 microgram/kg
Period Title: Overall Study
STARTED	15
COMPLETED	15
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Experimental: Plerixafor
Arm/Group Description	Plerixafor at a single dose of 240 microgram/kg
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	8 53.3%
Male	7 46.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	15 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	15 100%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Sufficient Collection of Hemopoietic Stem Cells (HSCs) Without Serious Adverse Events
Description	Sufficient collection of HSCs (target 2.0x106 CD34+ cells/kg) from the PB after plerixafor mobilization without serious adverse events (SAEs)
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

Individuals with SCD age 18 or greater and are willing to donate HSC collection for future gene therapy or gene editing study, if no allogeneic HSC transplantation study was currently available

Arm/Group Title	Experimental: Plerixafor
Arm/Group Description	Plerixafor at a single dose of 240 microgram/kg
Measure Participants	15
Count of Participants [Participants]	14 93.3%

Adverse Events

Time Frame	10 days
Arm/Group Title	Experimental: Plerixafor
Arm/Group Description	Plerixafor at a single dose of 240 microgram/kg
All Cause Mortality
	Experimental: Plerixafor
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Serious Adverse Events
	Experimental: Plerixafor
	Affected / at Risk (%)	# Events
Total	3/15 (20%)
Blood and lymphatic system disorders
Hemolysis	1/15 (6.7%)
General disorders
Pain	2/15 (13.3%)
Other (Not Including Serious) Adverse Events
	Experimental: Plerixafor
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Blood and lymphatic system disorders
Anemia	1/15 (6.7%)
Cardiac disorders
Cardiac disorders - Other specify: irregular heart rate	1/15 (6.7%)
Ear and labyrinth disorders
Tinnitus	1/15 (6.7%)
Eye disorders
Blurred vision	1/15 (6.7%)
Eye disorders - Other specify: double vision	1/15 (6.7%)
Gastrointestinal disorders
Abdominal pain	2/15 (13.3%)
Bloating	2/15 (13.3%)
Constipation	1/15 (6.7%)
Dyspepsia	1/15 (6.7%)
Nausea	2/15 (13.3%)
Vomiting	1/15 (6.7%)
General disorders
Edema face	1/15 (6.7%)
Edema limbs	1/15 (6.7%)
Fatigue	4/15 (26.7%)
Fever	1/15 (6.7%)
General disorders and administration site conditions - Other specify: Leg pain	1/15 (6.7%)
General disorders and administration site conditions - Other specify: Pain	1/15 (6.7%)
Pain at the subcutaneous port site	1/15 (6.7%)
Injection site reaction	2/15 (13.3%)
Non-cardiac chest pain	1/15 (6.7%)
Pain	6/15 (40%)
Injury, poisoning and procedural complications
Postoperative hemorrhage	1/15 (6.7%)
Investigations
Activated partial thromboplastin time prolonged	1/15 (6.7%)
Blood bilirubin increased	1/15 (6.7%)
Platelet count decreased	2/15 (13.3%)
Metabolism and nutrition disorders
Anorexia	1/15 (6.7%)
Hyperglycemia	1/15 (6.7%)
Hypocalcemia	4/15 (26.7%)
Hypokalemia	3/15 (20%)
Hypomagnesemia	6/15 (40%)
Hyponatremia	2/15 (13.3%)
Hypophosphatemia	1/15 (6.7%)
Musculoskeletal and connective tissue disorders
Bone pain	1/15 (6.7%)
Myalgia	1/15 (6.7%)
Nervous system disorders
Brachial plexopathy	1/15 (6.7%)
Headache	6/15 (40%)
Paresthesia	6/15 (40%)
Spasticity	1/15 (6.7%)
Psychiatric disorders
Anxiety	1/15 (6.7%)
Confusion	1/15 (6.7%)
Insomnia	2/15 (13.3%)
Renal and urinary disorders
Acute kidney injury	1/15 (6.7%)
Cystitis noninfective	1/15 (6.7%)
Hematuria	1/15 (6.7%)
Urinary retention	1/15 (6.7%)
Reproductive system and breast disorders
Vaginal dryness	1/15 (6.7%)
Skin and subcutaneous tissue disorders
Pruritus	1/15 (6.7%)
Swelling soft tissue left hand, dorsal interspace between thumb and index finger	1/15 (6.7%)
Vascular disorders
Flushing	1/15 (6.7%)
Hypotension	1/15 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.