RECRUITING

Transplantation of Clustered Regularly Interspaced Short Palindromic Repeats Modified Hematopoietic Progenitor Stem Cells (CRISPR_SCD001) in Patients with Severe Sickle Cell Disease

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is an open label, non-randomized, 2-center, phase 1/2 trial of a single infusion of sickle allele modified cluster of differentiation (CD34+) hematopoietic stem progenitor cells (HSPCs) in subjects with in subjects ≥12 years old to 35 years old severe Sickle Cell Disease (SCD). The study will evaluate the hematopoietic stem cell transplantation (HSCT) using CRISPR/Cas9 edited red blood cells (known as CRISPR_SCD001 Drug Product).

Official Title

Transplantation of CRISPRCas9 Corrected Hematopoietic Stem Cells (CRISPR_SCD001) in Patients with Severe Sickle Cell Disease

Quick Facts

Study Start:2024-09-18

Study Completion:2029-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04774536

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 35 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
1. Male or female 12.00 - 34.99 years of age (at time of consent) who have one or more of the following: 1. History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea); 2. History of at least 4 severe vaso-occlusive pain events in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea); painful episodes related to or any sickle-related acute event are acceptable; a severe painful vaso-occlusive event is defined as receiving analgesic treatment (opioid or other analgesic) for longer than 24 -hours in a hospital or emergency room (ER) observation unit visit or at least 2 visits in a day unit or ER over 72 hours with both visits requiring intravenous analgesics. 2. Participants must have adequate physical function as measured by all of the following: 1. Karnofsky performance score ≥60. 2. Cardiac function: Left ventricular ejection fraction (LVEF) \>40%; or LV shortening fraction \> 26% by cardiac echocardiogram or by (multiple-gated acquisition) MUGA scan. 3. Pulmonary function: Pulse oximetry with a baseline O2 saturation of ≥85% and diffusion capacity of lung for carbon monoxide(DLCO) \> 40% (corrected for hemoglobin). 4. Renal function: Serum creatinine ≤ 1.5 x upper limit of normal for age and estimated or measured creatinine clearance ≥ 70 mL/min/1.73 m2. 5. Hepatic function: 3. Written informed consent or assent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.	1. Participants with uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment (currently taking medication with evidence of progression of clinical symptoms or radiologic findings). 2. Participants with evidence of HIV infection or seropositivity for HIV or active hepatitis B or C. 3. Participants who have received a Hematopoietic Cell Transplant (HCT) 4. Participants who have received a solid organ transplant. 5. Participants who have participated in another clinical trial in which the participant received an investigational or off-label use of a drug or device within 3 months prior to enrollment. 6. Females who are pregnant or breast feeding. 7. Females of child bearing potential (to include all female participants \> 10 years of age, unless postmenopausal for a minimum of 1 year before the time of consent or surgically sterilized) who do not agree to practice two (2) effective methods of contraception at the same time, or who do not agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject, from the time of signing of informed consent through 12 months post-stem cell infusion. 8. Males (even if surgically sterilized) who do not agree to practice effective barrier contraception, or who do not agree to practice true abstinence from the time of signing informed consent through 12 months post-stem cell infusion. 9. Participants who have had a stroke OR who are receiving red blood cell (RBC) transfusions to prevent primary stroke or silent cerebral infarction. 10. Patients who have a human leukocyte antigen identical (HLA-ID) sibling donor 11. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data. 12. Any non-homozygous sickle hemoglobin (HbSS) genotype of SCD

Inclusion Criteria

Exclusion Criteria

1. Male or female 12.00 - 34.99 years of age (at time of consent) who have one or more of the following:
1. History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea);
2. History of at least 4 severe vaso-occlusive pain events in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea); painful episodes related to or any sickle-related acute event are acceptable; a severe painful vaso-occlusive event is defined as receiving analgesic treatment (opioid or other analgesic) for longer than 24 -hours in a hospital or emergency room (ER) observation unit visit or at least 2 visits in a day unit or ER over 72 hours with both visits requiring intravenous analgesics.
2. Participants must have adequate physical function as measured by all of the following:
1. Karnofsky performance score ≥60.
2. Cardiac function: Left ventricular ejection fraction (LVEF) \>40%; or LV shortening fraction \> 26% by cardiac echocardiogram or by (multiple-gated acquisition) MUGA scan.
3. Pulmonary function: Pulse oximetry with a baseline O2 saturation of ≥85% and diffusion capacity of lung for carbon monoxide(DLCO) \> 40% (corrected for hemoglobin).
4. Renal function: Serum creatinine ≤ 1.5 x upper limit of normal for age and estimated or measured creatinine clearance ≥ 70 mL/min/1.73 m2.
5. Hepatic function:
3. Written informed consent or assent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

1. Participants with uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
2. Participants with evidence of HIV infection or seropositivity for HIV or active hepatitis B or C.
3. Participants who have received a Hematopoietic Cell Transplant (HCT)
4. Participants who have received a solid organ transplant.
5. Participants who have participated in another clinical trial in which the participant received an investigational or off-label use of a drug or device within 3 months prior to enrollment.
6. Females who are pregnant or breast feeding.
7. Females of child bearing potential (to include all female participants \> 10 years of age, unless postmenopausal for a minimum of 1 year before the time of consent or surgically sterilized) who do not agree to practice two (2) effective methods of contraception at the same time, or who do not agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject, from the time of signing of informed consent through 12 months post-stem cell infusion.
8. Males (even if surgically sterilized) who do not agree to practice effective barrier contraception, or who do not agree to practice true abstinence from the time of signing informed consent through 12 months post-stem cell infusion.
9. Participants who have had a stroke OR who are receiving red blood cell (RBC) transfusions to prevent primary stroke or silent cerebral infarction.
10. Patients who have a human leukocyte antigen identical (HLA-ID) sibling donor
11. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
12. Any non-homozygous sickle hemoglobin (HbSS) genotype of SCD

Contacts and Locations

Study Contact

Mark Walters, MD

CONTACT

(510) 428-3374

Mark.Walters@ucsf.edu

Christina Chun, MPH

CONTACT

(415) 502-2558

Christina.Chun@ucsf.edu

Principal Investigator

Mark Walters, MD

PRINCIPAL_INVESTIGATOR

UCSF Benioff Children's Hospital Oakland

Study Locations (Sites)

University of California, Los Angeles

Los Angeles, California, 90095

United States

UCSF Benioff Children's Hospital

Oakland, California, 94609

United States

Collaborators and Investigators

Sponsor: Mark Walters, MD

Mark Walters, MD, PRINCIPAL_INVESTIGATOR, UCSF Benioff Children's Hospital Oakland

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-09-18

Study Completion Date2029-03-01

Study Record Updates

Study Start Date2024-09-18

Study Completion Date2029-03-01

Terms related to this study

Additional Relevant MeSH Terms

Sickle Cell Disease