Hematopoietic Stem Cell Transplant for Sickle Cell Disease

NCT02065596 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CASE12Z13
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study of patients with sickle cell disease. It aims to find out if people with sickle cell disease can be cured by changing their immune system before they have blood stem cell transplants. Doctors will give patients a new drug (fludarabine) to see if this drug changes patients immune system and reduces the patient's cells (host) from rejecting donor cells (graft) after the patient gets a Hematopoietic (blood) stem cell transplant.

Conditions

Sickle Cell Disease; Sickle Cell Anemia; SCD

Keywords

Sickle Cell Disease; Sickle Cell Anemia; GvHD; fludarabine

Outcome Measures

Primary Outcomes (1)

• Probability of Engraftment

  The number of patients with engraftment (as defined as recovery of ANC to 500 cells per cubic mm) compared to the total number of patients treated as a function of the patient's age.

  42 Days after transplant

Secondary Outcomes (12)

• Mean time to engraftment

  42 Days after transplant

• Disease Progression

  1 year

• Overall Survival

  1 year

• Follicular Stimulating Hormone Levels

  1 year

• Luteinizing Hormone Levels

  1 year

Study Arms (1)

Immunomodulation with Fludarabine prior to HSCT

EXPERIMENTAL

Fludarabine given beginning at 25mgm/m2 three times per day. Patients may be escalated up to 25mgm/m2 five times per day depending on dose-limiting toxicity

Drug: Fludarabine; Procedure: Hematopoietic Stem Cell Transplant (HSCT)

Interventions

Fludarabine DRUG

the study will begin with enrollment of an initial safety cohort of at least 10 subjects at the lowest dose, after which enrollment will pause until the dose-limiting toxicity (DLT) period has been completed. If a patient experiences DLT, defined as failure to engraft. In which case, the patient may be advanced to two higher doses.

Also known as: Fludarabine monophosphate

Immunomodulation with Fludarabine prior to HSCT

Hematopoietic Stem Cell Transplant (HSCT) PROCEDURE

Three weeks after Immunomodulation patients will be infused with matched bone marrow from a sibling, unrelated donor, haploidentical donor, or cord blood. Patients will be followed for the following year.

Immunomodulation with Fludarabine prior to HSCT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have one of the following inherited hemoglobin gene disorders:
• a. Hemoglobin SS
• b. Hemoglobin SC
• c. Hemoglobin S-Beta-zero-Thalassemia or
• d. Hemoglobin S-Beta-plus Thalassemia with an episode of multi-organ failure within 5 years of eligibility
• Patients must meet one of the following risk criteria:
• Low Risk (Red Light. Stop and consider therapy closely): Must have matched sibling donor grafts, failed conventional therapy as determined by the PI, and evidence for morbid disease (one of the following):
• a. 2 or more painful episode/year (requiring Emergency Department or inpatient care) x 2 years or
• b. 1 or more diagnoses of Acute Chest Syndrome within 5 years, or
• c. 2-year mortality 5-10% or
• d. Baseline LDH\>600 IU or
• e. History of sepsis, with or without a WBC\>13.5, or
• f. On chronic transfusions
• Moderate Risk (Yellow Light. Reasonable to proceed, but with caution): May have alternate donor grafts (haploidentical or matched unrelated donor), if MSD is not available. Must have history of high-level vasculopathy, as defined by at least one of the criteria below:
• a. Urine Albumin to Creatinine Ratio of \>300mg/g or eGFR 50-90 ml/min x 2 evaluations within 3 months or

You may not qualify if:

• Red cell alloimmunization to a degree that precludes extended transfusion
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Subjects must not have evidence of impaired liver function due to iron overload, +/- hepatitis. Patients will be evaluated by liver consult if ferritin \>1500, history of hepatitis,or ALTis ≥3 X Upper limit of normal (ULN). Recommended evaluations could include liver biopsy if there is evidence for significant hepatic iron deposition or fibrosis/cirrhosis on T2\* MRI of the liver.
• eGFR \<21 ml/min
• ≥2.0 liter-per-minute pm home oxygen requirement
• An estimated Left Ventricular Ejection Fraction ≤40% (echo or MUGA)
• Hepatic cirrhosis (Biopsy Proven)
• HIV positive, ineligible because of the increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• Pregnant or breastfeeding women are excluded from this study because the immunomodulatory treatment, preparative regimen, and anti-GVHD therapy contain agents with the potential for teratogenic or abortifacient effects.
• Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within 1 month prior to starting the conditioning regimen. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen.
• Prior allogeneic marrow or stem cell transplantation.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

fludarabine; fludarabine phosphate; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Molly Gallogly, MD, PhD

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2014
• First Posted: February 19, 2014
• Study Start: October 19, 2015
• Primary Completion: February 17, 2023
• Study Completion: February 17, 2023
• Last Updated: April 29, 2024

Record last verified: 2024-04

Locations

US (1)