Trial Title:
A Study of Immune Suppression Treatment for People With Sickle Cell Disease or β-Thalassemia Who Are Going to Receive an Allogeneic Hematopoietic Cell Transplantation (HCT)
NCT ID:
NCT05736419
Condition:
Sickle Cell Disease
Thalassemia, Beta
Thalassemia
Conditions: Official terms:
Anemia, Sickle Cell
Thalassemia
beta-Thalassemia
Mycophenolic Acid
Dexamethasone
Cyclophosphamide
Rituximab
Fludarabine
Bortezomib
Tacrolimus
Thymoglobulin
Conditions: Keywords:
allogeneic hematopoietic cell transplantation
Sickle Cell Disease
Beta Thalassemia
Thalassemia
23-009
Memorial Sloan Kettering Cancer Center
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
PK-guided fludarabine dosing will be used for each of the 2 cycles, using the InsightRx
DoseMeRx platform.
Arm group label:
Participants with Sickle Cell Disease or β-Thalassemia
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Cyclophosphamide will be administered Post-Transplant
Arm group label:
Participants with Sickle Cell Disease or β-Thalassemia
Intervention type:
Drug
Intervention name:
Tacrolimus
Description:
Tacrolimus will be administered beginning on day +5
Arm group label:
Participants with Sickle Cell Disease or β-Thalassemia
Intervention type:
Drug
Intervention name:
Mycophenolate Mofetil
Description:
Mycophenolate mofetil (MMF) will be administered three times daily starting on day +5.
Arm group label:
Participants with Sickle Cell Disease or β-Thalassemia
Intervention type:
Biological
Intervention name:
Rabbit ATG
Description:
The dose and schedule of ATG will be determined according to the nomogram in Appendix A
Arm group label:
Participants with Sickle Cell Disease or β-Thalassemia
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Standard Regimen: Dexamethasone on days -68 to -64 and days -40 to -36.
Arm group label:
Participants with Sickle Cell Disease or β-Thalassemia
Intervention type:
Drug
Intervention name:
Bortezomib
Description:
Bortezomib on days -71, -68, -65, -61, -43, -40, -37, and -33
Arm group label:
Participants with Sickle Cell Disease or β-Thalassemia
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Rituximab on days -71, -58, -43, and -30.
Arm group label:
Participants with Sickle Cell Disease or β-Thalassemia
Summary:
Hematopoietic Cell Transplantation/HCT involves receiving healthy blood-forming cells
(stem cells) from a donor to replace the diseased or damaged cells in participants' bone
marrow. The researchers think giving participants treatment with fludarabine and
dexamethasone, drugs that lower the activity of the body's immune system (immune
suppression), before standard conditioning therapy and HCT may help prevent serious side
effects, including graft failure and GvHD. In this study, depending on how participants'
body responds to the fludarabine and dexamethasone, the study doctor may decide
participants should receive another drug, called cyclophosphamide, instead of
fludarabine. In addition, depending on the results of participants' routine blood tests,
participants may receive the drugs bortezomib and rituximab, which also help with immune
suppression.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age > 12 and < 35 years. Patients of age 2-12 and 35-50 years will be included after
8 patients reach day 100 without TRM and if ≥ 4 of the first 8 patients reach day
100 without graft failure or grade III-IV acute GvHD.
- Suitable haploidentical donor.
- Performance score ≥ 70% by Karnofsky Performance Scale or 0 to 1 by ECOG (age > 16
years), or Lansky Play-Performance Scale ≥ 70% (age ≤ 16 years).
- Adequate major organ system function as demonstrated by:
- For patients ≥ 18 years of age:
- eGFR ≥ 50 mL/min by Cockcroft-Gault formula
- For patients < 18 years of age:
- Serum creatinine clearance: glomerular filtration rate [GFR]) must be >50
mL/min/1.73 m2 as calculated by the Schwartz formula
- Conjugated (direct) bilirubin less than 2x upper limit of normal.
- ALT or AST ≤ 3 times institutional upper limit of normal.
- Left ventricular ejection fraction ≥ 50%.
- Diffusing capacity for carbon monoxide (DLCO) ≥ 50% predicted, corrected for
hemoglobin. For children < 7 years of age who are unable to perform PFT, oxygen
saturation > 92% on room air by pulse oximetry.
- For SCD patients: HbSS, HbSC, HbS/β° with one or more of the following
complications:
- Acute chest syndrome: 2 or more episodes in the 2 years preceding enrollment
- Vaso-occlusive episodes: 3 or more episodes in the 2 years preceding enrollment
- Recurrent priapism: 2 or more episodes in the 2 years preceding enrollment
- History of osteomyelitis or osteonecrosis
- Cerebrovascular disease:
- Imaging evidence of prior overt or silent stroke
- History of a neurologic event resulting in focal neurologic deficits lasting > 24
hours
- Abnormal transcranial Doppler: Timed average maximum mean velocity ≥ 200 cm/sec in
terminal portion of the carotid or proximal portion of the middle cerebral artery or
> 185 cm/sec plus evidence of intracranial vasculopathy if imaging TCD is used
- Pulmonary hypertension: Confirmed by right heart catheterization with mean
pulmonary arterial pressure ≥ 25 mmHg or mean pulmonary vascular resistance > 2
Wood units
- Red blood cell alloimmunization (> 3 alloantibodies)
- For thalassemia patients: Any genotype, with all of the following:
- Onset of red blood cell transfusion dependence during the first 3 years of life
- RBC transfusion history > 225 mL/kg/year or > 15 lifetime RBC transfusions
- Pre-transfusion hemoglobin ≤ 7 g/dL
- Hepatosplenomegaly
- Patient or the patient's legal representative, parent(s) or guardian should be able
to provide written informed consent. Assent of a minor if participant's age is at
least seven and less than eighteen years.
- For sexually active men and women of childbearing potential, must agree to use a
form of contraception considered effective and medically acceptable by the
Investigator.
Exclusion Criteria:
- Prior myeloablative allogeneic HCT.
- Overt stroke or CNS instrumentation (e.g. for Moyamoya disease) within 6 months of
enrollment.
- Liver cirrhosis. Mild fibrosis will be permitted, i.e. fine reticulin or grade 1 of
4, with bridging fibrosis.
- Hepatic iron content ≥ 3 mg Fe/g liver dry weight
- HIV positive
- Active hepatitis B or C.
- Other uncontrolled infections.
- BMI > 40.
- Other malignancy/cancer diagnosis unless in remission after definitive therapy for a
minimum of 2 years. Exceptions: Ductal carcinoma in situ, basal cell carcinoma,
cervical intraepithelial neoplasia.
- Positive pregnancy test in a woman with child-bearing potential, defined as not
post-menopausal for 12 months or no previous surgical sterilization.
- Inability to comply with medical therapy or follow-up.
- Known history of allergic reactions to any constituents of the cell product,
including a known history of allergic reactions to DMSO.
Gender:
All
Minimum age:
2 Years
Maximum age:
50 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering at Basking Ridge (Consent only)
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Maria Cancio, MD
Phone:
212-639-2446
Facility:
Name:
Memorial Sloan Kettering Monmouth (Consent only)
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Maria Cancio, MD
Phone:
212-639-2446
Facility:
Name:
Memorial Sloan Kettering Bergen (Consent only)
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Maria Cancio, MD
Phone:
212-639-2446
Facility:
Name:
Memorial Sloan Kettering Suffolk - Commack (Consent only)
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Maria Cancio, MD
Phone:
212-639-2446
Facility:
Name:
Memorial Sloan Kettering Westchester (Consent only)
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Maria Cancio, MD
Phone:
212-639-2446
Facility:
Name:
Memorial Sloan Kettering Nassau (All protocol activities)
Address:
City:
Rockville Centre
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Maria Cancio, MD
Phone:
212-639-2446
Start date:
February 9, 2023
Completion date:
February 9, 2026
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05736419
http://www.mskcc.org
