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)

ConditionsSickle Cell Disease Thalassemia, Beta Thalassemia

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age2-50

SponsorMemorial Sloan Kettering Cancer Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 2 and ≤ 50 years

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).

eGFR ≥ 50 mL/min by Cockcroft-Gault formula Formula: ((140 - Age) x Weight (kg)) / (72 x Serum Creatinine (mg/dL) Female Adjustment: Multiply result by 0.85

Disqualifiers

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, if applicable

Trial design

Design model

Single group

Treatments tested in this trial

Fludarabine
Drug
PK-guided fludarabine dosing will be used for each of the 2 cycles, using the InsightRx DoseMeRx platform.
Cyclophosphamide
Drug
Cyclophosphamide will be administered Post-Transplant
Tacrolimus
Drug
Tacrolimus will be administered beginning on day +5
Mycophenolate Mofetil
Drug
Mycophenolate mofetil (MMF) will be administered three times daily starting on day +5.
Rabbit ATG
Biological/Vaccine
The dose and schedule of ATG will be determined according to the nomogram in Appendix A
Dexamethasone
Drug
Standard Regimen: Dexamethasone on days -68 to -64 and days -40 to -36.
Bortezomib
Drug
Bortezomib on days -71, -68, -65, -61, -43, -40, -37, and -33
Rituximab
Drug
Rituximab on days -71, -58, -43, and -30.

Treatment groups

24 Participants

are divided into 1 treatment group

Group A: Participants with Sickle Cell Disease or β-ThalassemiaExperimental treatment 8 interventions

Trial outcomes

Primary outcomes

Number of participants with treatment related mortality/TRM or primary graft failure

The primary outcome is to estimate treatment-related mortality (TRM) or primary graft failure at 1 year post-HCT.

Time frame

1 year

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Memorial Sloan Kettering Cancer Center

Lead sponsor

Source ClinicalTrials.gov

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