A Phase 1/2 interventional study of Cyclophosphamide 1200 mg/Kg and Fludarabine in SIOD, Cystinosis and FSGS, sponsored by Alice Bertaina. Recruiting at 1 site in United States. Open to participants aged 1 Year to 30 Years. Per ClinicalTrials.gov, last updated 2023-07-17.
Sponsored by Alice Bertaina · Phase 1/2, Interventional, and Treatment
This is a single center, non-randomized, non-controlled open-label phase 1b/2a trial of performing sequential αβdepleted-HSCT and KT in patients requiring KT to prevent kidney rejection post-KT, in the absence of any post-KT immunosuppression, to abrogate the need for lifelong immunosuppression, the risk of chronic rejection and, ultimately, the need for repeated transplantation.
45 studies on the registry are indexed under Cystinosis; 14 are open to participants now.
This study's planned enrollment of 12 is below the median of 30 across 25 interventional studies indexed under Cystinosis.
Browse Cystinosis studies →Alice Bertaina is the lead sponsor of 2 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Anticipated need for kidney transplant due to:
a. Underlying genetic/immunologic disease the following conditions i. SIOD ii. FSGS iii. Cystinosis iv. SLE v. Membranoproliferative glomerulonephritis vi. Renal vasculitis characterized by positivity of the presence of ANCA vii. Other genetic diseases leading to kidney disease requiring KT Or b. Patients who have rejected a previous KT regardless of the underlying disease
Exclusion Criteria:
An initial cohort of 4 patients will be enrolled as part of the initial Phase 1b safety run-in evaluation. Patients will undergo an αβdepleted hematopoietic stem cell transplant (HSCT) after receiving conditioning regimen A (conditioning regimen type is dependent on underlying disease and not part of the experimental goals). In the presence of donor myeloid engraftment, at least 3 months post-HSCT, patients will undergo a living donor kidney transplant (KT) using same donor as HSCT. In the absence of any clinical signs of kidney rejection, pharmacological immunosuppression (used for KT) will be tapered off by Day +90 post-KT.
Drug: Cyclophosphamide 1200 mg/Kg · Drug: Fludarabine · Radiation: Total Body Irradiation · Drug: ATG · Drug: Rituximab · Device: CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System · Procedure: Kidney Transplant
If the intervention is determined to be safe and non-futile, the study will continue to enroll eight more patients under Phase 2a following the same treatment as Phase 1b.
Drug: Cyclophosphamide 1200 mg/Kg · Drug: Fludarabine · Radiation: Total Body Irradiation · Drug: ATG · Drug: Rituximab · Device: CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System · Procedure: Kidney Transplant
An initial cohort of 4 patients will be enrolled as part of the initial Phase 1b safety run-in evaluation. Patients will undergo an αβdepleted hematopoietic stem cell transplant (HSCT) after receiving conditioning regimen B (conditioning regimen type is dependent on underlying disease and not part of the experimental goals). In the presence of donor myeloid engraftment, at least 3 months post-HSCT, patients will undergo a living donor kidney transplant (KT) using same donor as HSCT. In the absence of any clinical signs of kidney rejection, pharmacological immunosuppression (used for KT) will be tapered off by Day +90 post-KT.
Drug: Fludarabine · Drug: Cyclophosphamide 100 mg/Kg · Radiation: Total Body Irradiation · Drug: ATG · Drug: Rituximab · Drug: Melphalan · Device: CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System · Procedure: Kidney Transplant
If the intervention is determined to be safe and non-futile, the study will continue to enroll eight more patients under Phase 2a following the same treatment as Phase 1b.
Drug: Fludarabine · Drug: Cyclophosphamide 100 mg/Kg · Radiation: Total Body Irradiation · Drug: ATG · Drug: Rituximab · Drug: Melphalan · Device: CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System · Procedure: Kidney Transplant
Drug page: Cyclophosphamide
Cyclophosphamide 1200 mg/Kg will be administered as part of the conditioning regimen A prior to HSCT
Fludarabine (starting dose 0.5 mg/Kg and then PK guided to reach an AUC of 18-20) will be administered as part of the conditioning regimen prior to HSCT
Drug page: Cyclophosphamide
Cyclophosphamide 100 mg/Kg will be administered as part of the conditioning regimen B prior to HSCT
Total Body Irradiation 200 cGy will be administered as part of the conditioning regimen prior to HSCT
Also known as: TBI
ATG 7.5 mg/Kg will be administered as part of the conditioning regimen prior to HSCT
Rituximab 200 mg/m2 will be administered within 24 hours of the HSCT
Melphalan 100 mg/m2 will be administered as part of the conditioning regimen prior to HSCT
CliniMACS® TCRαβ-Biotin and CD19 Systems will be used to create the mobilized peripheral blood stem cells (PBSC) from allogeneic donors depleted of TCRαβ+ T cells and CD19+ B cells to be infused into the patient for the HSCT. The target dose for the number of CD34+ HSC infused is \> 10 x 10\^6 cells/Kg recipient weight. The minimum dose is 2 x 10\^6 cells/Kg. There is no upper limit to the dose of CD34+ HSC infused as long as no more than 1 x 10\^5 TCRαβ+ T-cells/Kg are infused. The target dose of TCRαβ+ T cells/Kg is \< 0.50 x 10\^5.
In the presence of donor myeloid engraftment, at least 3 months post-HSCT, with \> 95% donor CD3+ chimerism, in the absence of signs of active aGvHD or cGvHD (moderate or severe), at least 4 weeks off of immunosuppression for any previously occurring acute or chronic GvHD (except single agent treatment of mild cGvHD), and with a BMI \>18.5, ambulatory and active in addition to the eligibility for the standard of care KT criteria, patients will undergo a living donor KT using same donor as HSCT
Number of patients who are able to discontinue immunosuppression post-KT
Donor chimerism equal or greater to 95% after successful HSCT/KT therapy allows for withdrawal of immunosuppressive therapy in patient
Time frame: Day +90 post-KT
Number of patients with successful kidney function
Normal renal function as measured by the glomerular filtration rate (GFR) using the CKiD Under 25 (U25) formula that includes the serum creatinine and the Cystatin C, along with normal protein excretion.
Time frame: +1 year post-KT
Number of patients with myloid engraftment
Cumulative incidence of donor myeloid engraftment by Day +42 post-HSCT. Myeloid engraftment is defined as ANC of \> 0.5 x 109/L for three consecutive laboratory values obtained on different days. Date of myeloid engraftment is the first date of the three lab values taken.
Time frame: Day +42 post-HSCT
Number of patients with persistent full donor chimerism
\>95% donor chimerism for myeloid and lymphoid cells as assessed by peripheral blood (total, CD15+, CD3+, CD19+, CD56+, and CD34+) chimerism by Short Tandem Repeat (STR) or next-generation sequencing (NGS) analysis
Time frame: Day +180 and 1 year post-KT
Number of patients with acute GvHD
Cumulative incidence of acute GvHD (graded as II-IV and III-IV using the Magic criteria)
Time frame: Day +90 and Day +180 post-HSCT
Number of patients with chronic GvHD
Cumulative incidence of chronic GvHD by NIH consensus criteria
Time frame: +1 year post-HSCT
Number of patients with de novo acute GVHD
Cumulative incidence of de novo acute GvHD (graded as II-IV and III-IV using the Magic criteria)
Time frame: +1 year post-KT
Number of patients with de novo chronic GVHD
Cumulative incidence of de novo chronic GVHD as measured by NIH consensus criteria
Time frame: +1 year post-KT
Number of patients with functional tolerance to donor cells
Lack of recipient immune response to donor cells when tested with mixed lymphocyte culture
Time frame: 6- and 12-months post-KT
Number of cases of secondary malignancies
New incidence of secondary malignancies in patients after study participation
Time frame: +5 year post-KT
Plan to share: No
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
No contact was published for this record. The registry link below has the sponsor’s details.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Cyclophosphamide · Melphalan
Alice Bertaina