An Early Phase 1 interventional study of Bortezomib and Busulfan in Beta Thalassemia Major, Sickle Beta 0 Thalassemia and Sickle Beta Plus Thalassemia, sponsored by M.D. Anderson Cancer Center. Withdrawn. Open to participants aged 2 Years to 30 Years. Per ClinicalTrials.gov, last updated 2024-10-24.
Sponsored by M.D. Anderson Cancer Center · Early Phase 1, Interventional, and Treatment
This clinical trial studies the effect of pre-transplant immunosuppression (PTIS) and donor stem cell transplant in treating patients with severe blood diseases (hemoglobinopathies). PTIS helps prepare the body for the transplant and lowers the risk of developing graft versus host disease (GVHD). Hematopoietic cells are found in the bone marrow and produce blood cells. Hematopoietic cell transplantation (HCT) injects healthy hematopoietic cells into the body to support blood cell production. PTIS and HCT may help to control severe hemoglobinopathies.
PRIMARY OBJECTIVE:
I. To estimate event-free survival (EFS) at 2-years post HCT.
SECONDARY OBJECTIVES:
I. Assess event-free survival (EFS) at 100 days and 1 year post HCT. II. Assess overall survival (OS) at 100 days and 1 year post HCT. III. 30-day transplant-related mortality (TRM). IV. Time to platelet and neutrophil engraftment. V. Rate of graft failure (primary and secondary) through day 100. VI. Incidence of acute graft-versus-host disease (aGVHD) by day 100. VII. Incidence of chronic graft-versus-host disease (cGVHD) by 1 year and 2 years.
VIII. Rate of grade II or greater organ toxicity through day 100. IX. Incidence of hepatic sinusoidal obstruction syndrome (SOS) by day 100. X. Incidence of central nervous system (CNS) toxicities including posterior reversible encephalopathy syndrome (PRES) by day 100.
XI. Incidence of infectious complications through day 100.
EXPLORATORY OBJECTIVES:
I. Effect of HCT on clinical and laboratory manifestations of hemoglobinopathies by 1 and 2 years after HCT.
II. Assess the pharmacokinetic profile of busulfan and thymoglobulin to better understand post-transplant outcomes.
III. Assess immune reconstitution kinetics post HCT.
OUTLINE:
DONOR-SPECIFIC ANTI-HLA DESENSITIZATION: Patients with donor-specific anti-HLA antibody titers >= 1:3,000 at the start of PTIS receive rituximab intravenously (IV) on days -69, -41, -28, and -13 and bortezomib IV over less than 1 minute on days -68, -65, -40, and -37 in the absence of unacceptable toxicity. Patients with donor-specific anti-HLA antibody titers > 1:15,000 at the start of PTIS receive receive rituximab IV on days -69, -41, -28, and -13 and bortezomib IV over less than 1 minute on days -68, -65, -62, -58, -40, -37, -34, and -31 in the absence of unacceptable toxicity. Patients with donor-specific anti-HLA antibody titers > 1:5,000 at the start of conditioning may also undergo plasmapheresis on day -12.
PTIS: Patients receive fludarabine phosphate (fludarabine) IV over 1 hour and dexamethasone IV over less than 1 minute on days -68 to -64 and days -40 to -36 in the absence of disease progression or unacceptable toxicity.
CONDITIONING: Patients receive lapine T-lymphocyte immune globulin (rATG) IV over 4-6 hours on days -12 to -10, fludarabine phosphate IV over 1 hour on days -8 to -4, and busulfan IV over 2 hours on days -7 to -4 in the absence of disease progression or unacceptable toxicity.
TRANSPLANT: Patients undergo HCT on day 0.
GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 2-3 hours on days 3 and 4 in the absence of unacceptable toxicity. Beginning on day 5, patients also receive tacrolimus IV continuously daily and then orally (PO) twice daily (BID) at the discretion of the treating physician for up to 12 months, and mycophenolate mofetil IV or PO BID up to day 60 in the absence of unacceptable toxicity.
After completion of HCT, patients are followed up periodically for up to 2 years.
1,103 studies on the registry are indexed under Anemia, Sickle Cell; 235 are open to participants now.
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Patients with SCD should also meet the following eligibility criteria as outlined by the Center for Medicaid and Medicare Services: sickle cell disease and at least one of the following:
Patients with B-thalassemia are considered as severe if they are/have any of the following:
Exclusion Criteria:
Serum conjugated (direct) bilirubin > 2 x upper limit of normal for age. Participants are not excluded if the serum conjugated (direct) bilirubin is > 2 x the upper limit of normal for age as per local laboratory and:
See Detailed Description.
Drug: Bortezomib · Drug: Busulfan · Drug: Cyclophosphamide · Drug: Dexamethasone · Drug: Fludarabine Phosphate · Procedure: Hematopoietic Cell Transplantation · Biological: Lapine T-Lymphocyte Immune Globulin · Drug: Mycophenolate Mofetil · Procedure: Plasmapheresis · Biological: Rituximab · Drug: Tacrolimus
Given IV
Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade
Given IV
Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508
Given IV
Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Given IV
Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex
Given IV
Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586
Undergo HCT
Also known as: HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant, stem cell transplantation
Given IV
Also known as: Anti-Thymocyte Globulin Rabbit, Grafalon, Rabbit Anti-Human Thymocyte Globulin (RATG), Rabbit Anti-Thymocyte Globulin, Rabbit Antithymocyte Globulin, Rabbit ATG, rATG, Thymoglobulin
Given IV or PO
Also known as: CellCept, MMF
Undergo plasmapheresis
Also known as: Plasma Exchange, Therapeutic Plasma Exchange, Therapeutic Plasmapheresis
Given IV
Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima
Given IV or PO
Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic
Event-free survival (EFS)
EFS is defined as survival time following HCT without a qualifying event. Will be summarized by the Kaplan-Meier method with 95% confidence intervals.
Time frame: At 2 years post-hematopoietic cell transplantation (HCT)
Event-free survival
EFS is defined as survival time following HCT without a qualifying event. Will be summarized by the Kaplan-Meier method with 95% confidence intervals.
Time frame: Up to 100 days post-HCT
Event-free survival
EFS is defined as survival time following HCT without a qualifying event. Will be summarized by the Kaplan-Meier method with 95% confidence intervals.
Time frame: Up to 1 year post-HCT
Overall survival
Will be summarized by the Kaplan-Meier method.
Time frame: Up to 100 days post-HCT
Overall survival
Will be summarized by the Kaplan-Meier method.
Time frame: Up to 1 year post-HCT
Transplant-related mortality
Will be summarized by the Kaplan-Meier method.
Time frame: Up to 30 days post-HCT
Time to platelet and neutrophil engraftment
Will be estimated using the method of Gooley et al.
Time frame: Up to 2 years post-HCT
Incidence of graft failure (primary and secondary)
Will be estimated using the method of Gooley et al.
Time frame: Up to 100 days post-HCT
Incidence of acute graft-versus-host disease
Will be estimated using the method of Gooley et al.
Time frame: Up to 100 days post-HCT
Incidence of chronic graft-versus-host disease
Will be estimated using the method of Gooley et al.
Time frame: Up to 1 year post-HCT
Incidence of chronic graft-versus-host disease
Will be estimated using the method of Gooley et al.
Time frame: Up to 2 years post-HCT
Incidence of grade II or greater organ toxicity
Will be reported as counts with percentages.
Time frame: Up to 100 days post-HCT
Incidence of hepatic sinusoidal obstruction syndrome
Will be reported as counts with percentages.
Time frame: Up to 100 days post-HCT
Incidence of central nervous system toxicities including posterior reversible encephalopathy syndrome
Will be reported as counts with percentages.
Time frame: Up to 100 days post-HCT
Incidence of infectious complications
Will be reported as counts with percentages.
Time frame: Up to 100 days post-HCT
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M.D. Anderson Cancer Center