Pre-transplant Immunosuppression and Donor Stem Cell Transplant for the Treatment of Severe Hemoglobinopathies

NCT04776850 | Withdrawn Early Phase 1 DMC FDA Drug

• 2 other identifiers: 2020-0952NCI-2021-00365
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Beta Thalassemia Major; Sickle Beta 0 Thalassemia; Sickle Beta Plus Thalassemia; Sickle Beta Thalassemia; Sickle Cell Disease; Sickle Cell-SS Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  At 2 years post-hematopoietic cell transplantation (HCT)

Secondary Outcomes (14)

• Event-free survival

  Up to 100 days post-HCT

• Event-free survival

  Up to 1 year post-HCT

• Overall survival

  Up to 100 days post-HCT

• Overall survival

  Up to 1 year post-HCT

• Transplant-related mortality

  Up to 30 days post-HCT

Study Arms (1)

Treatment (PTIS, HCT)

EXPERIMENTAL

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

Interventions

Bortezomib DRUG

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

Treatment (PTIS, HCT)

Busulfan DRUG

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

Treatment (PTIS, HCT)

Cyclophosphamide DRUG

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

Treatment (PTIS, HCT)

Dexamethasone DRUG

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

Treatment (PTIS, HCT)

Fludarabine Phosphate DRUG

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

Treatment (PTIS, HCT)

Hematopoietic Cell Transplantation PROCEDURE

Undergo HCT

Also known as: HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant, stem cell transplantation

Treatment (PTIS, HCT)

Lapine T-Lymphocyte Immune Globulin BIOLOGICAL

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

Treatment (PTIS, HCT)

Mycophenolate Mofetil DRUG

Given IV or PO

Also known as: CellCept, MMF

Treatment (PTIS, HCT)

Plasmapheresis PROCEDURE

Undergo plasmapheresis

Also known as: Plasma Exchange, Therapeutic Plasma Exchange, Therapeutic Plasmapheresis

Treatment (PTIS, HCT)

Rituximab BIOLOGICAL

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

Treatment (PTIS, HCT)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (PTIS, HCT)

Eligibility Criteria

• Age: 2 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients 2-30 years-of-age with confirmed sickle cell disease (SCD) (SS \& sickle beta \[SB\]-thalassemia, both sickle beta 0 \[SB0\] and sickle beta plus \[SB+\]) or severe B-thalassemia major are potentially eligible
• 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:
• Stroke or neurological deficit lasting \> 24 hours
• Recurrent acute chest syndrome (ACS): 2 or more episodes of ACS in 2-year period preceding enrollment
• Recurrent vaso-occlusive pain crises: 3 or more episodes per year in 2-year period preceding enrollment or recurrent priapism (3 or more episodes in the 2 years preceding enrollment)
• Chronic transfusion program defined as 8 or more packed red blood cells (PRBC) transfusions per year to prevent central nervous system and/or vaso-occlusive complications in 1-year period preceding enrollment
• Impaired neuropsychological function and abnormal cerebral magnetic resonance imaging (MRI) scan (silent strokes)
• Stage I or II sickle lung disease
• Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate 30-50% of predicted normal value)
• Bilateral proliferative retinopathy and major visual impairment in at least one eye
• Osteonecrosis of multiple joints
• Echocardiographic finding of tricuspid valve regurgitant jet velocity (TRJV) \>= 2.7 m/sec
• Patients with B-thalassemia are considered as severe if they are/have any of the following:
• Transfusion-dependent
• Evidence of extra-medullary hematopoiesis

You may not qualify if:

• Uncontrolled infection
• Females who are pregnant and/or unwilling to cease breastfeeding
• Seropositivity for human immunodeficiency virus (HIV)
• Lansky or Karnofsky performance status \< 70%
• Life expectancy severely limited by concomitant illness
• Uncontrolled arrhythmias or symptomatic cardiac disease
• Uncontrolled symptomatic pulmonary disease
• Evidence of chronic active hepatitis or cirrhosis
• 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:
• There is evidence of a hyperhemolytic reaction after a recent red blood cell (RBC) transfusion, OR
• There is evidence of moderate direct hyperbilirubinemia defined as direct serum bilirubin \< 5 times upper limit of normal (ULN) and not caused by underlying hepatic disease
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 5 x upper limit of normal for age
• Serum creatinine \> 1.5 x upper limit of normal for age AND estimated or measure creatinine clearance \< 70 mL/min/1.72 m\^2
• Patient, parent or guardian unable/unwilling to provide consent and when indicated, assent
• Patients with available HLA-matched related donor

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

beta-Thalassemia; Anemia, Sickle Cell

Interventions

Bortezomib; Busulfan; Cyclophosphamide; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; fludarabine phosphate; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Antilymphocyte Serum; thymoglobulin; Mycophenolic Acid; Plasmapheresis; Plasma Exchange; Rituximab; CT-P10; Tacrolimus

Condition Hierarchy (Ancestors)

Thalassemia; 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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Blood Transfusion; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Macrolides; Lactones

Study Officials

• Kris M Mahadeo

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: March 2, 2021
• Study Start: December 29, 2020
• Primary Completion: December 5, 2022
• Study Completion: December 5, 2022
• Last Updated: October 24, 2024

Record last verified: 2022-11