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    DRUG:

    thioguanine

    i
    Other names: 6-TG
    Company:
    Generic mfg.
    Drug class:
    DNA synthesis inhibitor
    Related drugs:
    11d
    Clofarabine or High-Dose Cytarabine and Pegaspargase in Children with ALL (clinicaltrials.gov)
    P2/3, N=745, Completed, Universitätsklinikum Hamburg-Eppendorf | Active, not recruiting --> Completed
    Trial completion
    |
    cytarabine • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • vincristine • daunorubicin • clofarabine • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Amsidine (amsacrine)
    12d
    DIRECTCD: InDuctIon TREatment with SubCuTaneous Infliximab for Crohn's Disease (clinicaltrials.gov)
    P3, N=158, Recruiting, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Trial completion date: Jul 2024 --> Dec 2025 | Trial primary completion date: Jan 2024 --> Jun 2025
    Trial completion date • Trial primary completion date
    |
    mercaptopurine • thioguanine
    1m
    AALL1131: Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations (clinicaltrials.gov)
    P3, N=5949, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025
    Trial completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6)
    |
    MLL rearrangement • MLL rearrangement
    |
    dasatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • methotrexate • vincristine • daunorubicin • clofarabine • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
    1m
    AALL1231: Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma (clinicaltrials.gov)
    P3, N=847, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025
    Trial completion date
    |
    CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • CD22 (CD22 Molecule) • CD34 (CD34 molecule) • CD5 (CD5 Molecule) • CD7 (CD7 Molecule) • CD2 (CD2 Molecule) • MPO (Myeloperoxidase)
    |
    CD22 expression
    |
    cytarabine • bortezomib • doxorubicin hydrochloride • cyclophosphamide • ifosfamide • etoposide IV • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
    2ms
    Large-Scale Pharmacogenomics Analysis of Patients With Cancer Within the 100,000 Genomes Project Combining Whole-Genome Sequencing and Medical Records to Inform Clinical Practice. (PubMed, J Clin Oncol)
    Reporting PGx variants from germline WGS relevant to patients with cancer alongside primary findings related to their cancer can be clinically informative, informing prescribing to reduce the risk of ADRs. Extending the range of actionable variants to those found in patients of non-European ancestry is important and will extend the potential clinical impact.
    Journal
    |
    UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • DPYD (Dihydropyrimidine Dehydrogenase) • NUDT15 (Nudix Hydrolase 15)
    |
    UGT1A1*1*1
    |
    5-fluorouracil • capecitabine • irinotecan • mercaptopurine • thioguanine
    2ms
    A case of rapidly progressive hair loss due to azathioprine, and the prevalence of NUDT15 variants among Japanese patients with autoimmune blistering diseases: A single-center retrospective observational study. (PubMed, J Dermatol)
    Azathioprine is metabolized into thioguanine nucleotides (TGNs) which are its major active metabolites. Our findings indicate a prevalence of NUDT15 variants in AIBD patients that is similar to the prevalences of previous studies on patients with other diseases. These results emphasize the importance of screening for NUDT15 variants prior to initiating azathioprine treatment in Japanese patients with AIBDs.
    Observational data • Retrospective data • Journal
    |
    NUDT15 (Nudix Hydrolase 15)
    |
    thioguanine
    2ms
    Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (clinicaltrials.gov)
    P2, N=171, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2027 --> Dec 2028 | Initiation date: Oct 2024 --> Jan 2025 | Trial primary completion date: Dec 2027 --> Dec 2028
    Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy
    |
    MCL1 (Myeloid cell leukemia 1) • KMT2A (Lysine Methyltransferase 2A) • BCL2L1 (BCL2-like 1)
    |
    BCL2 expression
    |
    Venclexta (venetoclax) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate) • prednisolone
    2ms
    A Study Comparing the Combination of Dasatinib and Chemotherapy Treatment With or Without Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or Philadelphia Chromosome-Like (Ph-Like) ABL-Class B-Cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov)
    P3; Initiation date: Jul 2024 --> Feb 2025
    Trial initiation date
    |
    ABL1 (ABL proto-oncogene 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CD19 (CD19 Molecule) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor)
    |
    CD19 expression
    |
    TruSight RNA Pan-Cancer Panel
    |
    dasatinib • imatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Starasid (cytarabine ocfosfate)
    3ms
    Personalization of thiopurine therapy: Current recommendations and future perspectives. (PubMed, Acta Pharm)
    Despite great therapeutic advances in the field of biologics, small synthetic molecules such as thiopurines, including azathioprine, mercaptopurine, and thioguanine, remain an important therapeutic pillar in the treatment of inflammatory bowel disease, other autoimmune disorders, and cancer. In addition, the article takes a critical look at emerging research in the field of thiopurine pharmaco genomics featuring novel genetic markers and technological developments in genetic testing. Finally, the potential of integrated approaches that combine genetic, meta bolic, and clinical factors to further individualize thiopurine therapy is highlighted.
    Review • Journal
    |
    TPMT (Thiopurine S-Methyltransferase) • NUDT15 (Nudix Hydrolase 15)
    |
    mercaptopurine • thioguanine
    5ms
    Therapy for Newly Diagnosed Patients With B-Cell Precursor Acute Lymphoblastic Leukemia and Lymphoma (clinicaltrials.gov)
    P2, N=128, Not yet recruiting, St. Jude Children's Research Hospital
    New P2 trial
    |
    dasatinib • cytarabine • cyclophosphamide • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • vincristine • daunorubicin • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine
    5ms
    AALL1631: Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P3; Recruiting --> Active, not recruiting
    Combination therapy • Enrollment closed • IO biomarker
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • IKZF1 (IKAROS Family Zinc Finger 1) • CSF1R (Colony stimulating factor 1 receptor)
    |
    TruSight RNA Pan-Cancer Panel
    |
    imatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • ifosfamide • etoposide IV • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Hemady (dexamethasone tablets) • Neupogen (filgrastim) • Starasid (cytarabine ocfosfate) • dexrazoxane
    5ms
    Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov)
    P3, N=280, Active, not recruiting, Children's Oncology Group | Trial completion date: Jun 2024 --> Jul 2025
    Trial completion date
    |
    GATA1 (GATA Binding Protein 1)
    |
    cytarabine • etoposide IV • daunorubicin • mitoxantrone • mercaptopurine • Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) • thioguanine • Kidrolase (L-asparaginase) • Leunase (L-asparaginase) • Spectrila (asparaginase Escherichia coli) • Starasid (cytarabine ocfosfate)
    5ms
    The ubiquitin ligase UBR4 and the deubiquitylase USP5 modulate the stability of DNA mismatch repair protein MLH1. (PubMed, J Biol Chem)
    In consistence, UBR4 or USP5 deficiency affects the cellular response to nucleotide analog 6-TG, supporting their roles in regulating mismatch repair. Our study has revealed important insights into the regulatory mechanisms underlying MLH1 proteolysis, critical to DNA mismatch repair related diseases.
    Journal • Mismatch repair
    |
    MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • USP5 (Ubiquitin Specific Peptidase 5)
    |
    thioguanine
    5ms
    Innovating Thiopurine Therapeutic Drug Monitoring: A Systematic Review and Meta-Analysis on DNA-Thioguanine Nucleotides (DNA-TG) as an Inclusive Biomarker in Thiopurine Therapy. (PubMed, Clin Pharmacokinet)
    This systematic review strongly supports the further investigation of DNA-TG as a marker for monitoring thiopurine therapy. Its correlation with treatment outcomes, such as relapse-free survival in ALL and the risk of leukopenia in IBD, underscores its role in enhancing personalized treatment approaches. DNA-TG effectively identifies NUDT15 variants and predicts late leukopenia in patients with IBD, regardless of their NUDT15 variant status. The recommended threshold for late leukopenia prediction in patients with IBD with DNA-TG is suggested to be between 320 and 340 fmol/µg DNA. More clinical research on DNA-TG implementation is mandatory to improve patient care and to improve inclusivity in thiopurine treatment.
    Retrospective data • Review • Journal
    |
    NT5C2 (5'-Nucleotidase Cytosolic II) • ITPA (Inosine Triphosphatase) • NUDT15 (Nudix Hydrolase 15)
    |
    mercaptopurine • thioguanine
    7ms
    Chemotherapy in pediatric low-grade gliomas (PLGG). (PubMed, Childs Nerv Syst)
    The carboplatin and vincristine (CV) combination stands as a standard systemic therapy for PLGG, varying in dosage and administration between North America and Europe...Vinblastine has emerged as another effective regimen with minimal toxicity. TPCV, a regimen combining thioguanine, procarbazine, lomustine, and vincristine, was compared to CV in a Children's Oncology Group trial, showing comparable outcomes, but more toxicity. Vinorelbine, temozolomide, and metronomic chemotherapy have also been explored, with varied success rates and toxicity profiles...The landscape of chemotherapy in PLGG is evolving, with a growing focus on molecular subtyping and targeted therapies. Understanding the role of chemotherapy in conjunction with novel treatments is crucial for optimizing outcomes in pediatric patients with low-grade gliomas.
    Journal
    |
    BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    carboplatin • temozolomide • vincristine • vinorelbine tartrate • lomustine • Matulane (procarbazine hydrochloride) • vinblastine • thioguanine
    8ms
    Adding Targeted Drugs to Usual Chemotherapy for Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LBL) (clinicaltrials.gov)
    P2, N=0, Withdrawn, National Cancer Institute (NCI) | N=154 --> 0 | Not yet recruiting --> Withdrawn
    Enrollment change • Trial withdrawal
    |
    Venclexta (venetoclax) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • methotrexate • vincristine • daunorubicin • navitoclax (ABT 263) • Oncaspar liquid (pegaspargase) • nelarabine • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
    8ms
    Adding Dasatinib Or Venetoclax To Improve Responses In Children With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) Or Lymphoma (T-LLY) Or Mixed Phenotype Acute Leukemia (MPAL) (clinicaltrials.gov)
    P2, N=145, Not yet recruiting, St. Jude Children's Research Hospital
    New P2 trial
    |
    Venclexta (venetoclax) • dasatinib • cytarabine • bortezomib • cyclophosphamide • vincristine • daunorubicin • nelarabine • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine
    8ms
    Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (clinicaltrials.gov)
    P2, N=171, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2024 --> Jul 2024
    Trial initiation date • Combination therapy
    |
    MCL1 (Myeloid cell leukemia 1) • KMT2A (Lysine Methyltransferase 2A) • BCL2L1 (BCL2-like 1)
    |
    BCL2 expression
    |
    Venclexta (venetoclax) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate) • prednisolone
    8ms
    Adding Targeted Drugs to Usual Chemotherapy for Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LBL) (clinicaltrials.gov)
    P2, N=154, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2024 --> Aug 2024
    Trial initiation date
    |
    Venclexta (venetoclax) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • methotrexate • vincristine • daunorubicin • navitoclax (ABT 263) • Oncaspar liquid (pegaspargase) • nelarabine • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
    8ms
    A Study Comparing the Combination of Dasatinib and Chemotherapy Treatment With or Without Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or Philadelphia Chromosome-Like (Ph-Like) ABL-Class B-Cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov)
    P3; Initiation date: Apr 2024 --> Jul 2024
    Trial initiation date
    |
    ABL1 (ABL proto-oncogene 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CD19 (CD19 Molecule) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor)
    |
    CD19 expression
    |
    TruSight RNA Pan-Cancer Panel
    |
    dasatinib • imatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Starasid (cytarabine ocfosfate)
    8ms
    Inotuzumab Ozogamicin and Frontline Chemotherapy in Treating Young Adults With Newly Diagnosed B Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P3, N=310, Suspended, Alliance for Clinical Trials in Oncology | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Mar 2024 --> Mar 2025
    Trial completion date • Trial primary completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD20 (Membrane Spanning 4-Domains A1) • CD22 (CD22 Molecule) • ITGB1 (Integrin Subunit Beta 1)
    |
    CD20 positive • CD22 positive
    |
    Rituxan (rituximab) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Besponsa (inotuzumab ozogamicin) • vincristine • daunorubicin • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine
    9ms
    Ocular pharmacological and biochemical profiles of 6-thioguanine: a drug repurposing study. (PubMed, Front Pharmacol)
    6TG evidenced a marked anti-angiogenic activity in HUVECs exposed to high glucose and in mice with DR. This seems to be mediated by MC1R and MC5R retinal receptors.
    Journal
    |
    CD34 (CD34 molecule)
    |
    thioguanine
    9ms
    AALL0434: Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma (clinicaltrials.gov)
    P3, N=1895, Active, not recruiting, National Cancer Institute (NCI)
    Trial completion date
    |
    CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • CD22 (CD22 Molecule) • CD34 (CD34 molecule) • CD5 (CD5 Molecule) • CD7 (CD7 Molecule) • CD2 (CD2 Molecule) • MPO (Myeloperoxidase)
    |
    CD22 expression
    |
    cytarabine • doxorubicin hydrochloride • cyclophosphamide • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • nelarabine • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Kidrolase (L-asparaginase) • Leunase (L-asparaginase) • Spectrila (asparaginase Escherichia coli) • Starasid (cytarabine ocfosfate) • dexamethasone injection
    9ms
    Ma-Spore ALL 2020 Study (clinicaltrials.gov)
    P2, N=500, Recruiting, National University Hospital, Singapore
    New P2 trial
    |
    dasatinib • Rituxan (rituximab) • imatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • vincristine • fludarabine IV • mercaptopurine • thioguanine
    9ms
    Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (clinicaltrials.gov)
    P2, N=171, Not yet recruiting, National Cancer Institute (NCI)
    New P2 trial • Combination therapy
    |
    MCL1 (Myeloid cell leukemia 1) • KMT2A (Lysine Methyltransferase 2A) • BCL2L1 (BCL2-like 1)
    |
    BCL2 expression
    |
    Venclexta (venetoclax) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate) • prednisolone
    10ms
    A Study Comparing the Combination of Dasatinib and Chemotherapy Treatment With or Without Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or Philadelphia Chromosome-Like (Ph-Like) ABL-Class B-Cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov)
    P3; Initiation date: Jan 2024 --> Apr 2024
    Trial initiation date
    |
    ABL1 (ABL proto-oncogene 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CD19 (CD19 Molecule) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor)
    |
    CD19 expression
    |
    TruSight RNA Pan-Cancer Panel
    |
    dasatinib • imatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Starasid (cytarabine ocfosfate)
    10ms
    Polyamine Inhibitor SAM486A Augments Cytarabine Cytotoxicity in Methylthioadenosine Phosphorylase-deficient Leukemia Cells. (PubMed, Anticancer Res)
    Methionine metabolism and polyamine synthesis can be attractive therapeutic targets in leukemia.
    Journal
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    cytarabine • methotrexate • clofarabine • thioguanine
    10ms
    AALL1732: Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy (clinicaltrials.gov)
    P3, N=4997, Recruiting, Children's Oncology Group | Trial completion date: Jun 2029 --> Mar 2030 | Trial primary completion date: Jun 2029 --> Mar 2030
    Trial completion date • Trial primary completion date
    |
    cytarabine • doxorubicin hydrochloride • cyclophosphamide • methotrexate • Besponsa (inotuzumab ozogamicin) • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
    11ms
    An analysis pipeline for understanding 6-thioguanine effects on a mouse tumour genome. (PubMed, Cancer Immunol Immunother)
    We observed that the number of predicted neoepitopes were more accurate indicators of tumour immune control than TMB. In conclusion, this study demonstrates the usability of the proposed pipeline, and suggests it could be an essential robust genome analysis platform for future mouse genomic analysis.
    Preclinical • Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    thioguanine
    11ms
    Adding Targeted Drugs to Usual Chemotherapy for Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LBL) (clinicaltrials.gov)
    P2, N=154, Not yet recruiting, National Cancer Institute (NCI)
    New P2 trial
    |
    Venclexta (venetoclax) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • methotrexate • vincristine • daunorubicin • navitoclax (ABT 263) • Oncaspar liquid (pegaspargase) • nelarabine • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
    1year
    Systematic Literature Review of Incidence and Management of Non-HCT-Related Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) (ASH 2023)
    One study reported outcomes for 206 children who received supportive care for VOD/SOS during 6-thioguanine therapy for ALL; only three pts had acute hepatic failure and all pts recovered from VOD/SOS. Non-HCT VOD/SOS occurs in diverse disease areas, including hematologic and solid tumor cancers. A lack of consensus regarding VOD/SOS diagnosis in the non-HCT setting may lead to underdiagnosis; therefore, clinicians should be vigilant for VOD/SOS even in non-HCT pts. Though defibrotide is approved for post-HCT VOD/SOS, there is no approved therapy for non-HCT VOD/SOS; future trials should focus on diagnosis and treatment outside the HCT setting, which represents a significant unmet need.
    Review
    |
    thioguanine • Defitelio (defibrotide)
    1year
    The Role of Small Nucleolar RNAs As Putative Biomarkers of Chemoresistance in Pediatric Acute Lymphoblastic Leukemia (ASH 2023)
    05 and absolute log2FC>1) in the high-resistance group for one or multiple drugs: amsacrine (ams, n = 10), etoposide (eto, n = 10), tioguanine (thio, n = 8) and mitoxantrone (mito, n = 1). Importantly, our analysis indicates that the differential expression of snoRNAs in the resistance groups cannot be solely attributed to host gene expression, implying that targeting pathways involving host genes might not be the most effective approach. Rather than concentrating on pathways involving host genes, our results suggest that understanding the mechanisms of action of snoRNAs could provide promising avenues for developing novel therapeutic targets to enhance drug response in pediatric ALL.
    Clinical
    |
    SNHG1 (Small Nucleolar RNA Host Gene 1)
    |
    etoposide IV • mitoxantrone • thioguanine • Amsidine (amsacrine)
    1year
    AALL1731: A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia (clinicaltrials.gov)
    P3, N=6720, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2030 --> Jun 2029 | Trial primary completion date: Mar 2030 --> Jun 2029
    Trial completion date • Trial primary completion date
    |
    cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • leucovorin calcium • Oncaspar liquid (pegaspargase) • Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) • thioguanine • Hemady (dexamethasone tablets) • Purixan (mercaptopurine oral suspension) • Starasid (cytarabine ocfosfate)
    1year
    Ruxolitinib and Chemotherapy in Adolescents and Young Adults With Ph-like Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P1, N=15, Recruiting, University of Chicago | Trial completion date: Sep 2024 --> Sep 2027 | Trial primary completion date: Sep 2023 --> Sep 2026
    Trial completion date • Trial primary completion date
    |
    JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • IL7R (Interleukin 7 Receptor) • SH2B3 (SH2B Adaptor Protein 3)
    |
    CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 rearrangement • SH2B3 deletion
    |
    Rituxan (rituximab) • cytarabine • doxorubicin hydrochloride • Jakafi (ruxolitinib) • cyclophosphamide • vincristine • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine
    1year
    SERS spectroscopy as a tool for the study of thiopurine drug pharmacokinetics in a model of human B leukemia cells. (PubMed, Chem Biol Interact)
    The aim of this study is to investigate mercaptopurine and thioguanine pharmacokinetics by SERS in cell lysates of a B-lymphoblastoid cell line (NALM-6), that did (TPMT*1) or did not (MOCK) overexpress the wild-type form of TPMT as an in vitro cellular lymphocyte model to discriminate between cells with different levels of TPMT activity on the base of the amount of thioguanosine nucleotides (TGN) metabolites formed. A strong positive correlation (Spearman's rank correlation coefficient rho = 0.96) exists between absolute quantification of TGMP (pmol/1x10 cells), obtained by LC-MS/MS, and SERS signal (intensity of TGN at 915 cm). In future studies, we aim to apply this method to investigate TPMT activity in patients' leukocytes.
    PK/PD data • Journal
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    TPMT (Thiopurine S-Methyltransferase)
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    mercaptopurine • thioguanine
    1year
    A Study Comparing the Combination of Dasatinib and Chemotherapy Treatment With or Without Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or Philadelphia Chromosome-Like (Ph-Like) ABL-Class B-Cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov)
    P3; N=680; Not yet recruiting; Sponsor:National Cancer Institute (NCI)
    New P3 trial
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    ABL1 (ABL proto-oncogene 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CD19 (CD19 Molecule) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor)
    |
    CD19 expression
    |
    TruSight RNA Pan-Cancer Panel
    |
    dasatinib • imatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Starasid (cytarabine ocfosfate)
    1year
    AALL1731: A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia (clinicaltrials.gov)
    P3, N=6720, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting
    Enrollment open • Combination therapy
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    cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • leucovorin calcium • Oncaspar liquid (pegaspargase) • Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) • thioguanine • Hemady (dexamethasone tablets) • Purixan (mercaptopurine oral suspension) • Starasid (cytarabine ocfosfate)
    1year
    AALL1231: Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma (clinicaltrials.gov)
    P3, N=847, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2023 --> Sep 2024
    Trial completion date
    |
    CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • CD22 (CD22 Molecule) • CD34 (CD34 molecule) • CD5 (CD5 Molecule) • CD7 (CD7 Molecule) • CD2 (CD2 Molecule) • MPO (Myeloperoxidase)
    |
    CD22 expression
    |
    cytarabine • bortezomib • doxorubicin hydrochloride • cyclophosphamide • ifosfamide • etoposide IV • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
    1year
    AALL15P1: Azacitidine and Combination Chemotherapy in Treating Infants With Acute Lymphoblastic Leukemia and KMT2A Gene Rearrangement (clinicaltrials.gov)
    P2, N=78, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Sep 2024
    Trial completion date
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
    |
    cytarabine • cyclophosphamide • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
    1year
    AALL1131: Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations (clinicaltrials.gov)
    P3, N=5937, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Sep 2024
    Trial completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6)
    |
    MLL rearrangement • MLL rearrangement
    |
    dasatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • methotrexate • vincristine • daunorubicin • clofarabine • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)