These degraders, in conjunction with orthogonal CRISPR knock-out and reconstitution experiments, support a non-enzymatic role for NUDT5 in modulating the cellular response to 6-TG. Depletion of NUDT5 protein is antagonistic to NUDT15 inhibition, suggesting a distinct mode-of-action with potential implications for patient therapy.

1 month ago

Journal

NUDT15 (Nudix Hydrolase 15)

thioguanine

2ms

Severe Thiopurine-Induced Myelosuppression in a Pediatric Acute Lymphoblastic Leukemia Patient With the NUDT15 *1/*6 Genotype: A Brief Report. (PubMed, Clin Transl Sci)

After 75 mg/m2/day mercaptopurine, myelosuppression necessitated a three-week delay prior to the next phase of therapy. With 60 mg/m2/day thioguanine in a subsequent phase of therapy, she was admitted twice for fever and neutropenia...In a larger cohort sequenced for suspicion of rare genetic disease, the frequency of NUDT15*6 was 0.15% among 1011 unrelated individuals. This brief report supports the recent update that patients with the NUDT15*1/*6 genotype should be classified as intermediate metabolizers.

2 months ago

Journal

NUDT15 (Nudix Hydrolase 15)

mercaptopurine • thioguanine

2ms

Testing Blinatumomab With or Without Revumenib in Patients With B-cell Acute Lymphoblastic Leukemia With a Genetic Change Requiring More Treatment (clinicaltrials.gov)

P2, N=90, Not yet recruiting, SWOG Cancer Research Network

2 months ago

New P2 trial

CD19 (CD19 Molecule) • KMT2A (Lysine Methyltransferase 2A)

clonoSEQ®

cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • Revuforj (revumenib) • leucovorin calcium • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)

2ms

6-Mercaptopurine metabolic profiles and clinical outcomes in TPMT and NUDT15 phenotypes during maintenance therapy for Thai paediatric acute lymphoblastic leukaemia. (PubMed, Br J Clin Pharmacol)

The TPMT and NUDT15 genes influence the side effects of 6-MP medications. Patients who have variations in both genes are at a higher risk of experiencing toxicity. High levels of 6-TGN are associated with TPMT variants, whereas low levels are linked to NUDT15 variants. This could facilitate more precise monitoring of toxicity.

2 months ago

Clinical data • Journal

NUDT15 (Nudix Hydrolase 15)

mercaptopurine • thioguanine

2ms

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, Completed, National Cancer Institute (NCI) | Trial completion date: Oct 2026 --> Mar 2026 | Active, not recruiting --> Completed

2 months ago

Trial completion • 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

dasatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • methotrexate • vincristine • daunorubicin • clofarabine • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)

3ms

AALL0932: Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma (clinicaltrials.gov)

P3, N=9350, Completed, Children's Oncology Group | Active, not recruiting --> Completed

3 months ago

Trial completion

cytarabine • doxorubicin hydrochloride • cyclophosphamide • methotrexate • vincristine • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)

3ms

LBL 2018: International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma (clinicaltrials.gov)

P3, N=683, Recruiting, University Hospital Muenster | Trial completion date: Nov 2027 --> Apr 2030 | Trial primary completion date: Nov 2027 --> Apr 2030

3 months ago

Trial completion date • Trial primary completion date

cytarabine • doxorubicin hydrochloride • cyclophosphamide • ifosfamide • vincristine • prednisone • daunorubicin • mercaptopurine • thioguanine • vindesine

3ms

ALLIANCE: Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia (clinicaltrials.gov)

P2, N=318, Completed, Alliance for Clinical Trials in Oncology | Active, not recruiting --> Completed

3 months ago

Trial completion

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

cytarabine • doxorubicin hydrochloride • cyclophosphamide • vincristine • daunorubicin • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine

4ms

Rux-cALL-Pol 2020: Single-arm interventional study with ruxolitinib and AIEOP-BFM 2017 Poland or AIEOP-BFM 2017 standard of care chemotherapy in children with acute lymphoblastic leukemia and confirmed activation of JAK/STAT pathway. (2024-518316-39-00)

P2/3, N=25, Recruiting, Medical University Of Lodz | Not yet recruiting --> Recruiting

4 months ago

Enrollment open

JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • AFF1 (AF4/FMR2 Family Member 1) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)

KMT2A rearrangement

cytarabine • doxorubicin hydrochloride • Jakafi (ruxolitinib) • cyclophosphamide • ifosfamide • etoposide IV • vincristine • daunorubicin • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • vindesine

4ms

AALL0932: Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma (clinicaltrials.gov)

P3, N=9350, Active, not recruiting, Children's Oncology Group | Trial completion date: Mar 2028 --> Mar 2026

4 months ago

Trial completion date

4ms

A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov)

P2, N=222, Recruiting, National Cancer Institute (NCI) | Phase classification: P3 --> P2

4 months ago

Phase classification

ABL1 (ABL proto-oncogene 1) • CD19 (CD19 Molecule) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor)

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)

5ms

AALL1521: A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia (clinicaltrials.gov)

P2, N=171, Completed, Incyte Corporation | Active, not recruiting --> Completed

5 months ago

Trial completion

JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • JAK1 (Janus Kinase 1) • IL7R (Interleukin 7 Receptor) • EPOR (Erythropoietin Receptor) • SH2B3 (SH2B Adaptor Protein 3)

cytarabine • doxorubicin hydrochloride • Jakafi (ruxolitinib) • cyclophosphamide • vincristine • prednisone • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Erwinase (erwinia asparaginase)