In relapse/refractory (R/R) patients, standard of care treatments, including nelarabine, yield response rate of about 20-40% and responses are of short duration...For example, TTOs included Tofacitinib and Venetoclax (Tofa/Ven) in case of IL7R (CD127) expression or IL7R-pathway alterations (IL7RALT), 5-azacytidine and Venetoclax (Aza/Ven) in case of T-ALL/LL with epigenetic regulators alterations (DNMT3A, ASXL1, PHF6, TET2, PRC2, IDH1/2, SRSF2...) or Temsirolimus, Erwinase and Venetoclax (Tem/Erw/Ven) in case of PI3K signaling pathway alterations (PI3KALT)...Twenty-five patients received a TTO, including 14 Aza/Ven (56%), 8 Tofa/Ven (32%), 2 Tem/Erw/Ven (8%) and 1 Trametinib/Ven (4%)...A better knowledge of the oncogenetic landscape of T-ALL, and a close collaboration between clinicians and biologists, resulted in individualized treatment strategies. With a 3 months cumulative incidence of response of 70%, TTOs appear to be a promising approach in R/R T-ALL.

1 year ago

IO biomarker

TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATM (ATM serine/threonine kinase) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • IL7R (Interleukin 7 Receptor) • PHF6 (PHD Finger Protein 6)

TP53 mutation • ATM mutation • BCL2 expression • IL7R expression

Venclexta (venetoclax) • Mekinist (trametinib) • azacitidine • Torisel (temsirolimus) • nelarabine • tofacitinib • Erwinase (erwinia L-asparaginase)

1year

Back to the future: the amazing journey of the therapeutic antileukemia enzyme asparaginase Erwinia chrysanthemi. (PubMed, Haematologica)

An asparaginase product displaying the same characteristics of the Erwinia chrysanthemi asparaginase recently has been produced by use of recombinant technology, thus securing a preparation available for use as an alternative, or as a back-up in case of shortages, for the non-recombinant product. The long journey of the Erwinia chrysanthemi asparaginase product as it has developed throughout the last several decades has made it possible for almost every child and adult with ALL to complete the asparaginase-based protocol treatment when an immunological reaction has occurred to any Escherichia coli asparaginase product.

1 year ago

Journal

Erwinase (erwinia L-asparaginase)

1year

A Phase 1, Single Centre, Open Label, Single Dose, Pharmacokinetic Study of Erwinaze in Healthy Adult Volunteers (ACTRN12623000491662)

P1, N=12, Not yet recruiting, Porton Biopharma Limited

1 year ago

New P1 trial

Erwinase (erwinia L-asparaginase)

over1year

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

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

over 1 year ago

Enrollment closed

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)

CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 fusion • SH2B3 deletion

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

over2years

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

P2, N=170, Recruiting, Incyte Corporation | Trial completion date: Dec 2024 --> Sep 2025 | Trial primary completion date: Dec 2024 --> Sep 2025

over 2 years ago

Trial completion date • Trial primary completion date

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)

CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 fusion • SH2B3 deletion

over2years

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov)

P3, N=312, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2025 --> Jun 2024 | Trial primary completion date: Sep 2025 --> Jun 2024

over 2 years ago

Trial completion date • Trial primary completion date

GATA1 (GATA Binding Protein 1)

cytarabine • etoposide IV • daunorubicin • mitoxantrone • thioguanine • Erwinase (erwinia L-asparaginase)

over2years

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov)

P3, N=312, Active, not recruiting, Children's Oncology Group | Recruiting --> Active, not recruiting

over 2 years ago

Enrollment closed

GATA1 (GATA Binding Protein 1)

cytarabine • etoposide IV • daunorubicin • mitoxantrone • thioguanine • Erwinase (erwinia L-asparaginase)

over2years

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov)

P3, N=312, Recruiting, Children's Oncology Group | Trial primary completion date: Jun 2023 --> Sep 2025

over 2 years ago

Trial primary completion date

GATA1 (GATA Binding Protein 1)

cytarabine • etoposide IV • daunorubicin • mitoxantrone • thioguanine • Erwinase (erwinia L-asparaginase)

over2years

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

P2, N=170, Recruiting, Incyte Corporation | Trial primary completion date: Feb 2024 --> Dec 2024

over 2 years ago

Trial primary completion date

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)

CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 fusion • SH2B3 deletion

3years

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

P2, N=170, Recruiting, Incyte Corporation | Trial completion date: May 2024 --> Dec 2024

3 years ago

Clinical • Trial completion date

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)

CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 fusion • SH2B3 deletion

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

almost4years

Venetoclax and pegcrisantaspase for complex karyotype acute myeloid leukemia. (PubMed, Leukemia)

Here, we report synergistic anti-leukemic activity of the BCL-2 inhibitor venetoclax (Ven) and the asparaginase formulation Pegylated Crisantaspase (PegC) in CK-AML in vitro and in vivo...Superiority of Ven-PegC, compared to single drugs, and, importantly, the clinically utilized Ven-azacitidine combination, was also demonstrated in vivo in CK-AML...In vivo, Ven-PegC treatment completely depleted plasma glutamine and asparagine and inhibited mRNA translation and cellular protein synthesis. Since this novel mechanistically-rationalized regimen combines two drugs already in use in acute leukemia treatment, we plan a clinical trial of the Ven-PegC combination in relapsed/refractory CK-AML.

almost 4 years ago

Journal

MCL1 (Myeloid cell leukemia 1) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)

MCL1 expression

Venclexta (venetoclax) • azacitidine • Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) • Erwinase (erwinia L-asparaginase)

4years

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov)

P3, N=256, Recruiting, Children's Oncology Group | Trial primary completion date: Mar 2023 --> Jun 2023

4 years ago

Clinical • Trial primary completion date

GATA1 (GATA Binding Protein 1)

cytarabine • etoposide IV • daunorubicin • mitoxantrone • mercaptopurine • thioguanine • Erwinase (erwinia L-asparaginase) • Kidrolase (L-asparaginase) • Spectrila (asparaginase Escherichia coli)

4years

A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations (clinicaltrials.gov)

P3, N=1400, Recruiting, Children's Oncology Group | Trial completion date: Feb 2025 --> Sep 2027 | Trial primary completion date: Feb 2025 --> Sep 2027

4 years ago

Clinical • Trial completion date • Trial primary completion date

FLT3 (Fms-related tyrosine kinase 3)

Xospata (gilteritinib) • etoposide IV • methotrexate • Mylotarg (gemtuzumab ozogamicin) • Vyxeos (cytarabine/daunorubicin liposomal formulation) • mitoxantrone • Erwinase (erwinia L-asparaginase) • Kidrolase (L-asparaginase) • Spectrila (asparaginase Escherichia coli) • dexrazoxane

over4years

A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations (clinicaltrials.gov)

P3, N=1400, Recruiting, Children's Oncology Group | Not yet recruiting --> Recruiting

over 4 years ago

Clinical • Enrollment open

FLT3 (Fms-related tyrosine kinase 3)

over4years

A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations (clinicaltrials.gov)

P3, N=1400, Not yet recruiting, Children's Oncology Group

over 4 years ago

Clinical • New P3 trial

FLT3 (Fms-related tyrosine kinase 3)