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Report for Clinical Trial NCT02518750

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase II Study Incorporating Panobinostat, Bortezomib and Liposomal Vincristine Into Re-Induction Therapy for Relapsed Pediatric T-Cell Acute Lymphoblastic Leukemia or Lymphoma

This is a phase-II study to evaluate the efficacy of a salvage regimen in children with relapsed T-cell ALL or lymphoma. Peg-asparaginase, mitoxantrone, intrathecal triples (IT) (intrathecal methotrexate/hydrocortisone/cytarabine) (ITMHA) and dexamethasone are commonly used drugs to treat relapsed or refractory acute lymphocytic leukemia or lymphoma (ALL). In this study, the investigators want to know if adding three drugs called panobinostat, bortezomib and liposomal vincristine (VSLI) to this regimen will result in remission (no signs or symptoms of leukemia or lymphoma). - Panobinostat has been approved by the FDA for treating adults with multiple myeloma, but it has not been approved for use in children and has not been given together with the other drugs used in this study. It has not been widely studied in children. - VSLI has been approved by the FDA for adults with relapsed or refractory ALL, but has not yet been approved for treating children with leukemia or lymphoma. - Bortezomib has been approved by the FDA for treating adults with a cancer called multiple myeloma and adults with relapsed mantle cell lymphoma; it has not been approved for treating children. PRIMARY OBJECTIVE: - To estimate the complete remission (CR) rate for patients with T-cell lymphoblastic leukemia and lymphoma in first relapse. SECONDARY OBJECTIVES: - To evaluate minimal residual disease (MRD) levels at end of each block of therapy. - To describe the toxicities of vincristine sulfate liposome injection (VSLI) when used in combination with chemotherapy and bortezomib.

NCT02518750 Acute Lymphoblastic Leukemia Lymphoma, Non-Hodgkin's Leukemia, T-Cell Leukemia, B-Cell
MeSH: Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Lymphoma, Non-Hodgkin Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Leukemia, B-Cell Leukemia, T-Cell
HPO: Leukemia Lymphoid leukemia Lymphoma Non-Hodgkin lymphoma T-cell acute lymphoblastic leukemias

14 Interventions

Name: Dexamethasone

Description: Given orally (PO).

Type: Drug

Study Participants

Name: Panobinostat

Description: Given PO.

Type: Drug

Study Participants

Name: Liposomal vincristine

Description: For intravenous (IV) use only.

Type: Drug

Study Participants

Name: Mitoxantrone

Description: Given IV.

Type: Drug

Study Participants

Name: Peg-asparaginase

Description: Given IV or intramuscularly (IM). In case of allergy or intolerance to Peg-asparaginase, Erwinia L-asparaginase (Erwinase®) will be used. Erwinia L-asparaginase is given by either IV or IM injection.

Type: Drug

Study Participants

Name: Bortezomib

Description: Given by IV push over 3 to 5 seconds. For IV use only.

Type: Drug

Study Participants

Name: Intrathecal Triples

Description: Given IT as ITMHA.

Type: Drug

Study Participants

Name: High-dose methotrexate

Description: Given intrathecally (IT) or IV.

Type: Drug

Study Participants

Name: 6-Mercaptopurine

Description: Given PO at consistent time each day.

Type: Drug

Study Participants

Name: High-dose cytarabine

Description: Given IT or IV.

Type: Drug

Study Participants

Name: Nelarabine

Description: Given IV

Type: Drug

Study Participants

Name: Cyclophosphamide

Description: Given IV.

Type: Drug

Study Participants

Name: Etoposide

Description: Given IV. In case of etoposide reactions, IV etoposide phosphate (Etopophos®) will be used.

Type: Drug

Study Participants

Name: Clofarabine

Description: Given IV. Clofarabine will be given instead of nelarabine for patients with B-lymphoblastic leukemia and lymphoma in stratum II.

Type: Drug

Study Participants


Primary Outcomes

Description: All participants who start re-induction Block A therapy are considered evaluable. Any patient who at any time point achieves CR and goes to transplant is considered as a success; or any patient who successfully reaches the end of block C and achieves/remains in CR is considered a success; all other cases are considered as failure.

Measure: Complete Remission (CR) Rate

Time: At the end of each remission re-induction block C (approximately 13 weeks after start of therapy)

Secondary Outcomes

Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.

Measure: Block A Minimal Residual Disease (MRD)

Time: At the end of Block A therapy (approximately 5 weeks after start of therapy)

Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.

Measure: Block B Minimal Residual Disease (MRD)

Time: At the end of Block B therapy (approximately 10 weeks after start of therapy)

Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.

Measure: Block C Minimal Residual Disease (MRD)

Time: At the end of Block C therapy (approximately 13 weeks after start of therapy)

Description: The toxicities of liposomal vincristine (VSLI) when used in combination with chemotherapy will be evaluated. Proportions (probabilities) of relevant toxicities will be estimated with point and interval estimates.

Measure: Proportion of Relevant Toxicities

Time: At the completion of therapy (up to approximately 5 months after the start of therapy)

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 Q12H

Additional ITs on Days 10 and 17 for patients with central nervous system (CNS) 2, 3 or traumatic tap with blasts Block B: approximately 5 weeks - High-dose methotrexate 8 g/m^2 IV over 24 hours (will not be given to patients with prior cranial irradiation) Day 1 - 6-mercaptopurine 50 mg/m^2 PO days 1-14 - ITMHA Day 1 - High-dose cytarabine 3 g/m^2 IV every 12 hours (Q12H) Days 15 and 16 Block C: approximately 3 weeks - Nelarabine 650 mg/m^2/day IV Days 1-5 (Clofarabine 40 mg/m^2/day IV Days 1-5 will be given instead of nelarabine for patients with B-lymphoblastic leukemia and lymphoma in stratum II) - Cyclophosphamide 300 mg/m^2 IV Days 1-5 - Etoposide 100 mg/m^2/day IV Days 1-5 Response evaluation is performed after the end of each treatment block. --- Q12H ---



HPO Nodes


HPO:
Leukemia
Genes 190
ATM KRAS KIT RPS15A NF1 MPL RPL35A RPL11 RPL18 DDX41 SBDS LPP ETV6 BUB1B F13A1 DNMT3A JAK2 NUP214 FANCD2 MSH6 FANCA PIGL NRAS TCIRG1 BUB1 TET2 FLT3 TAL1 ATRX TREX1 PDGFRA SRP54 RPS29 PTPN11 CALR FANCE WIPF1 SF3B1 GATA2 GLI1 STS SH3GL1 XRCC4 MPL SH2B3 EFL1 PIGA TREM2 CBL MPL RUNX1 MPL PIGL THPO FANCG NSD1 BRD4 NSUN2 SH2B3 RARA GATA2 NPM1 CBL CHIC2 ERBB3 GFI1 TERT KIT BCR ARHGAP26 DYNC2LI1 EVC SCN10A GATA1 ELANE RNASEH2B RPS14 SH2B3 JAK2 RPL15 SBDS NRAS RPL26 RPL27 ADA2 RPS7 TYROBP F13B MSH2 BCR WAS TERC TP53 TRIP13 MYD88 NUTM1 RPS24 GNB1 TP53 DNMT3A TERT NUMA1 NUP214 RPL5 SAMD9L TET2 CFTR POT1 FANCC RPS10 EP300 EVC2 BUB1B CEBPA BRCA2 DNAJC21 CALR SCN9A LIG4 ADAR BLM TET2 JAK2 SMPD1 RNASEH2C SCN11A GATA2 BUB3 PRSS1 KIF11 BCR RPL35 TAL2 SRP54 IFIH1 ABL1 PDGFRB KRAS RNASEH2A TET2 MLLT10 SRP54 DNAJC21 DKC1 RUNX1 APC LIG4 CBFB BLM THPO CALR NBN JAK2 MLH1 RPS19 ELANE SAMD9L RPL31 PMS2 ASXL1 TSR2 MLF1 PIK3CA DNAJC21 RUNX1 GFI1 SRSF2 SETBP1 HAX1 RPS26 RPS17 FLT3 RPS27 PIK3R1 KRAS CEP57 PICALM CREBBP GATA2 CTRC MYD88 TET2 RPS28 ABL1 RB1 SPINK1 GATA1 NBN JAK2 SAMHD1
Lymphoid leukemia
Lymphoma
Genes 133
ATM KRAS CD19 IGH DDX41 BCL10 BIRC3 FOXP1 MS4A1 TP63 RAG1 LIG4 NFKB2 MSH6 TERC RECQL4 NTHL1 WIPF1 CTC1 LYST NOP10 RASGRP1 TNFRSF1B XRCC4 PRKCD NHP2 MAGT1 TNFRSF13B IGH RMRP RUNX1 CTLA4 DCLRE1C FAS ICOS RNF43 NSUN2 XIAP IL7R CASP10 BCL6 CDKN2A ATM IL2RG RTEL1 PARN NBN KIT TNFRSF13C TCF4 ICOS TNFSF12 CHEK2 USB1 CD19 CR2 NRAS MSH2 WAS BCL10 CASP10 MYD88 COL14A1 PRKCD TNFRSF13B MYC MDM2 SH2D1A CCND1 BCL10 CFTR CD27 PGM3 TCF4 CHD7 IGH LIG4 BLM BCL2 TET2 HLA-DRB1 PRSS1 NPM1 KIF11 ITK WRAP53 RAD54B TINF2 FAS DKC1 APC CD81 LIG4 BLM CD28 DKC1 AAGAB RAG2 TNFRSF1B MLH1 TNFRSF13C DNASE1L3 NFKB1 PMS2 ASXL1 IL2RG PRF1 PTEN MALT1 RAD54L CTLA4 CD28 PNP SRSF2 TNFSF12 STAT3 POLE ADA CR2 ADA FASLG PIK3R1 TP53 CTRC ZAP70 MYD88 RB1 RMRP SPINK1 TERT KLHDC8B NBN RHOH
Non-Hodgkin lymphoma
Genes 32
ATM FAS CASP10 CTLA4 FAS BCL10 CD28 BIRC3 FOXP1 TNFRSF1B MYC CCND1 ASXL1 ATM MALT1 CTLA4 CD28 SRSF2 KIT POLE IGH ADA TET2 FASLG PIK3R1 NTHL1 RASGRP1 TNFRSF1B PRKCD NBN RHOH IGH
T-cell acute lymphoblastic leukemias
Genes 1
BRCA2