Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Venetoclax

For Part A (tuspetinib as a single agent), dose escalation cohort is planned up to 6 dose levels. If a subject in the dose escalation cohort at any dose level achieves clinical response then the dose level will continue to enroll in Part B. If one DLT or less is observed in the 6 patients (\<1/6 DLT observed) in Part A, up to 20 evaluable patients can be enrolled in Part B at that dose level.

For Part B (tuspetinib as a single agent), dose exploration cohort is planned up to 4 dose levels.

Part C, dose expansion, consists of 2 arms (tuspetinib as a single agent or tuspetinib plus venetoclax). Patients will be randomly assigned to either arm based on the number of slots available. The initial tuspetinib dose for the single arm will be 120mg.

Part C, dose expansion, consists of 2 arms (tuspetinib or tuspetinib plus venetoclax). Patients will be randomly assigned to either arm based on the number of slots available. The initial tuspetinib dose for the combo arm will be 80mg.

Tuspetinib

Venetoclax will be given to patients in combo treatment group (Part C) either in 50 mg or 100 mg tablets

Venetoclax Oral Tablet

Rafael Bejar, MD, PhD

Pankit Vachhani, MD

Deepa Jeyakumar, MD

Carolyn Mulroney, MD

Eric Tam, MD

Gabriel Mannis, MD

Brian Jonas

Nikolai Podoltsev, MD

Nikolai Podoltsev, MD, PhD

Justin Watts, MD

Martha Arellano

Amir Fathi, MD

Harry Erba, MD

Studipto Mukherjee, MD

Uma Borate, MD

Naval Daver, Dr

Anish Puliyayil, MD

Steven Lane, MD

Hock-Choong Lai, MD

Shuhying Tan, MD

Carolyn Grove, MD

Uwe Platzbecker, MD

Jörg Westermann, MD

Sang-Kyun Sohn

Ho-Jin Shin

Jeong-Ok Lee

Yunksuk Choi, MD

Chul-Won Jung

Leanne Berkahn, MD

Leanna Berkahn, MD

Teresa Bernal

Carmen Martinez Chamorro, MD

Carmen Martinez Chammoro

Olga Salamero, MD

Olga Salamero

Maria Tormo, MD

Pau Montesinos, MD

Naval Daver, MD

A Phase 1/2, Open-label, Multicenter, Dose Escalation and Expansion Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Tuspetinib (HM43239) in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)

This is a Phase 1/2, open-label, multi-center study to assess the efficacy, safety, tolerability, pharmacokinetics, including recommended phase 2 dose (RP2D) of tuspetinib (HM43239) monotherapy in subjects with relapsed or treatment-refractory acute myeloid leukemia (AML). This study will also evaluate the safety, tolerability, and PK parameters of tuspetinib (HM43239) in combination with venetoclax when administered in patients with R/R AML

Three parts in the study - Part A (dose escalation, tuspetinib as a single agent), Part B (dose exploration, tuspetinib as a single agent), Part C (dose expansion, tuspetinib as a single agent and combo arm of tuspetinib with venetoclax)

Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1/2 Open Label, Multicenter, Dose Escalation and Expansion Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM43239 in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

To determine the recommended phase 2 dose based on safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) consideration

Determine the maximum tolerated dose at which no more than 1 out of 6 patients experience a dose-limiting toxicity or establish the safety of clinically effective dose below the MTD if the MTD is not reached.relapsed or treatment-refractory (R/R) AML

To determine the frequency and severity of drug-related adverse events across different dose levels when administered in patients with R/R AML

Determine the maximum tolerated dose of HM43239 in combination with venetoclax at which no more than 1 out of 6 patients experience a dose-limiting toxicity or establish the safety of clinically effective dose below the MTD if the MTD is not reached.relapsed or treatment-refractory (R/R) AML

To determine the frequency and severity of drug-related adverse events across different dose levels of HM43239 in combination with venetoclax when administered in patients with R/R AML

To investigate the rate of complete remission (CR), CR with partial hematologic recovery (CRh), CR with incomplete platelet recovery (CRp), CR with incomplete hematologic recovery (CRi), and partial remission (PR) of patients taking HM43239

To investigate the rate of complete remission (CR), CR with partial hematologic recovery (CRh), CR with incomplete platelet recovery (CRp), CR with incomplete hematologic recovery (CRi), and partial remission (PR) of patients taking HM43239 in combination with venetoclax

Pharmacokinetic variables including maximum plasma concentration (Cmax)

Pharmacokinetic variables including minimum plasma concentration (Cmin)

Pharmacokinetic variables including area under the curve (AUC)

Pharmacokinetic variables including volume of distribution

Pharmacokinetic variables including clearance

Determine PD variables by using a plasma inhibitory activity assay (PIA assay) examining the reduction in phospho-STAT5 and phospho-FLT3 in cell lines exposed to plasma from subjects treated in the study.

Aptose Biosciences Inc.

Immune System Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Lymphoma, B-Cell

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

B-cell Lymphoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Anti-Infective Agents

Obinutuzumab

Inotuzumab Ozogamicin

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Immunotoxins

Immunoconjugates

Immunologic Factors

30mg twice weekly (BIW) for induction phase (cycle1-2,28 days per cycle)

chidamide

400mg daily d1-14 induction phase (cycle1-2, 28 days per cycle)

0.6 mg/m2 on day 1 of cycle 1-2(28 days per cycle)

This study is a multicenter, prospective, interventional clinical trial aimed at recruiting relapsed/refractory Ph-ALL patients at multiple stem cell transplantation centers, including the Stem Cell Transplantation Center of the Chinese Academy of Medical Sciences Hematology Hospital. The anticipated enrollment is 42 subjects. The enrolled patients are planned to receive a treatment regimen of chidamide in combination with venetoclax and obinutuzumab. Patients who achieve remission will undergo allogeneic stem cell transplantation, followed by continued oral maintenance therapy with chidamide for one year post-transplantation based on the disease condition.

Relapsed/refractory Ph-ALL patients who meet the inclusion criteria and provide informed consent will be enrolled in the study. They will receive combination chemotherapy with chidamide, venetoclax, and obinutuzumab. After one treatment cycle, if the patient achieves complete remission (CR) and minimal residual disease (MRD) negativity, they will proceed to the preparatory phase for allogeneic stem cell transplantation. In cases where MRD remains positive after one cycle of chemotherapy, the same regimen will be repeated for an additional cycle, followed by re-evaluation. Once MRD negativity is achieved, the patient will enter the preparatory phase for allogeneic stem cell transplantation. After successful hematopoietic recovery post-transplantation (neutrophil count \>0.5×10\^9/L, platelet count \>50×10\^9/L), chidamide 10mg qd will be added for maintenance therapy, which will be continued for one year post-transplantation.

A Prospective Clinical Study of Bridging alloHSCT After Treatment With Obinutuzumab in Combination With Chidamide and Venetoclax in RR Ph-ALL and B-cell Lymphoma Patients

A Prospective, Single-arm Clinical Study of Bridging Allogeneic Stem Cell Transplantation After Treatment With Obinutuzumab in Combination With Chidamide and Venetoclax in Relapsed/Refractory Ph-ALL and B-cell Lymphoma Patients

One-year overall survival rate (OS) after allogeneic stem cell transplantation.

Complete remission (CR) rate following treatment with obinutuzumab in combination with chidamide and venetoclax.

One-year relapse-free survival (RFS) after allogeneic stem cell transplantation.

Incidence of graft-versus-host disease (GVHD) following allogeneic stem cell transplantation.

Minimal residual disease (MRD) clearance rate following chemotherapy.

Institute of Hematology & Blood Diseases Hospital, China

Director

Cytarabine

Azacitidine

Daunorubicin

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Enzyme Inhibitors

VA regimen: azacytidine, 75mg/m2, subcutaneously, on days 1-7; venetoclax, orally, once a day, 100mg, d1; 200mg, d2; 400mg, days 3-28.

DA regimen: daunorubicin (60mg/m2) on days 1-3, intraveneously injection, and cytarabine (100mg/m2) on days 1-7, intraveneously injection, for 1 cycle.

Su-ning Chen

Suning Chen

Zhou-lin Lu

This is an open-label, multicenter, phase 2b, randomized study aiming to compare the efficacy and safety of venetoclax plus azacytidine Versus daunorubicin plus cytarabine (conventional 7+3 regimen) in adult acute myeloid leukemia (AML) patients with adverse risk featuress. Participants will be 1:1 randomly assigned to the VA and DA groups. Once remission was achieved, consolidated chemotherapy will be performed and allogeneic hematopoietic stem cell transplantation is strongly recommended. After completion of the study intervention, participants will be followed-up every 1 to 2 months for up to 2 years.

This is an open-label, multicenter, phase 2b, randomized study aiming to compare the efficacy and safety of venetoclax plus azacytidine Versus daunorubicin plus cytarabine (conventional 7+3 regimen) in adult acute myeloid leukemia (AML) patients with adverse risk featuress. Newly diagnosed AML patients with adverse risk features according to 2022 European Leukemia Net risk stratification will be enrolled. In the study, a novel second generation targeted sequencing panel for the fast screening of adverse mutations with 72-hours after the bone marrow samples will be utilized. Randomized participants will receive induction treatment . Participants will be 1:1 randomly assigned to the VA and DA groups. VA regimen comprises of azacytidine, 75mg/m2, subcutaneously, on days 1-7; venetoclax, orally, once a day, 100mg, d1; 200mg, d2; 400mg, days 3-28. DA regimen comprises of daunorubicin (60mg/m2) on days 1-3, intraveneously injection, and cytarabine (100mg/m2) on days 1-7, intraveneously injection, for 1 cycle. Once remission was achieved, consolidated chemotherapy will be performed and allogeneic hematopoietic stem cell transplantation is strongly recommended. After completion of the study intervention, participants will be followed-up every 1 to 2 months for up to 2 years.

VA vs DA for Newly Diagnosed Hig-risk AML

Study of the Efficacy and Safety of Venetoclax Plus Azacytidine Versus Daunorubicin Plus Cytarabine in Adult Acute Myeloid Leukemia (AML) Patients With Adverse Risk Features

Rates of complete remission plus complete remission with incomplete blood cell rates of complete remission or complete remission with incomplete marrow recovery

Time between the first remission and relapse

time from the date of enrollment to treatment failure, relapse, death from any cause or the last follow-up

time from the date of enrollment to death from any cause or the last follow-up

The volume of infused blood products during the induction treatment.

Adverse events during the induction treatment.

complete remission or complete remission with incomplete marrow recovery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid Leukemia	NCT03850574	Relapsed or Ref...	Tuspetinib Venetoclax Oral...	18 Years -	Aptose Biosciences Inc.
Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid Leukemia	NCT03850574	Relapsed or Ref...	Tuspetinib Venetoclax Oral...	18 Years -	Aptose Biosciences Inc.
A Prospective Clinical Study of Bridging alloHSCT After Treatment With Obinutuzumab in Combination With Chidamide and Venetoclax in RR Ph-ALL and B-cell Lymphoma Patients	NCT06087419	Acute Lymphobla...	chidamide Venetoclax Oral... Inotuzumab Ozog...	18 Years -	Institute of Hematology & Blood Diseases Hospital, China
VA vs DA for Newly Diagnosed Hig-risk AML	NCT05939180	Acute Myeloid L...	Venetoclax Oral... Daunorubicin	18 Years - 64 Years	The First Affiliated Hospital of Soochow University
VA vs DA for Newly Diagnosed Hig-risk AML	NCT05939180	Acute Myeloid L...	Venetoclax Oral... Daunorubicin	18 Years - 64 Years	The First Affiliated Hospital of Soochow University

Spots Global Cancer Trial Database for venetoclax oral tablet