Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Lymphosarcoma

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Nilotinib

Dasatinib

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

1 year to \< 10 years pediatric patients with newly diagnosed CP-Ph+ CML, or CP or AP-Ph+ CML resistant/intolerant to imatinib and/or dasatinib, or relapsed/refractory Ph+ ALL (acute lymphoblastic leukemia) treated at the proposed dose of 230 mg/m2 bid.

\>= 10 years to \<18 years pediatric patients with newly diagnosed CP-Ph+ CML, or CP or AP-Ph+ CML resistant/intolerant to imatinib and/or dasatinib, or relapsed/refractory Ph+ ALL (acute lymphoblastic leukemia) treated at the proposed dose of 230 mg/m2 bid.

Nilotinib capsules were delivered in bottles with dose strengths of 50mg, 150mg and 200mg.

Patients were administered nilotinib 230 mg/m2 (per BSA) bid, orally, rounded to the nearest 50 mg (max single dose 400 mg) for 28 days (1 cycle) for up to 12 cycles prior to protocol amendment 3 and up to 24 cycles post amendment 3. Capsules were to be swallowed whole with water. Apple sauce (puréed apple) may have been used as a vehicle for dosing where capsules were not able to be swallowed whole with water.

Novartis Pharmaceuticals

This study will assess the pharmacokinetics of nilotinib in Ph+ CML pediatric patients that are newly diagnosed or resistant or intolerant to imatinib or dasatinib or refractory or relapsed Ph+ ALL compared to the adult populations. It will also evaluate safety and activity of nilotinib as secondary objectives.

A Pharmacokinetic (PK) Study of Nilotinib in Pediatric Patients With Philadelphia Chromosome-positive (Ph+) Chronic Myelogenous Leukemia (CML) or Acute Lymphoblastic Leukemia (ALL)

A Multi-center, Open-label, Pharmacokinetic Study of Oral Nilotinib in Pediatric Patients With Newly Diagnosed Chronic Phase (CP) Ph+ CML, With CP or Accelerated Phase (AP) Ph+ CML Resistant/Intolerant to Imatinib and/or Dasatinib, or With Refractory/Relapsed Ph+ ALL

The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

The steady-state PK profiles of nilotinib in pediatric patients were estimated using trough sampling following multiple 230 mg/m2 bid doses

The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose.

A confirmed complete hematological response (CHR) is defined when all of the following criteria are achieved at two consecutive assessments, at least 4 weeks apart: white blood cell (WBC) count \< 10 × 109/L; platelet \< 450 × 109/L; basophils \< 5%; no blasts and promyelocytes in peripheral blood (PB); myelocytes + metamyelocytes \< 5% in PB; and no extramedullary involvement. The information used for hematological assessment was to be obtained from the laboratory and extramedullary data, all merged by patient and date.

Cytogenetic response was initially assessed as the percentage of Ph+ metaphases in the bone marrow (BM) and performed within 21 days prior to study entry. A major cytogenetic response (0% to 35% Ph+ metaphases test positive for the Philadelphia chromosome) combines both complete cytogenetic (CCyR) and partial cytogenetic response (PCyR). CCyR implies 0% Ph+ metaphases in the BM, PCyR is \> 0% to 35%, minor cytogenetic response (mCyR) is \> 35% to 65%, minimal response is \> 65% to 95% and no response is \> 95% Ph+ metaphases in the BM.

The bcr-abl gene fusion encodes for a BCR-ABL fusion protein. Depending on the precise location of the fusion, the molecular weight of this protein can range from 185 to 210 kDa. Consequently BCR-ABL is referred to as p185 or p210 transcript. For the patients expressing the major BCR-ABL transcript p210, molecular response was defined and reported as the percent ratio of BCR-ABL transcripts/control gene transcripts converted to a reference standard according to the International Scale (IS). A major molecular response (MMR) is defined as a BCR-ABL/control gene ratio ≤ 0.1% (equal to a 3 log reduction in BCR-ABL transcripts) on the IS. In this study, the control gene was abl.

Best Response in Ph+ ALL patients was defined as either Complete Remission (CR) with platelet recovery, Complete Remission (CR) with incomplete platelet recovery, Partial Remission (PR) or Stable disease. Stable disease was defined is defined as failure to qualify for either CR, PR, or progressive disease.

Group 1

\>= 10 years to \<18 years pediatric patients

Group 2

Total

Age, Continuous

Sex: Female, Male

Weight

Height

Body Mass Index (BMI)

Full analysis set (FAS): consists of all patients who passed the screening and are enrolled into the study. Patients may or may not have taken study drug.

Study Director

Pharmacokinetic Analysis Set (PAS) consists of all patients who received the nilotinib dose on Day 1, had an evaluable Day 1 PK profile or provided at least one evaluable steady state trough concentration.

Summary of Nilotinib Non-compartmental PK Parameters: Cmax

Number of Ph+ CML Participants With Confirmed Complete Hematologic Response (CHR)

Summary of Nilotinib Non-compartmental PK Parameters: Tmax

Summary of Nilotinib Non-compartmental PK Parameters: AUClast (Last = 24h)

Summary of Nilotinib Non-compartmental PK Parameters: AUC0-12h

Summary of Nilotinib Steady-state PK Parameters: AUCss

Summary of Nilotinib Steady-state PK Parameters: CLF (Body Surface Area (BSA) Adjusted)

Summary of Nilotinib Steady-state PK Parameters: Cmin

Complete cytogenic response (CCyR)

Partial cytogenic response (PCyR)

Minor cytogenic response (mCyR)

Minimal

None

Absence of Ph+ at baseline

FAS consist of all patients (pts) who passed screening \& are enrolled into study. Patients may or may not have taken study drug. One (1) Ph+ CML patient in Group 2 was Ph+ at baseline \& discontinued study prior to subsequent cytogenetic assessment. This pt doesn't appear in any cytogenic response category.

Number of Ph+ CML Participants With Cytogenic Response

Number of Ph+ CML Participants With Major Molecular Response (MMR)

Complete Remission with platelet recovery

Complete Remission w/incomplete platelet recovery

Partial remission

Stable disease

Progressive disease

Efficacy Endpoints for Ph+ ALL Patients

Overall Study

Neoplasm, Residual

Neoplastic Processes

Anti-Infective Agents

Inotuzumab Ozogamicin

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Immunotoxins

Immunoconjugates

Immunologic Factors

patients enrolled treated with the combination of Olverembatinib and Inotuzumab to clear the persistent MRD.

patients in this arm will accept a 28 days treatment regimen: Olverembatinib 40mg QOD (d1 to d28 )and Inotuzumab Ozogamicin 1.2mg/m2 (divided into 2 days, d1 and d8, 0.6mg/m2, respectively).

the usage of Olverembatinib combined with Inotuzumab Ozogamicin

Hematopoietic stem cell transplantation (HSCT) is the effective and even the only cure treatment option for ph+ acute lymphocyte leukemia (ph+ALL). However, the outcome has been insufficient and relapse remains the major cause of treatment failure and poor survival, especially for patients with persistent minimal residual disease (MRD). It is believed that clearance of MRD pre-HSCT could significantly reduce the incidence of relapse post-HSCT. Olverembatinib has been documented as a promising third generation of TKIs. Meanwhile, Inotuzumab ozogamicin (InO) , an antibody-drug conjugate approved in the US and the European Union, has been applied in relapsed/refractory acute lymphoblastic leukemia (R/R ALL) and achieved good treatment outcome. This prospective, single arm and multicenter study is to investigate the efficacy and safety of combination of Olverembatinib and Ino for MRD clearance before bridging to HSCT.

A Study of Olverembatinib Combined With Inotuzumab Ozogamicin in the Treatment ph+ ALL With MRD Persistent Positive

A Prospective, Single-arm, Multi-center Study of Olverembatinib Combined With Inotuzumab Ozogamicin in the Treatment ph+ ALL With MRD Persistent Positive

The ratio of patients achieved MRD remission. The MRD remission was defined as the fusion gene BCR-ABL quantification in bone marrow samples was lower than the detection limit of RT-PCR ( \< 0.01 %, the residual number of leukemia cells detected in our hospital was 0.0032 % ) ; at the same time, flow cytometry ( FACS ) was used to monitor the MRD of the cells, and the proportion of abnormal cells \< 0.1 % was MRD-

For patients achived MRD remission, HSCT will be performed. The one year overall survival after HSCT will be the seconday outcom.

For patients achived MRD remission, HSCT will be performed. The one year relaspe free survival after HSCT will be the seconday outcom.

For patients achived MRD remission, HSCT will be performed. The one year non-relaspe mortality after HSCT will be the seconday outcom.

Institute of Hematology & Blood Diseases Hospital, China

Translocation, Genetic

Chromosome Aberrations

Ponatinib

Michael Beck, PhD

This prospective registry is initiated to follow up on the use of Iclusig® in patients with CML or Ph+ ALL in routine practice in Belgium.

Iclusig® (Ponatinib) in Clinical Practice for the Treatment of Chronic Myeloid Leukemia or Ph+ Acute Lymphoblastic Leukemia in Belgium

Prospective Registry of Iclusig® (Ponatinib) Used in Clinical Practice for the Treatment of Patients With Chronic Myeloid Leukemia or Ph+ Acute Lymphoblastic Leukemia in Belgium

Prescribed dose of Iclusig® in milligrams.

Includes treatment effectiveness, complete hematologic response, cytogenetic response, major molecular response.

Costs associated with the treatment of Iclusig®-related adverse events reported during the registry.

Incyte Biosciences Benelux

ponatinib plus reduced-intensity chemotherapy in first-line treatment of Adult Ph+ ALL

Ponatinib 15 MG Oral Tablet

Cyril Salek, MD

This is a phase II interventional trial to evaluate the efficacy of ponatinib plus reduced-intensity chemotherapy in the first-line treatment of adult patients with Ph+ acute lymphoblastic leukemia. This combination has the potential to improve the depth of molecular responses after the induction phase of treatment. Patients who achieve a complete molecular response (CMR) at week 11 will not be directed to alloSCT and will receive consolidation chemotherapy combined with ponatinib, followed by 24 months of ponatinib maintenance. The aim is to spare individuals with a low probability of relapse from overtreatment with more intensive and toxic transplant procedure.

Primary Objective:

To evaluate the percentage of complete molecular responses (CMR) after two cycles of remission induction therapy composed of two cycles of chemotherapy plus ponatinib. CMR is defined as BCR-ABL1 below the Limit of Quantification by Droplet Digital Polymerase Chain Reaction (ddPCR).

Outline:

Pre-phase:

dexamethasone 10 mg/m2 PO (day -5 till -1), cyclophosphamide IV 200 mg/m2 (day -3 till -1), methotrexate 15 mg IT.

Induction I:

ponatinib 30 mg/day PO once daily (QD) continuously since day 1, rituximab 375 mg/m2 IV (day 1), dexamethasone 10 mg/m2 PO (day 1-2, 8-11), vincristine 2 mg IV (day 1, 8, 15), Granulocyte-Colony Stimulating Factor (G-CSF) until recovery.

Induction II:

ponatinib 30 mg/day PO QD continuously, rituximab 375 mg/m2 IV (day 23), cyclophosphamide 1000 mg/m2 IV (day 24), cytarabine 75 mg/m2 IV (day 26-29, 33-36), Granulocyte StimuG-CSF until recovery, methotrexate 15 mg IT (day 26, 33) methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 40). Week 11: Primary endpoint assessment.

Consolidation I (week 12):

ponatinib 30 mg/day PO QD continuously, rituximab 375 mg/m2 IV (day 1), dexamethasone 10 mg/m2 PO (day 1-4), vindesine 3 mg/m2 IV (day 2), methotrexate 1.5 g/m2 IV (day 2), cytarabine 2x 2 g/m2 IV (day 5), G-CSF until recovery, methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 8). Patients in complete molecular response at week 11 will be treated with 5 additional blocks of chemotherapy followed by maintenance therapy; patients with molecular failure at week 11 will end the study and be directed to alloSCT.

Consolidation II (week 18):

ponatinib 15 mg/day PO QD continuously, rituximab 375 mg/m2 IV (day 1), cyclophosphamide 500 mg/m2 IV (day 2,3), etoposide (VP-16) 75 mg/m2 IV (day 2,3), methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 1).

Consolidation III+V (weeks 24 and 36):

ponatinib 15 mg/day PO QD continuously, rituximab 375 mg/m2 IV (day 1), methotrexate 1.5 g/m2 IV (day 2), vincristine 1 mg IV (day 2), 6-mercaptopurine 60 mg/m2 PO (day 2-8), methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT at day 1.

Consolidation IV+VI (weeks 30+40):

ponatinib 15 mg/day PO QD continuously, rituximab 375 mg/m2 IV (day 1), dexamethasone 10 mg/m2 PO (day 1-4), cytarabine 1.5 g/m2 IV (day 1+3+5), methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 1). Maintenance: ponatinib 15 mg/day PO QD continuously 24 months. (Doses of IV methotrexate and cytarabine are reduced in patients \>55 years.)

Ponatinib Plus Reduced-intensity Chemotherapy in the First-line Treatment of Adult Patients With Ph+ ALL

Ponatinib Plus Reduced-intensity Chemotherapy in the First-line Treatment of Adult Patients With Ph-positive Acute Lymphoblastic Leukemia

Percentage of patients with Complete Molecular Response (CMR) after 2 cycles of induction therapy composed by reduced chemotherapy and ponatinib. Minimal Residual Disease (MRD) tested by quantification of BCR-ABL1 transcript using ddPCR method

Complete Remission (CR) and Complete Remission with incomplete blood count recovery(CRi)

Percentage of patients with suboptimal molecular response after completion of 2 induction course containing ponatinib

Severity and occurence of adverse events related to ponatinib treatment

CZECRIN - Czech Clinical Research Infrastructure Network

Institute of Hematology and Blood Transfusion, Czech Republic

XL228

The purpose of this study is to determine the safest dose of the BCR-ABL inhibitor XL228, how often it should be taken, and how well people with leukemia tolerate XL228.

Study of XL228 in Subjects With Chronic Myeloid Leukemia or Philadelphia-Chromosome-Positive Acute Lymphocytic Leukemia

A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL228 Administered Intravenously to Subjects With Chronic Myeloid Leukemia (CML) or Philadelphia-Chromosome-Positive Acute Lymphocytic Leukemia (Ph+ ALL)

Exelixis

Asciminib

Dose escalation study estimated the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of asciminib in adult patients with chronic myeloid leukemia (CML).

Dose escalation study estimated the MTD and/or RDE of asciminib in combination with Nilotinib in adult CML patients

Dose escalation study estimated the MTD and/or RDE of asciminib in adult patients with Ph positive ALL patients

Dose escalation study to estimate the MTD and/or RDE of asciminib in combination with imatinib in adult CML patients

Dose escalation study estimated the MTD and/or RDE of asciminib in combination with dasatinib in adult CML patients

Asciminib was be administered orally in a dose escalation schedule.

Asciminib (ABL001)

Asciminib and Nilotinib was administered orally in CML patients

Asciminib and imatinib was administered orally in CML patients

Imatinib

Asciminib and dasatinib was administered orally in CML patients

The design of a phase I, open label, dose finding study was chosen in order to establish a safe and tolerated dose of single agent ABL001 in Chronic myeloid leukemia (CML) and Philadelphia chromosome positive Acute lymphoblastic leukemia (Ph+ ALL) patients who are relapsed or refractory to or are intolerant of Tyrosine kinase inhibitors (TKIs), and of ABL001+Nilotinib, ABL001+Imatinib and ABL001+Dasatinib in Ph positive CML patients who are relapsed or refractory to TKIs.

This first-in-human trial with ABL001 was a dose escalation study whose primary purpose was to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of single agent ABL001 in CML or Ph+ ALL patients, and in combination with either Nilotinib or Imatinib or Dasatinib in Ph positive CML patients. The safety, tolerability and pharmacokinetic (PK) profile of ABL001 and ABL001+Nilotinib, ABL001+Imatinib and ABL001+Dasatinib were assessed together with an evaluation of pharmacodynamic (PD) changes in peripheral blood mononuclear cells (PBMC) and bone marrow aspirates and all data could contribute to the assessment of the RDE.

An understanding of the MTD/RDE, safety profile, PK/PD relationship, and preliminary evidence of anti-CML and ALL activity wias used to inform future development in adults with CML and Ph+ ALL. By virtue of its distinct pharmacological profile and by preclinical pharmacological studies demonstrating an additive effect, a combination of ABL001 and a tyrosine-kinase inhibitor (TKI) has the potential to achieve a deeper molecular response in a higher proportion of CML patients as compared to single agent TKI therapy. Such a combination has the added advantage of targeting the ABL kinase domain at two distinct locations, theoretically preventing single point mutation-associated treatment resistance. The prediction is that a nilotinib+ABL001, imatinib+ABL001 and/or dasatinib+ABL001 combination will increase the percentage of patients who achieve a complete molecular response (CMR) and decrease the time to CMR, thereby increasing the possibility of achieving sustained treatment-free remissions in these patients. In addition, some patients could be intolerant of therapy with TKIs or could develop mutations that promote resistance to TKI therapy. In these patients, ABL001 could provide a novel therapeutic option.

A Phase I Study of Oral Asciminib (ABL001) in Patients With CML or Ph+ ALL

A Phase I, Multicenter, Open-label Study of Oral ABL001 in Patients With Chronic Myelogenous Leukemia (CML) or Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Determine the MTD and/or RDE of ABL001 as single agent in CML and Ph+ ALL, and in combination with either nilotinib or imatinib or dasatinib in CML patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Pharmacokinetic (PK) Study of Nilotinib in Pediatric Patients With Philadelphia Chromosome-positive (Ph+) Chronic Myelogenous Leukemia (CML) or Acute Lymphoblastic Leukemia (ALL)	NCT01077544	Chronic Myeloid... Acute Lymphobla...	Nilotinib	1 Year - 17 Years	Novartis
A Study of Olverembatinib Combined With Inotuzumab Ozogamicin in the Treatment ph+ ALL With MRD Persistent Positive	NCT05603156	Ph+ ALL Bone Marrow Tra... Minimal Residua...	the usage of Ol...	18 Years -	Institute of Hematology & Blood Diseases Hospital, China
Iclusig® (Ponatinib) in Clinical Practice for the Treatment of Chronic Myeloid Leukemia or Ph+ Acute Lymphoblastic Leukemia in Belgium	NCT03678454	Chronic Myeloid... CML Philadelphia Ch... Ph+ ALL		18 Years -	Incyte Corporation
Ponatinib Plus Reduced-intensity Chemotherapy in the First-line Treatment of Adult Patients With Ph+ ALL	NCT04554459	Acute Lymphobla... Ph+ ALL Newly Diagnosed	Ponatinib 15 MG...	18 Years - 99 Years	Institute of Hematology and Blood Transfusion, Czech Republic
Ponatinib Plus Reduced-intensity Chemotherapy in the First-line Treatment of Adult Patients With Ph+ ALL	NCT04554459	Acute Lymphobla... Ph+ ALL Newly Diagnosed	Ponatinib 15 MG...	18 Years - 99 Years	Institute of Hematology and Blood Transfusion, Czech Republic
Study of XL228 in Subjects With Chronic Myeloid Leukemia or Philadelphia-Chromosome-Positive Acute Lymphocytic Leukemia	NCT00464113	Chronic Myeloid... Leukemia, Lymph...	XL228	18 Years -	Exelixis
A Pharmacokinetic (PK) Study of Nilotinib in Pediatric Patients With Philadelphia Chromosome-positive (Ph+) Chronic Myelogenous Leukemia (CML) or Acute Lymphoblastic Leukemia (ALL)	NCT01077544	Chronic Myeloid... Acute Lymphobla...	Nilotinib	1 Year - 17 Years	Novartis
Study of XL228 in Subjects With Chronic Myeloid Leukemia or Philadelphia-Chromosome-Positive Acute Lymphocytic Leukemia	NCT00464113	Chronic Myeloid... Leukemia, Lymph...	XL228	18 Years -	Exelixis
A Phase I Study of Oral Asciminib (ABL001) in Patients With CML or Ph+ ALL	NCT02081378	Chronic Myeloge... Philadelphia Ch...	Asciminib (ABL0... Nilotinib Imatinib Dasatinib	18 Years -	Novartis
Iclusig® (Ponatinib) in Clinical Practice for the Treatment of Chronic Myeloid Leukemia or Ph+ Acute Lymphoblastic Leukemia in Belgium	NCT03678454	Chronic Myeloid... CML Philadelphia Ch... Ph+ ALL		18 Years -	Incyte Corporation

Spots Global Cancer Trial Database for ph+ all

Every month we try and update this database with for ph+ all cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ph+ all

Every month we try and update this database with for ph+ all cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ph+ all cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.