Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Philadelphia Chromosome

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Translocation, Genetic

Chromosome Aberrations

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Amino Acids

Etoposide

Cytarabine

Cyclophosphamide

Dexamethasone

Vincristine

Dexamethasone acetate

Etoposide phosphate

Dasatinib

Mercaptopurine

Vindesine

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Dasatinib, QD p.o. administration, day 1 to EOS

Dasatinib p.o. + Chemotherapy (Dexamethasone, Cyclophosphamide, Vincristine, Methotroxate, 6-Mercapto-Purine, Cytarabine, Vindesine, VP16 (Etoposide))

Nicola Gökbuget, Dr.med

The current standard treatment approach for young patients with Positive Acute Lymphoblastic Leukemia (Ph+ALL) is the combination of a chemotherapy protocol employing four to five cytotoxic agents typically used for ALL together with imatinib. It is recommended to propose allogeneic Standard Induction and Consolidation Therapy (SCT) to all eligible patients with a suitable donor and to continue imatinib with or without additional therapy in patients not undergoing SCT.

This protocol is a study for newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia in patients aged 18 to 55 years.

The objective of this strategy is to improve the overall results in the treatment of adult ALL with the addition of specific molecules to the common chemotherapeutic schedule.

In the present study, the potent ABL tyrosine kinase inhibitor, Dasatinib will be added to standard induction and consolidation chemotherapy for the Philadelphia positive chromosome sub-group of ALL patients aged 18 to 55 years.

The Study hypothesis is, that Dasatinib in combination with standard chemotherapy according to GMALL protocol 07/2003 is feasible and induces cytologic and molecular remission rates comparable to chemotherapy in combination with imatinib without increased treatment-related mortality.

Study of Frontline Dasatinib Plus Chemotherapy in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (PH+ALL)

Open Label Phase II Study to Evaluate the Safety of Standard Induction and Consolidation Therapy in Combination With Dasatinib in Newly Diagnosed Adult Patients With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (PH+ALL)

Goethe University

Hematopoietic Stem Cell Transplantation in Acute Leukemia Ph positive

Hematopoietic Stem Cell Transplantation

Renato Fanin, Professor

This study includes a registry-based, nationwide analysis to describe the clinical outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a Tyrosine Kinase Inhibitors (TKI)-based treatment.

This was a retrospective nationwide analysis based on registry data collected by GITMO. Inclusion criteria were: 1) diagnosis of Ph+ ALL; age ≥18 years at transplant; 2) patients receiving first allogeneic HSCT from any donor (HLA-identical sibling donor (MSD), unrelated donor (UD) or alternative donor (haploidentical or cord blood) between 2005 and 2016 in a GITMO center; 3) TKI-based treatment prior to HSCT; 4) patients with available pre-transplant MRD status, as well as complete clinical data and outcome. Data were extracted from the GITMO Registry (PROMISE Registry).

The endpoints of the study were: OS, progression-free survival (PFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), cumulative incidence of extensive chronic graft versus host disease (cGVHD), rate of minimal residual disease (MRD) negativity and the rate of complete cytologic remission (CR) before and after transplant.

SCT in Ph Positive Acute Lymphoblastic Leukemia

Outcome of Hematopoietic Stem Cell Transplantation in Philadelphia Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors. A Registry-based Study of the Italian Blood and Marrow Transplantation Society (GITMO)

Data were extracted from the GITMO Registry (PROMISE Registry). All patients included in the registry signed an informed consent form. The study was conducted in compliance with current national and European legislation on clinical trials, in accordance with the Helsinki Declaration and the principles of good clinical practice (GCP). This study was approved by the GITMO board and by the institutional review board of the coordinating center (Hematology-University of Udine) and from institutional review boards of all participating centers.

Gruppo Italiano Trapianto di Midollo Osseo

CANDONI ANNA

Principal Investigator, Clinical Professor

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Blast Crisis

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Cell Transformation, Neoplastic

Carcinogenesis

Neoplastic Processes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Methotrexate

Idarubicin

Imatinib Mesylate

BB 1101

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Tubulin Modulators

Antimitotic Agents

Antiviral Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Folinic Acid

Folate

Vitamin B9

imatinib

vincristine

cyclophosphamide

cytosine arabinoside

dexamethasone

idarubicin

methotrexate (intrathecal)

AraC (intrathecal)

dexamethasone (intrathecal)

Oliver G Ottmann, M.D.

Barbara Wassmann, M.D.

The aims of the study are to determine whether single agent imatinib (STI571; Glivec) is more effective as up-front remission induction therapy than conventional multi-agent induction chemotherapy for elderly patients with Philadelphia positive (Ph+)ALL, whether this treatment is better tolerated, and whether subsequent combination therapy with imatinib and chemotherapy of approximately a 1 year duration is tolerable and effective with respect to maintaining remissions.

Study Comparing Imatinib With Chemotherapy as Induction in Elderly Patients With Philadelphia Positive Acute Lymphoblastic Leukemia (ALL)

A Randomized, Multicenter Open Label Phase II Study to Determine the Safety and Efficacy of Induction Therapy With Imatinib in Comparison With Standard Induction Chemotherapy in Elderly (> 55 Years) Patients With Ph Positive Acute Lymphoblastic Leukemia (ALL)

Johann Wolfgang Goethe University Hospital

Blinatumomab

Ascentage Pharma HQP1351 bioavailable inhibitor

Administered in all patients as a continuous IV infusion at the dosage of 28μg daily (9μg daily for Cycle 1 Day 1 to Day 7).

Bill Garrett

Sarah Weaver

Omer Jamy, MD

London Hall

Thad Beck, MD

Paul Koller, MD

Shannon Gleason

Anthony Hunter, MD

Amelia Barkman

Maria Baer, MD

Erik Lewerenz

Sudipto Mukherjee, MD

Jovitta Jacob

Elias Jabbour, MD

Kaysey Orlowski

Vivian Oehler, MD

Yifan Zhai, MD, PhD

A multi-center, open-label, randomized, phase Ib study to evaluate the pharmacokinetics (PK) of HQP1351 and to determine the recommended phase 2 dose (RP2D) of HQP1351 in subjects with CML chronic phase (CP), accelerated phase (AP), or blast phase (BP) or with Ph+ ALL, who have experienced resistance or intolerance to at least two tyrosine kinase inhibitors (TKIs) or in subjects with Ph+ B-cell precursor (BCP) ALL or lymphoid blast phase CML (CML LBP), who have experienced resistance or intolerance to at least one second or later generation TKI.

Approximately 40 patients will be randomized at 3:3:2 ratio into one of three HQP1351 monotherapy dose cohorts (Cohort A, B, and C): 30 mg every other day (QOD), 40 mg QOD, and 50 mg QOD, with 15, 15, and 10 patients in Cohort A, B, and C. The first cycle of 28 days is considered as the dose-limiting toxicity (DLT) observation period. If the incidence of DLTs exceeds 20% (2 patients) in 50 mg dose cohort during the first cycle of therapy, this dose cohort will be stopped. The randomization will be stratified to 4 groups: T315I mutated CML-CP and CML-AP, T315I un-mutated CML-CP, T315I unmutated CML-AP, and CML-BP and Ph+ ALL to ensure that the subgroups are represented across all dose cohorts. Blood samples will be collected from each subject at specified time points to evaluate the PK of HQP1351. RP2D of HQP1351 will be determined based on the comprehensive analyses of the PK, safety, and efficacy data of the US patients treated with HQP1351, when compared with that in the Chinese patients.

Eligible patients will have disease resistance to or intolerance to at least two TKIs, for patients with T315I mutation, number of pretreated TKIs is not restricted. Patients will be administered HQP1351 orally QOD during a period of 28 days (1 cycle).

Cohort D (HQP1351 + blinatumomab) will enroll patients with relapsed/refractory Ph+ BCP ALL or CML-BP using a dose escalation and expansion design. Patients will be administered HQP1351 orally QOD at an assigned dose with blinatumomab at repeated 42-day cycles. The first cycle of 42 days is considered as the DLT observation period. The initial dose of HQP1351 will be 30 mg QOD.

A total of 40 patients will be randomized at 3:3:2 ratio into one of the three dose cohorts (Cohorts A, B, and C): 30 mg every other day (QOD), 40 mg QOD and 50 mg QOD, with 15, 15, and 10 patients in Cohort A, B, and C.

For Cohort D: 14 to 22 Ph+ BCP ALL or CML LBP patients will be enrolled.

Study of HQP1351 in Subjects With Refractory CML and Ph+ ALL

A Phase Ib Study of the Pharmacokinetics, Safety and Efficacy of Orally Administered HQP1351 in Subjects With Refractory Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)

To evaluate the Maximum Plasma Concentration (Cmax) of HQP1351

To evaluate the Area Under the Curve (AUC) of HQP1351

Ascentage Pharma Group Inc.

Leukemia, Myeloid, Chronic-Phase

Leukemia, Myeloid, Accelerated Phase

Nilotinib

Janus Kinase Inhibitors

Nilotinib: Given that recommended dose of Nilotinib for imatinib failed CML patients is 400mg twice daily, Nilotinib dose will remain fixed at 400mg bid throughout the cycles.

Ruxolitinib: In the phase I part of the study, dose escalation will follow a 3+3 study design. Dose modifications will not occur, as the purpose of this study is to determine the maximum tolerated dose. Ruxolitinib will be given at one of 3 fixed dose levels for the duration of their treatment, either 10mg twice daily, 15mg twice daily or 20mg twice daily.

Nilotinib dose will remain fixed at 400mg bid throughout the cycles. BCR-ABL kinase inhibitor

In the phase I part of the study, dose escalation will follow a 3+3 study design at either of 3 fixed dose levels (10 mg bid, 15 mg bid or 20 mg bid).

No intra-patient dose-escalation will occur. JAK inhibitor

Ruxolitinib

Dennis Kim, MD/PhD

This is the study to test combination regimen of Nilotinib and Ruxolitinib therapy for the treatment of patients with Philadelphia positive chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL) who is resistant to multiple tyrosine kinase inhibitor therapies with BCR-ABL kinase inhibition activity. Ruxolitinib is a tyrosine kinase inhibitor blocking alternative pathway independent of BCR-ABL mediated pathway, thus having a potential to overcome tyrosine kinase inhibitor resistance in Philadelphia positive CML or ALL patients. Phase I study will be conducted to define a recommended phase II dose (RPTD) and phase II study will examine the hypothesis that combinational approach will increase response rate of resistant CML/ALL patients, thus evaluating efficacy of the combination regimen.

The purpose of this study is to find out if multiple tyrosine kinase inhibitor resistant chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL) can be treated with combination approach of Nilotinib with Ruxolitinib which may block alternative pathway besides BCR-ABL kinase inhibition in Ph positive leukemia, esp against JAK2-STAT5 pathway. First step is to define the dose of Ruxolitinib with fixed dose of Nilotinib which had been approved at the dose of 400mg bid for imatinib failed CML.

During phase I part of the study,dose escalations will be decided on the basis of DLTs observed hence the exact sample size could not be predicted with certainty but will range between 9-12 patients. Three patients will be enrolled per dose level. Accordingly 9 patients are expected to be enrolled. If a DLT is observed, 3 more patients will be enrolled at the dose level in which the DLT occurred.

The study will be conducted at multiple sites across Canada and enrollment will be competitive. Once 3 patients are enrolled in a cohort, that dose level will be closed to enrollment until safety assessment of the 3 subjects is performed at the end of cycle 1. This procedure will be performed for each dosing cohort. Patients will be assigned to a dose level based on authorization from the sponsor in collaboration with Ozmosis Research Inc.

For the phase II part of the study, once the RPTD has been established in the phase I portion of this trial, the phase II will begin. The phase II portion will be a two-stage, single arm, unblinded study investigating the potential efficacy of the combination of Ruxolitinib and Nilotinib.

A maximum of 20 patients will be accrued in the phase II portion. Those patients treated in the phase I portion of this trial at the RPTD will be included in the analysis of the Phase II study.

Phase I/II Study of Nilotinib/Ruxolitinb Therapy for TKI Resistant Ph-Leukemia

A PHASE I/II, MULTI-CENTRE, TRIAL OF RUXOLITINIB THERAPY IN COMBINATION WITH NILOTINIB IN PATIENTS WITH PHILADELPHIA POSITIVE CHRONIC MYELOID LEUKEMIA OR ACUTE LYMPHOBLASTIC LEUKEMIA WHO HAVE FAILED TYROSINE KINASE INHIBITOR THERAPY

Cmax will be measured for the maximum plasma concentration of nilotinib after oral administration.

Maximum Tolerated Dose (MTD) of Ruxolitinib with fixed dose of Nilotinib. Dose escalation will follow a 3+3 study design. The CTCAE v4.03 criteria will be used. Grade 4 toxicity will be accounted as dose limiting toxicity (DLT).

Major cytogenetic response defined by 35% or less of Philadelphia chromosomes by metaphase cytogenetics in marrow from CML and ALL patients

Complete hematologic response defined by CBC differential without any evidence of leukemia. It will be evaluated in CML patients in AP or BP, and patients with Ph+ ALL.

Major cytogenetic response defined by 35% or less of Philadelphia chromosomes by metaphase cytogenetics in marrow taken at 6 months.

It will be defined by NCI Common Terminology Criteria for Adverse Events (CTCAE)version 4.03 for adverse event reporting.

Complete hematologic response defined by CBC differential without any evidence of leukemia. It will be evaluated in the CML patients in AP or BP and in patients with Ph+ ALL.

Novartis

University Health Network, Toronto

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Frontline Dasatinib Plus Chemotherapy in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (PH+ALL)	NCT01724879	Philadelphia Po...	Dasatinib	18 Years - 55 Years	Goethe University
SCT in Ph Positive Acute Lymphoblastic Leukemia	NCT03821727	Philadelphia Po... SCT	Hematopoietic S...	18 Years -	University Hospital, Udine, Italy
Study Comparing Imatinib With Chemotherapy as Induction in Elderly Patients With Philadelphia Positive Acute Lymphoblastic Leukemia (ALL)	NCT00199186	Philadelphia Po... Lymphoid Blasti...	imatinib vincristine cyclophosphamid... cytosine arabin... dexamethasone idarubicin methotrexate (i... AraC (intrathec... dexamethasone (...	56 Years -	Johann Wolfgang Goethe University Hospital
Study of HQP1351 in Subjects With Refractory CML and Ph+ ALL	NCT04260022	Leukemia, Myelo... Myeloid Leukemi... Chronic Myeloid... Philadelphia Po... B Cell Precurso...	Ascentage Pharm... Blinatumomab	18 Years -	Ascentage Pharma Group Inc.
Phase I/II Study of Nilotinib/Ruxolitinb Therapy for TKI Resistant Ph-Leukemia	NCT01914484	Chronic Phase C... Accelerated Pha... Blastic Phase C... Philadelphia Po... Resistant to Ty...	Nilotinib Ruxolitinib	18 Years -	University Health Network, Toronto
Study of HQP1351 in Subjects With Refractory CML and Ph+ ALL	NCT04260022	Leukemia, Myelo... Myeloid Leukemi... Chronic Myeloid... Philadelphia Po... B Cell Precurso...	Ascentage Pharm... Blinatumomab	18 Years -	Ascentage Pharma Group Inc.
Study Comparing Imatinib With Chemotherapy as Induction in Elderly Patients With Philadelphia Positive Acute Lymphoblastic Leukemia (ALL)	NCT00199186	Philadelphia Po... Lymphoid Blasti...	imatinib vincristine cyclophosphamid... cytosine arabin... dexamethasone idarubicin methotrexate (i... AraC (intrathec... dexamethasone (...	56 Years -	Johann Wolfgang Goethe University Hospital

Spots Global Cancer Trial Database for philadelphia positive acute lymphoblastic leukemia