Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myeloid, Accelerated Phase

Blast Crisis

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Cell Transformation, Neoplastic

Carcinogenesis

Neoplastic Processes

Chronic Graft Versus Host Disease

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Acute Leukemia of Ambiguous Lineage

Lymphosarcoma

Chronic Myeloproliferative Disorders

All transplant recipients enrolled on this study in both the phase I and phase II portions will receive Orca-Q (Orca-Q Prime and Orca-Q Supplement) intravenously following myeloablative conditioning.

Orca-Q

Alexandra Mueller, MS

Beate Greer

Jordan Milner, MD

Priscilla Haakenson

Edward Ziga, MD, MPH

Damaris Rodriguez

Jorge Galvez Silva, MD

This is a first in children prospective study of allogeneic hematopoietic cell transplant using a centrally manufactured engineered donor graft (Orca-Q). The study will assess safety and efficacy of Orca-Q in pediatric patients with hematologic malignancies.

Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)

Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT) Recipients With Hematologic Malignancies (HM)

Evaluate primary graft failure through day +28, defined as being alive without recovery of neutrophils (achieving an absolute neutrophil count \>500/µL for 3 consecutive days) by day +28

Evaluate secondary graft failure through day +100, defined as neutrophil engraftment followed by subsequent decline in absolute neutrophil counts to \<500 µL, unresponsive to growth factor therapy and in the absence of alternative explanations such as recurrence of the underlying malignant disorder, infections, microangiopathy, medications causing bone marrow suppression or immune-mediated cytopenia.

Evaluate non-relapse mortality, defined as death without evidence of disease recurrence, at 12 months post-transplant

Evaluate non-relapse mortality, defined as death without evidence of disease recurrence, at 24 months post-transplant.

Determine the overall survival at 24 months post-transplant, as defined as the time from the date of transplant to the date of death from any cause or, for surviving patients, to the date of last follow-up.

Determine the relapse rate, as defined as the incidence of disease relapse through 12 months post-transplant. Disease relapse is defined as any of the following: ≥ 5% blasts in the bone marrow or peripheral blood, reappearance of pre-transplant cytogenetic abnormality, new evidence or redevelopment of extramedullary disease. Institution of any therapy to treat relapsed disease, such as withdrawal of immunosuppression or donor lymphocyte infusion (DLI), will be considered evidence of relapse regardless of whether any of these are met.

Determine the relapse rate, as defined as the incidence of disease relapse through 24 months post-transplant. Disease relapse is defined as any of the following: ≥ 5% blasts in the bone marrow or peripheral blood, reappearance of pre-transplant cytogenetic abnormality, new evidence or redevelopment of extramedullary disease. Institution of any therapy to treat relapsed disease, such as withdrawal of immunosuppression or donor lymphocyte infusion (DLI), will be considered evidence of relapse regardless of whether any of these are met.

Determine the rate of acute GVHD at 6 months post-transplant

Determine the rate of chronic GVHD through 24 months post-transplant.

Determine the rate of serious infections by 12 months post-transplant. A serious infection is defined as any new viral, bacterial, fungal or parasitic infection Common Terminology Criteria for Adverse Events v5.0 grade 2 or higher.

Describe treatment-emergent adverse events through 24 months post-transplant.

Evaluate the GVHD-free, relapse-free survival at 12 months post-transplant. GVHD-free, relapse-free survival is defined as freedom from grade III or IV acute GVHD, moderate or severe chronic GVHD, or disease progression or relapse.

Orca Biosystems, Inc.

Florida Department of Health

University of Florida

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Cytarabine

Daunorubicin

Nilotinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Nilotinib plus AD induction chemotherapy

* AD regimen : Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 7 days (D 1-7) plus Daunorubicin 90 mg/m2/day iv daily for 3 days (D 1-3)
* Nilotinib 400mg bid PO (continuous without interruption from D8 of induction chemotherapy)
* Re-induction chemotherapy AD regimen : Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 5 days (D 1-5) plus Daunorubicin 45 mg/m2/day iv daily for 2 days (D 1-2)

• Post-remission consolidation chemotherapy

* 4 courses of high-dose cytarabine will be given as post-remission therapy. Cytarabine 3 g/m2 will be administered in a 3-hour iv infusion every 12 hours on days 1, 3, and 5 (a total of six doses per course).
* Nilotinib 400mg bid PO will be administered continuously during consolidation chemotherapy and for 2 years after the consolidation therapy or until allogeneic hematopoietic stem cell transplantation

Nilotinib+AD induction

Hawk Kim, M.D., Ph.D.

Min Jung Kim, R.N.

Dong-Wook Kim, M.D., Ph.D.

Jae-Hoo Park, M.D., Ph.D.

Jae-Cheol Jo, M.D., Ph.D.

The current standard therapy in previously untreated adults with chronic phase (CP) of CML is imatinib and the result of long-term follow-up of IRIS study proves that imatinib for CML CP is reasonable therapy.(1, 2) However, some patients were initially diagnosed as advanced CML, accelerated phase (AP) or blastic phase (BP). Various chemotherapies were tried and were found that there were no highly effective chemotherapies for CML BP.(3-11) Imatinib in patients with these advanced CML is also disappointing because of low response rates as well as short response duration, and sudden transformation to BC is found even in initial CML CP patients. (12-17). Recent studies showed that nilotinib or dasatinib is better than imatinib in terms of rapid response and higher molecular response in newly diagnosed CML patients.(18-21) More potent bcr-abl suppression of nilotinib is supposed to be more active than imatinib even in patients with advanced CML. However, nilotinib in patients with imatinib-resistant or -intolerant CML BP showed low hematologic response and major cytogenetic response.(22, 23)

1. IMATINIB COMBINED WITH CHEMOTHERAPY FOR PHYLADELPHIA POSITIVE ACUTE LYMPHOBLASTIC LYMPHOMA (PH+ ALL) The trials combining imatinib with high-dose chemotherapy were successfully resulting in high response rate and longer survival and a role for bridging therapy to allogeneic hematopoietic stem cell transplantation (alloHSCT) by means of concurrent or alternating regimen in patients with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL).(24-29) Current combination therapy of imatinib and chemotherapy became standard therapy of Ph+ ALL and new 2nd generation TKIs are investigating. These experiences may be translated into the treatment of CML BP.
2. HIGH-DOSE DAUNORUBICIN IN ACUTE MYELOID LEUKEMIA (AML) INDUCTION CHEMOTHERAPY Two recently published papers of randomized trials comparing standard dose daunorubicin (45 mg/m2 for 3 days) and high dose daunorubicin (90 mg/m2 for 3 days) demonstrated improved CR rate and survival with high dose daunorubicin in younger (60 years or younger) and older (over 60 years) patients, respectively.(30, 31) Therefore high-dose daunorubicin can be applied safely and effectively to the treatment of CML BP.
3. NILOTINIB COMBINED WITH CHEMOTHERAPY FOR PHYLADELPHIA POSITIVE CML MYELOID BLASTIC PHASE (MBP) OR PHYLADELPHIA POSITIVE AML We will try 2nd generation TKI, nilotinib and high-dose daunorubicin induction chemotherapy combination to find out the combination therapy can improve response rate and survival in patients with CML MBP.

Nilotinib-Chemotherapy in CML Myeloid BP or Bcr-abl(+) AML

Nilotinib Combined by Chemotherapy for Myeloid Blastic Phase of Chronic Myeloid Leukemia or Bcr-abl Positive Acute Myeloid Leukemia

Primary purpose of this study is to define the efficacy of combined chemotherapy and nilotinib in chronic myeloid leukemia (CML) myeloid blastic phase (MBP) and bcr-abl positive acute myeloid leukemia (AML). The efficacy will be evaluated by complete remission (CR) rate.

* This study will also evaluate the safety of nilotinib and chemotherapy combination therapy.
* CTCAE ver. 4.03 will be used for safety measurement.

• This study will evaluate the impacts of nilotinib combined with chemotherapy on duration of CR, relapse-free survival (RFS), event-free survival (EFS), and overall survival (OS).

The Korean Society of Hematology CML working party

Ulsan University Hospital

Associate Professor

Decitabine

Antimetabolites

Based decitabine and olverembatinib（HQP1351)chemotherapy

AP-CML treated with decitabine 10mg/m2 d1-5 intravenously (IV) over 60 minutes on days 1-5 and HQP1351 40mg qod every 28 days.After completion of HQP1351 lead-in, patients will receive HQP1351 PO qod on days 1-28 of subsequent cycles.

BC-CML:treated with decitabine 20mg/m2 d1-5 IV on days 1-5 and HQP1351 40mg qod every 28 days,with or without other chemotherapy Drugs

based decitabine and olverembatinib（HQP1351)chemotherapy

Department of Hematology Nanfang Hospital Southern M University

This phase II trial studies how well the combination of based decitabine and olverembatinib（HQP1351)chemotherapy work for the treatment of blast phase or accelerated phase chronic myelogenous leukemia. Drugs used in chemotherapy such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. HQP1351 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine and ponatinib based chemotherapy may help to control blast phase or accelerated phase chronic myelogenous leukemia.

Accelerated Phase CML treated with decitabine10mg/m2 d1-5 intravenously (IV) over 60 minutes on days 1-5 and olverembatinib（HQP1351) 40mg qod every 28 days.After completion of HQP1351 lead-in, patients will receive HQP1351 PO daily on days 1-28 of subsequent cycles.

chronic myeloid leukaemia in blast phase:treated with decitabine 20mg/m2 d1-5 intravenously (IV) over 60 minutes on days 1-5 and HQP1351 40mg qod every 28 days,with or without other chemotherapy drugs

Decitabine and HQP1351-based Chemotherapy Regimen for the Treatment Advanced CML

Decitabine and HQP1351-based Chemotherapy Regimen for the Treatment Advanced Chronic Myeloid Leukemia

Defined as the proportion of patients achieving complete remission (CR) + CR with incomplete count recovery (CRi) occurring at the end of 2 cycles of treatment. Will be estimated along with the 95% credible interval. Patients who drop out of the study before completing 2 cycles and have been treated will be censored for the primary endpoint analysis.

From documented complete response until relapse or death

From first day of treatment until any failure (resistant disease, relapse, or death)

First day of treatment to time of death from any cause

Nanfang Hospital, Southern Medical University

professor

Annamaria Brioli, PhD MD

Christian Fabisch, Dr.

Jiri Mayer, Prof. Dr.

Christoph Röllig, PD Dr.

Joachim R. Göthert, Dr.

Georg-Nikolaus Franke, Dr.

Susanne Saussele, Prof. Dr.

Matthias Stelljes, Prof. Dr.

Elena Morozova, PhD Dr.

Iryna Dyagil, Dr.

Multicentric prospective and retrospective register collecting patient with CML blast crisis diagnosed in Germany and Europe

Since the advent of treatment with tyrosine kinase inhibitors (TKI), the incidence of blast crises has significantly decreased. Nevertheless, about 5% of patients diagnosed with chronic myeloid leukemia (CML) will evolve into a blast phase at some point during the course of their disease. Furthermore, despite the advances made in CML treatment, outcome of patients with blast crises are still dismal. Due to the rarity of this condition clinical trials are challenging, and collaboration between researchers both at national and international level is needed to collect a meaningful number of data.

European CML Blast Crisis Register

A joint publication is planned. But no data of trial Centers will be shared with the other trial centers.

how many patients survive after a blast crisis event

how many patients have a hematologic response to the local standard Treatment after a blast crisis event

how many patients have a molecular response to the local standard Treatment after a blast crisis event

how many patients have blast crisis events compared to all treated CML-patients in the trial centers

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)	NCT05322850	Acute Myeloid L... Acute Lymphoid ... Mixed Phenotype... Acute Undiffere... Chronic Myeloid... Chronic Myeloid... Chronic Myeloid...	Orca-Q	- 50 Years	University of Florida
Nilotinib-Chemotherapy in CML Myeloid BP or Bcr-abl(+) AML	NCT01690065	Chronic Myeloid... Untreated Adult...	Nilotinib+AD in...	18 Years - 65 Years	Ulsan University Hospital
Decitabine and HQP1351-based Chemotherapy Regimen for the Treatment Advanced CML	NCT05376852	Chronic Myeloid... Chronic Myeloid... Chronic Myeloid... Chronic Myeloid...	based decitabin...	14 Years -	Nanfang Hospital, Southern Medical University
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)	NCT05322850	Acute Myeloid L... Acute Lymphoid ... Mixed Phenotype... Acute Undiffere... Chronic Myeloid... Chronic Myeloid... Chronic Myeloid...	Orca-Q	- 50 Years	University of Florida
European CML Blast Crisis Register	NCT03869502	Chronic Myeloid...		18 Years -	University of Jena

Spots Global Cancer Trial Database for chronic myeloid leukemia in myeloid blast crisis