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| Name | Class |
|---|---|
| Novartis | INDUSTRY |
| Queen Mary Hospital, Hong Kong | OTHER |
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The goal of this clinical trial is to learn if Asciminib, a first in class allosteric inhibitor, as a add-on maintenance therapy can provides benefits and further prevents relapse in post allogenic hematopoietic stem-cell transplant (HSCT) of patients with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL) or blastic transformed Chronic Myeloid Leukemia (CML-BP).
The main questions it aims to answer are:
Would Ascminib add-on maintenance therapyimprove Morphological relapse-free survival rate? Would Ascminib add-on maintenance therapy improve Molecular relapse-free survival and Overall survival ? Any toxicity or intolerable events during Ascminib add-on maintenance therapy?
Researchers will compare Study arm (Ascminib plus tyrosine-kinase inhibitors [TKIs]) and Control arm (TKIs only) to see if Ascminib add-on maintenance therapy would provide better relapse-free survival (RFS) with optimal tolerability.
Participants will
Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL) or blastic transformed Chronic Myeloid Leukemia (myeloid or lymphoid) (CML-BP) represent a group of high-risk disease. The outcome has improved since the introduction of tyrosine kinase inhibitors (TKIs). However, a significant proportion of patients still relapse despite undergoing allogeneic (allo-) hematopoietic stem cell transplant (HSCT) and post-transplant maintenance with TKIs. Moreover, many patients may not be able to tolerate the standard recommended dose of TKIs due to cytopenia especially during the early phase after transplant.
Asciminib is a first in class allosteric inhibitor that works by a mechanism totally different from the current TKIs in market. Its safety and efficacy have been studied in previous studies. We therefore postulate that combination of standard ATP-competitive TKIs (our current standard of care) and asciminib as post allo-HSCT maintenance can more effectively reduce risk of relapse post-transplant without increased toxicities.
This is a two-arm, parallel group, single-center, prospective, open-label, randomized clinical study to investigate the efficacy and safety of adding asciminib to the standard-of-care for post allogenic HSCT maintenance in patients with Ph+ B-ALL or CML-BP to prevent post-HSCT relapse.
Subjects in study group will receive Asciminib plus standard of care (SOC) while those in control group will receive standard of care. Eligible subjects will be randomized into study group and control group in a 2:1 ratio.
The subjects in study group commence study drug (Asciminib) for post-transplant maintenance at 80 mg QD (in combination with nilotinib or dasatinib) or 60 mg QD (in combination with imatinib) after stable count recovery (i.e. absolute neutrophile count [ANC] ≥ 1.0 × 109/L, granulocyte colony-stimulating factor (G-CSF) independent and platelet ≥ 50 × 109/L, transfusion independent). SOC TKI will be added from 5th week onwards after.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study Arm (ASC + TKIs) | Experimental | Asciminib (ASC) add-on with a 2 years treatment on ONE of the following tyrosine kinase inhibitors (TKIs): Imatinib / Dasatinib / Nilotinib. TKI will be added from 5th week onwards after. |
|
| Control Arm (TKIs only) | Other | 2-years treatment on ONE of the following tyrosine kinase inhibitors (TKIs): Imatinib / Dasatinib / Nilotinib |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Asciminib add-on | Drug | Asciminib 80mg QD (in combination with Nilotinib or Dasatinib) or Asciminib 60mg QD (in combination with Imatinib) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Morphological relapse-free survival (M-RFS) | Morphological relapse-free survival (M-RFS) is defined as the time from date of allogeneic Hematopoietic Stem Cell Transplantation (HSCT) until the date of first documented morphological relapse or death from any cause, whichever occurs earlier. Morphological relapse is defined as the presence of ≥ 5% blasts in the bone marrow and/or evidence of new onset extramedullary disease. | From date of allogeneic HSCT until the date of first documented morphological relapse or death from any cause, whichever occurs earlier, up to 12 years. |
| Measure | Description | Time Frame |
|---|---|---|
| Molecular relapse-free survival (m-RFS) | Molecular RFS is defined as the time from the date of randomization to the date of documented molecular relapse or the date of death from any causes, whichever occurs earlier. Molecular relapse was defined as loss of major molecular response (MMR, defined as BCR::ABL1 transcript ≤0.1% on the international scale for p210 transcript and/or a 3-log reduction from baseline for p190 transcript). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Garret M.K. LEUNG, MBBS, MRCP(UK), FHKCP(HK) | Contact | +852 2255 3975 | lmk381@ha.org.hk | |
| Joycelyn P.Y. SIM, MBBS, MRCP(UK), FHKCP(HK) | Contact | +852 2255 3975 | simpyj@ha.org.hk |
| Name | Affiliation | Role |
|---|---|---|
| Yok-Lam KWONG, MBBS, MD, FRCP(UK), FRCPath(UK | The University of Hong Kong & Queen Mary Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Hong Kong | Hong Kong | Hong Kong |
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This is a two-arm, parallel group, single-center, prospective, open-label, randomized clinical study to investigate the efficacy and safety of adding asciminib to the standard-of-care for post allogenic hematopoietic stem-cell transplant (HSCT) maintenance in patients with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL) or blastic transformed Chronic Myeloid Leukemia (myeloid or lymphoid) (CML-BP) to prevent post-HSCT relapse. Ph+ B-ALL and CML-BP patients will not be stratified.
Subjects in study group will receive Asciminib plus standard of care (SOC) while those in control group will receive SOC. Eligible subjects will be randomized into study group and control group in a 2:1 ratio.
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| Imatinib | Drug | Imatinib 300mg QD (Ramp-up from 100mg QD for first 4-weeks, 200mg QD for following 4-weeks then 300mg QD for subsequent weeks), Maximum 2-years treatment |
|
| Dasatinib | Drug | Dasatinib 50mg QD (Ramp-up from 20mg QD for first 4-weeks, 40mg QD for following 4-weeks then 50mg QD for subsequent weeks), Maximum 2-years treatment |
|
| Nilotinib | Drug | Nilotinib 200mg BID (Ramp-up from 200mg QD for first 4-weeks then 200mg BID for subsequent weeks), Maximum 2-years treatment |
|
| From date of randomization until the date of first documented molecular relapse or death from any cause, whichever occurs earlier, up to 12 years. |
| Cumulative incidence of grade II-IV acute Graft versus Host Disease (acute GvHD) | Cumulative incidence of grade II-IV acute GvHD (by Mount Sinai Acute GvHD International Consortium [MAGIC] criteria) | Within 100 day after allogeneic Hematopoietic Stem Cell Transplantation (HSCT) |
| Cumulative incidence of chronic Graft versus Host Disease (chronic GvHD) | Cumulative incidence of moderate to severe chronic GvHD (by National Institute of Health [NIH] criteria) requiring systemic treatment | From enrollment through study completion, an average of 2 years |
| Treatment toxicities and Adverse Events (AEs) | Number of incidence of Treatment toxicities and adverse events will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 throughout the study duration, from baseline through 24 months post-treatment or end of study participation. | From randomization through treatment completion, an average of 2 years |
| Event-free survival (EFS) | Event-free survival (EFS) is defined as the time from the date of Hematopoietic Stem Cell Transplantation (HSCT) to the date of morphological disease relapse, molecular relapse, onset of acute or chronic GvHD, or death from any cause. | From date of allogeneic HSCT until the date of first documented morphological relapse, molecular relapse, onset of acute of chronic GvHD or death from any cause, whichever occurs earlier, up to 12 years. |
| Overall survival (OS) | Overall survival (OS) is defined as the time from the date of Hematopoietic Stem Cell Transplantation (HSCT) to the time of death. | From date of allogeneic HSCT until the date of death from any cause or trial completion, whichever occurs earlier, up to 12 years. |
| 2-year morphological relapse-free survival rate (2-year M-RFS rate) | The proportion of subjects with morphological relapse-free survival at 2 years from time of Hematopoietic Stem Cell Transplantation (HSCT). | From date of allogeneic HSCT until the date of first documented morphological relapse, molecular relapse, or death from any cause, whichever occurs earlier, up to 2 years. |
| ID | Term |
|---|---|
| D000068877 | Imatinib Mesylate |
| D000069439 | Dasatinib |
| C498826 | nilotinib |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D001393 | Azoles |
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