Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositivePhase 1/2NCT03576547
Venetoclax, Ponatinib, and Dexamethasone in Participants With Philadelphia Chromosome or BCR-ABL Positive Relapsed or Refractory Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia
A Phase 1/2 study testing Dexamethasone, Ponatinib Hydrochloride and Rituximab in people with Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Philadelphia Chromosome Positive, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I/II trial studies the best dose of venetoclax when given together with ponatinib and dexamethasone and to see how well they work in treating participants with Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukemia or chronic myelogenous leukemia that has come back or does not respond to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Philadelphia Chromosome Positive, Recurrent Acute Lymphoblastic Leukemia
- What is being tested?
- Dexamethasone, Ponatinib Hydrochloride and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jun 2018to 19 Jun 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with relapsed/refractory Ph-positive ALL or lymphoid blast phase CML (either t(9;22) and/or BCR-ABL1 positive by fluorescent in situ hybridization or polymerase chain reaction), including prior therapy with at least one Bcr-Abl tyrosine kinase inhibitor
- Performance status =< 3 Eastern Cooperative Oncology Group (ECOG scale)
- Total serum bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the principal investigator (PI)
- Alanine aminotransferase (ALT) =< 1.5 x ULN, unless due to the underlying leukemia approved by the PI
- Aspartate aminotransferase (AST) =< 1.5 x ULN unless due to the underlying leukemia approved by the PI
- Creatinine clearance >= 30 mL/min
Show all 9Show fewer
- Serum lipase and amylase =< 1.5 x ULN
- Ability to swallow
- Signed informed consent
Who cannot join
- Prior history of treatment with venetoclax. Prior ponatinib is allowed
- Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment)
- History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
- Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)
- Active secondary malignancy that in the investigator's opinion will shorten survival to less than 1 year
- Active grade III-V cardiac failure as defined by the New York Heart Association criteria
Show all 12Show fewer
- Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: any history of myocardial infarction (MI), stroke, revascularization, unstable angina or transient ischemic attack prior to enrollment; left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment; diagnosed or suspected congenital long QT syndrome; any history of clinically significant atrial or ventricular arrhythmias (such as uncontrolled atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) as determined by the treating physician; prolonged corrected QT interval (QTc) interval on pre-entry electrocardiogram (> 480 msec) unless corrected after electrolyte replacement; history of venous thromboembolism including deep venous thrombosis or pulmonary embolism within the past 3 months; uncontrolled hypertension (diastolic blood pressure > 100 mmHg; systolic > 150 mmHg)
- Patients currently taking drugs that are generally accepted to have a high risk of causing Torsades de Pointes (unless these can be changed to acceptable alternatives)
- Received strong or moderate CYP3A inhibitors or inducers within 3 days of study entry
- Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax
- Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator. Prior recent treatment with corticosteroids and hydroxyurea is permitted
- Pregnant and lactating women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception throughout the study period. Women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. Appropriate birth control will be determined by the treating physician
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Study of the Combination of Venetoclax, Ponatinib and Corticosteroids in Patients With Relapsed or Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia and Lymphoid Blast Phase Chronic Myelogenous Leukemia
This phase I/II trial studies the best dose of venetoclax when given together with ponatinib and dexamethasone and to see how well they work in treating participants with Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukemia or chronic myelogenous leukemia that has come back or does not respond to treatment. Drugs used in chemotherapy, such as venetoclax and dexamethasone, 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. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax, ponatinib, and dexamethasone may work better in treating participants with acute lymphoblastic leukemia or chronic myelogenous leukemia.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of venetoclax, ponatinib, and dexamethasone in patients with relapsed/refractory Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) or lymphoid blastic phase (BP)-chronic myelogenous leukemia (CML). (Phase I) II. To determine the efficacy of the regimen, as defined by the rate of complete remission (CR) or CR with incomplete count recovery (CRi). (Phase II)
SECONDARY OBJECTIVES:
- To determine efficacy outcomes, including rate of minimal residual disease negativity by polymerase chain reaction (PCR) for BCR-ABL1 transcripts, median relapse-free survival (RFS), and median overall survival (OS).
II. To determine the proportion of patients proceeding to allogeneic stem cell transplant (ASCT).
III. To preliminarily determine the safety of the combination regimen.
EXPLORATORY OBJECTIVES:
- To evaluate the effect of single-agent ponatinib on apoptotic proteins and Bcl-2 dependency.
II. To correlate apoptotic protein expression and Bcl-2 dependency on response and resistance to the combination regimen.
III. To assess impact of baseline genomics on outcomes with the combination regimen.
OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study.
INDUCTION (COURSE 1): Participants who have not received ponatinib within 2 weeks of the anticipated start date receive ponatinib orally (PO) daily on days 1-35, venetoclax PO daily on days 8-35, and dexamethasone PO or intravenously (IV) over 15 minutes on days 8-11. Participants who have received ponatinib within 2 weeks of the anticipated start date receive ponatinib PO and venetoclax PO daily on days 1-28 and dexamethasone PO or IV over 15 minutes on days 1-4. Participants with CD20 expression receive rituximab IV over 2-6 hours on days 14 and 21 at the discretion of the treating physician after the maximum dose of venetoclax has been reached.
CONSOLIDATION (COURSES 2-4): Participants receive ponatinib PO and venetoclax PO daily on days 1-28 and dexamethasone PO or IV over 15 minutes on days 1-4. Participants with CD20 expression receive rituximab IV over 2-6 hours for up to 2 doses each course at the discretion of the treating physician after the maximum dose of venetoclax has been reached. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE (COURSES 5+): Participants receive ponatinib PO and venetoclax PO daily on days 1-28 and dexamethasone PO or IV over 15 minutes on days 1-4. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Participants achieving remission undergo ASCT at the discretion of the treating physician.
After completion of study treatment, participants are followed up at 30 days.
- Conditions
- Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Philadelphia Chromosome Positive, Recurrent Acute Lymphoblastic Leukemia, Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Refractory Acute Lymphoblastic Leukemia, Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Being tested
- Dexamethasone, Ponatinib Hydrochloride, Rituximab, Venetoclax
- Medical subject headings
- Blast Crisis, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO or IV
Ponatinib HydrochlorideDrug
Also called AP24534 HCl, Iclusig
Given PO
RituximabBiological
Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody
Given IV
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Phase I (400 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab) | Experimental | The regimen consists of 4 cycles of induction/consolidation followed by up to 2 years of maintenance therapy for responding patients. Receives: Drug: Dexamethasone; Drug: Ponatinib Hydrochloride; Biological: Rituximab; Drug: Venetoclax |
| Phase I (800 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab) | Experimental | The regimen consists of 4 cycles of induction/consolidation followed by up to 2 years of maintenance therapy for responding patients. Receives: Drug: Dexamethasone; Drug: Ponatinib Hydrochloride; Biological: Rituximab; Drug: Venetoclax |
| Phase II Ponatinib MDT | Experimental | Participants in Phase II will receive the dose that was determined to be the Maximum Tolerated Dose (MDT) found in the Phase I portion of the study. The regimen consists of 4 cycles of induction/consolidation followed by up to 2 years of maintenance therapy for responding patients. Receives: Drug: Dexamethasone; Drug: Ponatinib Hydrochloride; Biological: Rituximab; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Venetoclax When Given in Combination With Ponatinib and Dexamethasone (Phase I)
MTD is defined as the highest dose level where a dose limiting toxicity (DLT) occurs within at most one out of six patients treated. The MTD is defined as the highest dose studied for which the observed incidence of DLT is less than 33%. Frequencies of toxicities will be tabulated according to the National Cancer Institute (NCI) Common Toxicity Criteria. Patients will be continued to be followed for one year for evidence of late toxicity.
Measured: Up to 1 year
Number of Participants With a Response Complete Response (CR) + CR With Incomplete Count Recovery (CRi)
Overall response rate, defined as the rate or complete response (CR) + CR with incomplete count recovery (CRi). Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10^9/L or above, and platelet count of 100 x 10^9/L. Complete resolution of all sites of extramedullary disease is required for CR. Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets < 100 x 10^9/L; neutrophils < 1 x 10^9/L).
Measured: 9 weeks
Event Free Survival (EFS)
Time from date of treatment start until the date of failure or death from any cause.
Measured: Monthly up to 5 years, 11 months and 7 days
Secondary outcomes (4)
Number of Participants Achieving Minimal Residual Disease Negativity
The proportion of patient achieving minimal residual disease negativity (as assessed by polymerase chain reaction PCR for BCR-ABL transcripts) after 2 cycles of therapy will be estimated.
Measured: After 2 cycles of therapy
Proportion of Patients Proceeding to Allogeneic Stem Cell Transplant (ASCT) a
All patients assessed for allogeneic stem cell transplant.
Measured: Up to 1 year
Overall Survival (OS)
Time from date of treatment start until date of death due to any cause or last Follow-up.
Measured: From treatment initiation to death or last follow-up, up to 5 years, 11 months and 7 days
Relapse-free Survival (RFS)
Relapse-free survival is the time from documented CR/CRi until relapse or death. Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10^9/L or above, and platelet count of 100 x 10^9/L. Complete resolution of all sites of extramedullary disease is required for CR. Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets < 100 x 10^9/L; neutrophils < 1 x 10^9/L).
Measured: Monthly up to 5 years, 11 months and 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2018
- Study start26 Jun 2018
- Primary completion19 Jun 2024
- Study completion19 Jun 2024
Why it stopped: The study was terminated early due to slow accrual and low level of interest both by the sponsor and by the department
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Farhad Ravandi-Kashani, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03576547
- Sponsor's protocol ID
- 2017-0313
- Other IDs
- NCI-2018-01100, 2017-0313
- Status last verified
- May 2025
- First submitted
- 26 Jun 2018
- Last updated
- 8 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of the Combination of Venetoclax, Ponatinib and Corticosteroids in Patients With Relapsed or Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia and Lymphoid Blast Phase Chronic Myelogenous Leukemia
- ClinicalTrials.gov ID
- NCT03576547
- Acronym / sponsor ID
- 2017-0313
- Conditions
- Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Philadelphia Chromosome Positive, Recurrent Acute Lymphoblastic Leukemia, Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Refractory Acute Lymphoblastic Leukemia, Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early due to slow accrual and low level of interest both by the sponsor and by the department
- Enrolment
- 9 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 26 Jun 2018 (actual)
- Primary completion
- 19 Jun 2024 (actual)
- Study completion
- 19 Jun 2024 (actual)
- First posted
- 3 Jul 2018 (actual)
- Results
- Posted 8 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I/II trial studies the best dose of venetoclax when given together with ponatinib and dexamethasone and to see how well they work in treating participants with Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukemia or chronic myelogenous leukemia that has come back or does not respond to treatment. Drugs used in chemotherapy, such as venetoclax and dexamethasone, 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. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax, ponatinib, and dexamethasone may work better in treating participants with acute lymphoblastic leukemia or chronic myelogenous leukemia.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of venetoclax, ponatinib, and dexamethasone in patients with relapsed/refractory Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) or lymphoid blastic phase (BP)-chronic myelogenous leukemia (CML). (Phase I) II. To determine the efficacy of the regimen, as defined by the rate of complete remission (CR) or CR with incomplete count recovery (CRi). (Phase II)
SECONDARY OBJECTIVES:
- To determine efficacy outcomes, including rate of minimal residual disease negativity by polymerase chain reaction (PCR) for BCR-ABL1 transcripts, median relapse-free survival (RFS), and median overall survival (OS).
II. To determine the proportion of patients proceeding to allogeneic stem cell transplant (ASCT).
III. To preliminarily determine the safety of the combination regimen.
EXPLORATORY OBJECTIVES:
- To evaluate the effect of single-agent ponatinib on apoptotic proteins and Bcl-2 dependency.
II. To correlate apoptotic protein expression and Bcl-2 dependency on response and resistance to the combination regimen.
III. To assess impact of baseline genomics on outcomes with the combination regimen.
OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study.
INDUCTION (COURSE 1): Participants who have not received ponatinib within 2 weeks of the anticipated start date receive ponatinib orally (PO) daily on days 1-35, venetoclax PO daily on days 8-35, and dexamethasone PO or intravenously (IV) over 15 minutes on days 8-11. Participants who have received ponatinib within 2 weeks of the anticipated start date receive ponatinib PO and venetoclax PO daily on days 1-28 and dexamethasone PO or IV over 15 minutes on days 1-4. Participants with CD20 expression receive rituximab IV over 2-6 hours on days 14 and 21 at the discretion of the treating physician after the maximum dose of venetoclax has been reached.
CONSOLIDATION (COURSES 2-4): Participants receive ponatinib PO and venetoclax PO daily on days 1-28 and dexamethasone PO or IV over 15 minutes on days 1-4. Participants with CD20 expression receive rituximab IV over 2-6 hours for up to 2 doses each course at the discretion of the treating physician after the maximum dose of venetoclax has been reached. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE (COURSES 5+): Participants receive ponatinib PO and venetoclax PO daily on days 1-28 and dexamethasone PO or IV over 15 minutes on days 1-4. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Participants achieving remission undergo ASCT at the discretion of the treating physician.
After completion of study treatment, participants are followed up at 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase I (400 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab) | Experimental | Drug: Dexamethasone, Drug: Ponatinib Hydrochloride, Biological: Rituximab, Drug: VenetoclaxThe regimen consists of 4 cycles of induction/consolidation followed by up to 2 years of maintenance therapy for responding patients. |
| Phase I (800 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab) | Experimental | Drug: Dexamethasone, Drug: Ponatinib Hydrochloride, Biological: Rituximab, Drug: VenetoclaxThe regimen consists of 4 cycles of induction/consolidation followed by up to 2 years of maintenance therapy for responding patients. |
| Phase II Ponatinib MDT | Experimental | Drug: Dexamethasone, Drug: Ponatinib Hydrochloride, Biological: Rituximab, Drug: VenetoclaxParticipants in Phase II will receive the dose that was determined to be the Maximum Tolerated Dose (MDT) found in the Phase I portion of the study. The regimen consists of 4 cycles of induction/consolidation followed by up to 2 years of maintenance therapy for responding patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with relapsed/refractory Ph-positive ALL or lymphoid blast phase CML (either t(9;22) and/or BCR-ABL1 positive by fluorescent in situ hybridization or polymerase chain reaction), including prior therapy with at least one Bcr-Abl tyrosine kinase inhibitor
- Performance status =< 3 Eastern Cooperative Oncology Group (ECOG scale)
- Total serum bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the principal investigator (PI)
- Alanine aminotransferase (ALT) =< 1.5 x ULN, unless due to the underlying leukemia approved by the PI
- Aspartate aminotransferase (AST) =< 1.5 x ULN unless due to the underlying leukemia approved by the PI
Key exclusion criteria (12 listed)
- Prior history of treatment with venetoclax. Prior ponatinib is allowed
- Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment)
- History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
- Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)
- Active secondary malignancy that in the investigator's opinion will shorten survival to less than 1 year
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO or IV | Drug | Phase I (400 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab), Phase I (800 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab), Phase II Ponatinib MDT |
| Ponatinib HydrochlorideAlso: AP24534 HCl, IclusigGiven PO | Drug | Phase I (400 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab), Phase I (800 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab), Phase II Ponatinib MDT |
| RituximabAlso: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 AntibodyGiven IV | Biological | Phase I (400 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab), Phase I (800 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab), Phase II Ponatinib MDT |
| VenetoclaxAlso: ABT-0199, ABT-199, ABT199, GDC-0199Given PO | Drug | Phase I (400 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab), Phase I (800 mg Ponatinib) Treatment (ponatinib, venetoclax, dexamethasone, rituximab), Phase II Ponatinib MDT |
Primary outcome
Maximum Tolerated Dose (MTD) of Venetoclax When Given in Combination With Ponatinib and Dexamethasone (Phase I)
Time frame: Up to 1 year
MTD is defined as the highest dose level where a dose limiting toxicity (DLT) occurs within at most one out of six patients treated. The MTD is defined as the highest dose studied for which the observed incidence of DLT is less than 33%. Frequencies of toxicities will be tabulated according to the National Cancer Institute (NCI) Common Toxicity Criteria. Patients will be continued to be followed for one year for evidence of late toxicity.
Number of Participants With a Response Complete Response (CR) + CR With Incomplete Count Recovery (CRi)
Time frame: 9 weeks
Overall response rate, defined as the rate or complete response (CR) + CR with incomplete count recovery (CRi). Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10^9/L or above, and platelet count of 100 x 10^9/L. Complete resolution of all sites of extramedullary disease is required for CR. Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets < 100 x 10^9/L; neutrophils < 1 x 10^9/L).
Event Free Survival (EFS)
Time frame: Monthly up to 5 years, 11 months and 7 days
Time from date of treatment start until the date of failure or death from any cause.
4 secondary outcomes
Number of Participants Achieving Minimal Residual Disease Negativity
Time frame: After 2 cycles of therapy
Proportion of Patients Proceeding to Allogeneic Stem Cell Transplant (ASCT) a
Time frame: Up to 1 year
Overall Survival (OS)
Time frame: From treatment initiation to death or last follow-up, up to 5 years, 11 months and 7 days
Relapse-free Survival (RFS)
Time frame: Monthly up to 5 years, 11 months and 7 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Farhad Ravandi-Kashani principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dexamethasone, Ponatinib Hydrochloride and Rituximab in people with Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Philadelphia Chromosome Positive, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of Venetoclax When Given in Combination With Ponatinib and Dexamethasone (Phase I) (time frame: Up to 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2025.