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Venetoclax, Ponatinib, and Dexamethasone in Participants With Philadelphia Chromosome or BCR-ABL Positive Relapsed or Refractory Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia

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ClinicalTrials.gov Identifier: NCT03576547
Recruitment Status : Recruiting
First Posted : July 3, 2018
Last Update Posted : May 20, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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 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.

Condition or disease Intervention/treatment Phase
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 t(9;22) Drug: Dexamethasone Drug: Ponatinib Hydrochloride Biological: Rituximab Drug: Venetoclax Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 26, 2018
Estimated Primary Completion Date : January 31, 2020
Estimated Study Completion Date : January 31, 2020


Arm Intervention/treatment
Experimental: Treatment (ponatinib, venetoclax, dexamethasone, rituximab)
See Detailed Description
Drug: Dexamethasone
Given PO or IV
Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • Visumetazone

Drug: Ponatinib Hydrochloride
Given PO
Other Names:
  • AP24534 HCl
  • Iclusig

Biological: Rituximab
Given IV
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83

Drug: Venetoclax
Given PO
Other Names:
  • ABT-0199
  • ABT-199
  • ABT199
  • GDC-0199
  • RG7601
  • Venclexta




Primary Outcome Measures :
  1. 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.

  2. Overall response rate [ Time Frame: 9 weeks ]
    Overall response rate, defined as the rate or complete response (CR) + CR with incomplete count recovery (CRi)


Secondary Outcome Measures :
  1. Rate of minimal residual disease negativity assessed by polymerase chain reaction (PCR) for BCR-ABL transcripts [ Time Frame: 9 weeks ]
  2. Proportion of patients proceeding to allogeneic stem cell transplant (ASCT) a [ Time Frame: Up to 1 year ]
  3. Overall survival (OS) [ Time Frame: From treatment initiation to death or last follow-up, assessed up to 1 year ]
    Kaplan-Meier curves will be used to estimate unadjusted OS distribution.

  4. Relapse-free survival (RFS) [ Time Frame: Up to 1 year ]
    Kaplan-Meier curves will be used to estimate unadjusted RFS distribution.

  5. Incidence of adverse events evaluated according to NCI Common Toxicity Criteria [ Time Frame: Up to 1 year ]
    Toxicity type, severity, and attribution will be summarized for each patient using frequency tables.

  6. Median time to allogeneic stem cell transplant (ASCT) [ Time Frame: Up to 1 year ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Serum lipase and amylase =< 1.5 x ULN
  • Ability to swallow
  • Signed informed consent

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03576547


Contacts
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Contact: Farhad Ravandi-Kashani 713-745-0394 fravandi@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Farhad Ravandi-Kashani    713-745-0394      
Principal Investigator: Farhad Ravandi-Kashani         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Farhad Ravandi-Kashani M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03576547     History of Changes
Other Study ID Numbers: 2017-0313
NCI-2018-01100 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0313 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: July 3, 2018    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Blast Crisis
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes
Dexamethasone
Dexamethasone acetate
Rituximab
Venetoclax
Ponatinib
BB 1101
Antibodies
Immunoglobulins