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Low-Intensity Chemotherapy, Ponatinib and Blinatumomab in Treating Patients With Philadelphia Chromosome-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT03147612
Recruitment Status : Recruiting
First Posted : May 10, 2017
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies how well low-intensity chemotherapy and ponatinib work in treating patients with Philadelphia chromosome-positive and/or BCR-ABL positive acute lymphoblastic leukemia that may have come back or is not responding to treatment. Drugs used in chemotherapy, such as cyclophosphamide, vincristine, dexamethasone, methotrexate, and cytarabine, 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. Immunotherapy with rituximab and blinatumomab, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Granulocyte colony stimulating factor helps the bone marrow make recover after treatment. Giving low-intensity chemotherapy, ponatinib, and blinatumomab may work better in treating patients with acute lymphoblastic leukemia.

Condition or disease Intervention/treatment Phase
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Acute Lymphoblastic Leukemia Acute Myeloid Leukemia With BCR-ABL1 Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Philadelphia Chromosome Positive Recurrent Acute Lymphoblastic Leukemia Refractory Acute Lymphoblastic Leukemia Biological: Blinatumomab Drug: Cyclophosphamide Drug: Cytarabine Biological: Filgrastim Drug: Methotrexate Biological: Pegfilgrastim Drug: Ponatinib Biological: Rituximab Drug: Vincristine Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of the Sequential Combination of Low-Intensity Chemotherapy and Ponatinib Followed by Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome (Ph)-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)
Actual Study Start Date : February 8, 2018
Estimated Primary Completion Date : February 8, 2024
Estimated Study Completion Date : February 8, 2024


Arm Intervention/treatment
Experimental: Treatment (chemotherapy, ponatinib, blinatumomab)
See Detailed Description.
Biological: Blinatumomab
Given via central catheter
Other Names:
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • Blincyto
  • MEDI-538
  • MT-103

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Drug: Cytarabine
Given intrathecally or IV
Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453

Biological: Filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim

Drug: Methotrexate
Given intrathecally or IV
Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039

Biological: Pegfilgrastim
Given SC
Other Names:
  • Filgrastim SD-01
  • filgrastim-SD/01
  • Fulphila
  • HSP-130
  • Jinyouli
  • Neulasta
  • Neulastim
  • Pegfilgrastim Biosimilar HSP-130
  • Pegfilgrastim Biosimilar Pegcyte
  • SD-01
  • SD-01 sustained duration G-CSF

Drug: Ponatinib
Given PO
Other Names:
  • AP-24534
  • AP24534

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
  • rituximab biosimilar TQB2303
  • rituximab-abbs
  • RTXM83
  • Truxima

Drug: Vincristine
Given IV
Other Names:
  • LEUROCRISTINE
  • VCR
  • Vincrystine




Primary Outcome Measures :
  1. Complete molecular response (CMR) in newly diagnosed Philadelphia chromosome (Ph)-positive and/or BCR-ABL-positive participants [ Time Frame: Up to 84 days (3 courses) ]
    The CMR rate within the first 3 courses for cohort 1 or rate within the first 2 courses for cohort 2 will be estimated along with the 95% credible intervals. Similar analyses will be performed for estimating the rate of complete cytogenetic response and major molecular response rates.

  2. Overall response (OR) in participants with relapsed/refractory acute lymphoblastic leukemia [ Time Frame: Up to 6 years ]
    Overall response is defined as complete response (CR) + complete response with hematologic improvement (CRi) in participants with relapsed/refractory disease.


Secondary Outcome Measures :
  1. Complete cytogenetic response [ Time Frame: Up to 6 years ]
    Will be estimated along with the 95% credible intervals.

  2. CMR for relapsed/refractory population [ Time Frame: Up to 6 years ]
    Will be estimated along with the 95% credible intervals.

  3. Event-free survival (EFS) [ Time Frame: From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 6 years ]
    The Kaplan-Meier method will be used to assess EFS probabilities for each cohort.

  4. Overall survival (OS) [ Time Frame: From the first day of treatment to time of death from any cause, assessed up to 6 years ]
    The Kaplan-Meier method will be used to assess OS probabilities for each cohort.

  5. Incidence of adverse events (AEs) [ Time Frame: Up to 6 years ]
    Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0. The proportion of patients with AEs will be estimated, along with the Bayesian 95% credible interval.



Information from the National Library of Medicine

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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 >= 18 years of age with previously untreated Ph-positive ALL (either t(9;22) and/or BCR-ABL positive) (includes patients initiated on first cycle of hyper-CVAD before cytogenetics known. These patients could have received one or two cycles of chemotherapy with or without other TKIs and still eligible. If they achieved CR, they are assessable only for event-free and overall survival, or If they failed to achieve CR, they are assessable for CR, event-free, and overall survival or 3) Patients >= 18 years of age with relapsed/refractory Ph-positive ALL or lymphoid accelerated or blast phase chronic myelogenous leukemia (CML)
  • Performance status =< 2 (Eastern Cooperative Oncology Group [ECOG] scale)
  • Total serum bilirubin =< 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome
  • Alanine aminotransferase (ALT) =< 3 x ULN
  • Aspartate aminotransferase (AST) =< 3 x ULN
  • Serum lipase and amylase =< 1.5 x ULN
  • Creatinine =< 2.0 mg/dl
  • Female patients who: are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR if they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
  • Adequate cardiac function as assessed clinically by history and physical examination
  • Signed informed consent

Exclusion Criteria:

  • Active serious infection not controlled by oral or intravenous antibiotics
  • Known active hepatitis B. Patients with chronic hepatitis B who are on appropriate viral suppressive therapy may be allowed after discussion with the principal investigator (PI)
  • History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
  • History of alcohol abuse
  • Uncontrolled hypertriglyceridemia (triglycerides > 450mg/dL)
  • Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma) 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
  • Uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: myocardial infarction (MI), stroke, or revascularization within 3 months; unstable angina or transient ischemic attack; congestive heart failure prior to enrollment, or 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; clinically significant atrial or ventricular arrhythmias as determined by the treating physician; prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 470 msec) unless corrected after electrolyte replacement. or approved by cardiologist; Significant venous or arterial thromboembolism including deep venous thrombosis or pulmonary embolism. Patients with a history of treated prior superficial or catheter associated phlebitis will not be considered as significant embolism and after discussion with principal investigator (PI) will not be excluded from eligibility. Uncontrolled hypertension (diastolic blood pressure > 90 mmHg; systolic > 140mmHg). Patients with hypertension should be under treatment on study entry to effect blood pressure control
  • Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days or 5 half-lives before the first dose of ponatinib in patients with newly diagnosed only
  • History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. Patients with active CNS leukemia will NOT be excluded
  • Current autoimmune disease or history of autoimmune disease with potential CNS involvement
  • 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
  • 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. 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
  • History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand's disease); and diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  • Patients with documented significant pleural or pericardial effusions unless they are thought to be secondary to their leukemia

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): NCT03147612


Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Elias Jabbour    713-792-4764      
Principal Investigator: Elias Jabbour         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Elias Jabbour M.D. Anderson Cancer Center

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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03147612     History of Changes
Other Study ID Numbers: 2016-0402
NCI-2018-01186 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0402 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: May 10, 2017    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: August 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
Leukemia, Myeloid, Accelerated Phase
Blast Crisis
Philadelphia Chromosome
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
Cytarabine
Cyclophosphamide
Rituximab
Methotrexate
Vincristine
Blinatumomab
Ponatinib