- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04845035
Pediatric-Inspired Chemotherapy Plus Tyrosine Kinase Inhibitor in Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
A Phase II Study Using a BFM Regimen Plus Tyrosine Kinase Inhibitor in Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
This study will combine a standard, pediatric-inspired, chemotherapy regimen with the tyrosine kinase inhibitors (TKIs) Dasatinib and Ponatinib to treat adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.
There are two age groups/cohorts:
- participants aged 18 to 59 years
- participants aged 60 years and older
One tyrosine kinase inhibitor (TKI), either Dasatinib or Ponatinib, will be administered in each of the respective chemotherapy cycles. The TKI (either Dasatinib or Ponatinib) administered in a given cycle of chemotherapy will be dictated by the given cycle's standard chemotherapy, in order to minimize overlapping side effects of the chemotherapy and TKI.
The dosages of the standard chemotherapy agents, as well as the tyrosine kinase inhibitors (TKIs)--Dasatinib and Ponatinib--have been adjusted for each age group to allow continuous administration of these TKIs.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109
- University of Michigan Rogel Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Key Inclusion Criteria
- Patients ≥ 18 years of age.
- Baseline ECOG Performance Status ≤ 2, and patient is a candidate for intensive chemotherapy.
- Newly diagnosed Ph+ ALL.
- Written informed consent prior to any screening procedures. Permitted exceptions are that the diagnostic marrow exam/peripheral blood/nodal biopsy tests confirming Ph+ B-Cell ALL, as well as pre-induction cardiac workup (EKG/TTE/MUGA), may be performed prior to the patient providing written informed consent if these tests are within 14 days of enrollment.
- Patient able to give informed consent.
B-cell Acute Lymphoblastic Leukemia with BCR-ABL1, i.e., Philadelphia chromosome-positive (Ph+) ALL.
- B-Cell lineage determined by standard flow cytometry/IHC
- Ph+ by cytogenetics (karyotype/FISH) and/or molecular (BCR-ABL1 transcripts)
- Determined in CLIA-certified laboratory
Previously untreated, except for below allowances in a recent diagnosis and up until 48 hours after starting trial therapy:
- Corticosteroids
- Hydroxyurea
- Leukapheresis
Key Exclusion Criteria
Any of the following subtypes of ALL:
- Ph-negative B-Cell ALL.
- T-Cell ALL.
- Relapsed Ph+ ALL.
- Lymphoid blast crisis of chronic myeloid leukemia (CML).
- Mature B-Cell (Burkitt's) ALL.
- Clinical signs of CNS disease.
- Active ALL in CNS or testes.
- Estimated Glomerular Filtration Rate (eGFR) by MDRD formula and calculated creatinine clearance (CrCl), based on a 24-hour urine collection, < 30 mL/min-unless related to ALL/tumor lysis syndrome and able to be corrected.
- Total Bilirubin > 2x ULN; AST/ALT > 10x ULN, unless related to ALL liver infiltration.
- Patients with known history of HIV, Hepatitis B, or Hepatitis C.
- Pre-treatment QTcF > 480 msecs.
- Left Ventricular Ejection Fraction < 45%. If an initial TTE demonstrates LVEF < 45%, a confirmatory MUGA should be performed to confirm LVEF is < 45% prior to excluding the patient. Both a TTE and a MUGA with LVEF < 45% are needed to exclude a patient. Either a TTE or MUGA alone, if LVEF is ≥ 45%, is sufficient to include a patient.
Have significant or active cardiovascular disease, specifically including but not restricted to:
- Known prior type 1 (thrombotic) myocardial infarction (type 2 myocardial infarction/demand ischemia is not necessarily excluded).
- History of clinically significant atrial arrhythmia or any ventricular arrhythmia.
- Unstable angina within the last 12 months.
- Congestive heart failure within the last 12 months.
- Currently uncontrolled hypertension (≥ Grade 3; or systolic blood pressure ≥ 160 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg).
- Acute pancreatitis within the last year or a history of chronic pancreatitis.
- Have malabsorption syndrome or other gastrointestinal illness that could affect the absorption of orally administered chemotherapy.
- Ongoing uncontrolled severe nausea or vomiting.
History of a significant bleeding disorder unrelated to ALL, including:
- Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease).
- Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
- Taking any medications or herbal supplements that are known to be strong inhibitors or inducers of CYP3A4 within at least 7 days or 5 half-lives (whichever is longer) before the first dose of study chemotherapy on day 1 of Remission Induction Phase I (RIP1).
- Active malignancy requiring treatment, other than ALL, within two years prior to start of treatment, with the exception of basal cell or squamous cell carcinoma of the skin, colon polyp, carcinoma in situ of the cervix, or DCIS or LCIS of the breast.
- Active uncontrolled infection, any other concurrent disease, or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator.
- Pregnant women or women who are breast-feeding
- Men and women of childbearing potential must be willing to practice an effective method of birth control during treatment and up until 30 days following the end of trial therapy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BFM + Tyrosine Kinase Inhibitor
This study has 2 cohorts: participants aged 18 - 59 years and participants aged 60 or more years.
Both cohorts receive the same study intervention with dosage adjusted for age.
Participants receive the Berlin-Frankfurt-Münster (BFM) protocol plus dasatinib during a two-phase induction and a delayed re-induction.
Participants receive the BFM protocol plus ponatinib during post-induction consolidations and maintenance.
|
By mouth
By mouth
with varied cycles, including Daunorubicin, Vincristine, Prednisone, Pegaspargase, Rituximab, Cytarabine, Mercaptopurine, Cyclophosphamide, Methotrexate, Doxorubicin, Thioguanine, and Dexamethasone
Intrathecal
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of complete molecular remission (CMR) at the end of one cycle of Dasatinib + BFM
Time Frame: Post day 36; up to day 43
|
CMR will be assessed by minimal residual disease (MRD)-negative status, using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) analysis from bone marrow aspirates, after 1 cycle of induction therapy with Berlin-Frankfurt-Münster (BFM) protocol and Dasatinib.
|
Post day 36; up to day 43
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Adverse Events related to Dasatinib and Ponatinib
Time Frame: 30 days after last treatment, up to approximately 3 years
|
Per NCI CTCAE v5.0 toxicity data, specifically:
|
30 days after last treatment, up to approximately 3 years
|
Percentage of participants who begin ponatinib post-induction that complete at least one cycle.
Time Frame: At 18 weeks
|
Feasibility will be assessed by the percentage, among patients who begin the ponatinib post-induction regimen, that complete at least one cycle.
Completion is defined as the ability to tolerate ≥ 80% dose intensity of all prescribed anti-cancer agents per cycle of ponatinib initiated.
|
At 18 weeks
|
Complete hematologic (morphologic) remission (CHR) rate after induction
Time Frame: After Remission Induction Phase I and at end of study treatment, up to approximately 3 years
|
Bone marrow assessed by morphologic review of both the aspirate smear and core biopsy
|
After Remission Induction Phase I and at end of study treatment, up to approximately 3 years
|
Complete cytogenic remission (CCyR) rate post induction
Time Frame: After Remission Induction Phase I and at end of study treatment, up to approximately 3 years
|
Bone marrow aspirate assessed by karyotype and/or fluorescence in situ hybridization (FISH).
|
After Remission Induction Phase I and at end of study treatment, up to approximately 3 years
|
Complete molecular remission (CMR) rate
Time Frame: After Remission Induction Phase I and at end of study treatment, up to approximately 3 years
|
Bone marrow aspirate analyzed by RT-qPCR.
|
After Remission Induction Phase I and at end of study treatment, up to approximately 3 years
|
Disease-free survival (DFS)
Time Frame: up to five years after end of study treatment (approximately 8 years)
|
Disease-Free Survival (DFS) is defined as the duration of time from attainment of CR (morphologic remission, hematologic remission, etc) to Morphologic Relapse (Relapsed Disease) or Death.
|
up to five years after end of study treatment (approximately 8 years)
|
Overall survival (OS).
Time Frame: up to five years after end of study treatment (approximately 8 years)
|
Overall Survival (OS) is defined as the length of time from the date of diagnosis that patients diagnosed with the disease are still alive.
|
up to five years after end of study treatment (approximately 8 years)
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Patrick Burke, MD, University of Michigan
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Chromosome Aberrations
- Translocation, Genetic
- Leukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Philadelphia Chromosome
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Protein Kinase Inhibitors
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Cytarabine
- Methotrexate
- Ponatinib
- Dasatinib
Other Study ID Numbers
- UMCC 2018.144
- HUM00171952 (Other Identifier: University of Michigan)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Lymphoblastic Leukemia
-
National Cancer Institute (NCI)CompletedB-cell Adult Acute Lymphoblastic Leukemia | Acute Undifferentiated Leukemia | Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia | B-cell Childhood Acute Lymphoblastic Leukemia | L1 Childhood Acute Lymphoblastic Leukemia | L2 Childhood Acute Lymphoblastic Leukemia | T-cell... and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingAcute Lymphoblastic Leukemia | Recurrent Adult Acute Lymphoblastic Leukemia | Adult B Acute Lymphoblastic Leukemia | Adult T Acute Lymphoblastic Leukemia | Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 | Adult L1 Acute Lymphoblastic Leukemia | Adult L2 Acute Lymphoblastic...United States
-
Autolus LimitedCompletedCD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell Acute Lymphoblastic Leukemia (ALL) (AMELIA)Recurrent Childhood Acute Lymphoblastic Leukemia | B Acute Lymphoblastic Leukemia | B-cell Acute Lymphoblastic Leukemia | Refractory Childhood Acute Lymphoblastic LeukemiaUnited Kingdom
-
Children's Oncology GroupNational Cancer Institute (NCI); ImmunoGen, Inc.WithdrawnRecurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Recurrent B Acute Lymphoblastic Leukemia | Refractory B Acute Lymphoblastic Leukemia | Recurrent Mixed Phenotype Acute Leukemia | Refractory Mixed Phenotype Acute Leukemia | Refractory T Acute Lymphoblastic Leukemia | Recurrent...
-
National Cancer Institute (NCI)CompletedRecurrent Childhood Acute Lymphoblastic Leukemia | L1 Childhood Acute Lymphoblastic Leukemia | L2 Childhood Acute Lymphoblastic Leukemia | T-cell Childhood Acute Lymphoblastic Leukemia | Non-T, Non-B Childhood Acute Lymphoblastic LeukemiaUnited States
-
University of BirminghamAstraZeneca; Cancer Research UKTerminatedAcute Lymphoblastic Leukemia | Acute Lymphoblastic Leukemia, Pediatric | Acute Lymphoblastic Leukemia, in Relapse | Acute Lymphoblastic Leukemia, Adult | Acute Lymphoblastic Leukemia RecurrentUnited Kingdom, Denmark, Netherlands
-
University College, LondonNot yet recruitingAcute Lymphoblastic Leukemia, Pediatric | Acute Lymphoblastic Leukemia, in Relapse | Acute Lymphoblastic Leukemia, Adult | Acute Lymphoblastic Leukemia With Failed Remission | Acute Lymphoblastic Leukemia Not Having Achieved Remission
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Graft Versus Host Disease | B-cell Childhood Acute Lymphoblastic Leukemia | L1 Childhood Acute Lymphoblastic Leukemia | L2 Childhood Acute Lymphoblastic Leukemia | T-cell Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia
-
Medical College of WisconsinChildren's Hospital and Health System Foundation, WisconsinRecruitingAcute Lymphoblastic Leukemia | Acute Lymphoblastic Leukemia, Pediatric | Acute Lymphoblastic Leukemia, in Relapse | Acute Lymphoblastic Leukemia Recurrent | Acute Lymphoblastic Leukemia With Failed Remission | Acute Lymphoblastic Leukemia Not Having Achieved RemissionUnited States
-
Therapeutic Advances in Childhood Leukemia ConsortiumEnzon Pharmaceuticals, Inc.TerminatedLymphoblastic Leukemia, Acute, Childhood | Leukemia, Lymphoblastic, Acute | Lymphoblastic Leukemia, Acute | Leukemia, Lymphoblastic, Acute, T CellUnited States, Australia
Clinical Trials on Dasatinib
-
Bristol-Myers SquibbCompletedPharmacokinetic Study in Healthy ParticipantsUnited States
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.Completed
-
Hyoung Jin KangNot yet recruitingAcute Lymphoblastic Leukemia, Pediatric
-
National Cancer Institute (NCI)WithdrawnHematopoietic and Lymphoid Cell Neoplasm | Advanced Lymphoma | Advanced Malignant Solid Neoplasm | Refractory Lymphoma | Refractory Malignant Solid Neoplasm | Refractory Plasma Cell MyelomaUnited States
-
National Cancer Institute (NCI)NRG OncologyTerminatedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Clear Cell Cystadenocarcinoma | Endometrial Clear Cell Adenocarcinoma | Recurrent Uterine Corpus CancerUnited States
-
Xspray Pharma ABQPS Bioserve India Pvt LimitedCompleted
-
Peking University Cancer Hospital & InstituteUnknownGastrointestinal Stromal TumorChina
-
Kanto CML Study GroupUnknownMyelogenous Leukemia, Chronic, Chronic PhaseJapan
-
Jonsson Comprehensive Cancer CenterBristol-Myers SquibbCompleted
-
Swiss Group for Clinical Cancer ResearchCompletedGastrointestinal Stromal TumorFrance, Switzerland, Germany, Finland