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Acute Lymphoblastic LeukemiaPhase 2NCT04845035

Pediatric-Inspired Chemotherapy Plus Tyrosine Kinase Inhibitor in Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

A Phase 2 study testing Dasatinib, Ponatinib and Berlin-Frankfurt-Münster Chemotherapy in people with Acute Lymphoblastic Leukemia, run by University of Michigan Rogel Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Lymphoblastic Leukemia
What is being tested?
Dasatinib, Ponatinib and Berlin-Frankfurt-Münster Chemotherapy
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Jan 2024to Jan 2029
Phase
Phase 2
Are there results?
None posted in the registry

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 ≥ 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.
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  • 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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

Other trials in United States

About this study

Official title: 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:

Read more
  • 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.

Being tested
Dasatinib, Ponatinib, Berlin-Frankfurt-Münster Chemotherapy, Methotrexate and Cytarabine
Keywords
Acute Lymphoblastic Leukemia, Dasatinib, Philadelphia chromosome, Ponatinib
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Philadelphia Chromosome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DasatinibDrug

    By mouth

  • PonatinibDrug

    By mouth

  • Berlin-Frankfurt-Münster ChemotherapyDrug

    with varied cycles, including Daunorubicin, Vincristine, Prednisone, Pegaspargase, Rituximab, Cytarabine, Mercaptopurine, Cyclophosphamide, Methotrexate, Doxorubicin, Thioguanine, and Dexamethasone

  • Methotrexate and CytarabineDrug

    Intrathecal

Study groups in NCT04845035
Study groupRoleWhat they receive
BFM + Tyrosine Kinase InhibitorExperimentalThis 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.
Receives: Drug: Dasatinib; Drug: Ponatinib; Drug: Berlin-Frankfurt-Münster Chemotherapy; Drug: Methotrexate and Cytarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of complete molecular remission (CMR) at the end of one cycle of Dasatinib + BFM

    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.

    Measured: Post day 36; up to day 43

Secondary outcomes (7)

  1. Rate of Adverse Events related to Dasatinib and Ponatinib

    Per NCI CTCAE v5.0 toxicity data, specifically:

    • for dasatinib: pulmonary hypertension (any grade) or grade ≥ 3 serositis/volume overload.
    • for ponatinib: arterial embolism (any grade) and grade ≥ 3 venous thromboembolism, heart failure, or pancreatitis

    Measured: 30 days after last treatment, up to approximately 3 years

  2. Percentage of participants who begin ponatinib post-induction that complete at least one cycle.

    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.

    Measured: At 18 weeks

  3. Complete hematologic (morphologic) remission (CHR) rate after induction

    Bone marrow assessed by morphologic review of both the aspirate smear and core biopsy

    Measured: After Remission Induction Phase I and at end of study treatment, up to approximately 3 years

  4. Complete cytogenic remission (CCyR) rate post induction

    Bone marrow aspirate assessed by karyotype and/or fluorescence in situ hybridization (FISH).

    Measured: After Remission Induction Phase I and at end of study treatment, up to approximately 3 years

  5. Complete molecular remission (CMR) rate

    Bone marrow aspirate analyzed by RT-qPCR.

    Measured: After Remission Induction Phase I and at end of study treatment, up to approximately 3 years

  6. Disease-free survival (DFS)

    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.

    Measured: up to five years after end of study treatment (approximately 8 years)

  7. Overall survival (OS).

    Overall Survival (OS) is defined as the length of time from the date of diagnosis that patients diagnosed with the disease are still alive.

    Measured: up to five years after end of study treatment (approximately 8 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2021
  2. Study startJan 2024 (estimated)
  3. Primary completionJan 2026 (estimated)
  4. Study completionJan 2029 (estimated)

Why it stopped: The PI plans to revise the study design in a new protocol

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04845035
Sponsor's protocol ID
UMCC 2018.144
Other IDs
HUM00171952
Status last verified
Feb 2024
First submitted
5 Apr 2021
Last updated
22 Feb 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dasatinib, Ponatinib and Berlin-Frankfurt-Münster Chemotherapy in people with Acute Lymphoblastic Leukemia, run by University of Michigan Rogel 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 13 inclusion and 30 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: withdrawn, as of the sponsor's last update on 22 Feb 2024. 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 phase mean?

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Rate of complete molecular remission (CMR) at the end of one cycle of Dasatinib + BFM (time frame: Post day 36; up to day 43). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04845035.

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 22 Feb 2024.

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