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B Acute Lymphoblastic LeukemiaPhase 1NCT05157971

Venetoclax and a Pediatric-Inspired Regimen for the Treatment of Newly Diagnosed B Cell Acute Lymphoblastic Leukemia

A Phase 1 study testing Cyclophosphamide, Cytarabine and Daunorubicin Hydrochloride in people with B Acute Lymphoblastic Leukemia and Ph-Like Acute Lymphoblastic Leukemia, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase I trial tests the safety, side effects, and best dose of venetoclax in combination with a pediatric-inspired chemotherapy regimen known as C10403 in treating patients with newly diagnosed B cell acute lymphoblastic leukemia. Read more about this study

Who is it for?
Ages 18 to 54 years
What is being tested?
Cyclophosphamide, Cytarabine and Daunorubicin Hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
17 Mar 2022to 12 Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 to 54 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Documented informed consent of the participant and/or legally authorized representative
  • Age between 18 and 54 years
  • Eastern Cooperative Oncology Group (ECOG) =< 2
  • Histologically confirmed B-cell ALL according to World Health Organization criteria
  • Note: Lymphoblastic leukemia is included as long as there is bone marrow involvement
  • Newly diagnosed disease with >= 5% blasts in the marrow
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  • White blood cell count less than 25 x 10^9/L prior to initiation of venetoclax. Cytoreduction with hydroxyurea or steroid or a single dose of intrathecal chemotherapy prior to treatment may be required (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease or underlying leukemia, =< 3 X ULN) (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • Unless it is related to underlying leukemia
  • Alanine aminotransferase (ALT) =< 2.5 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • Unless it is related to underlying leukemia
  • Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
  • Left ventricular ejection fraction (LVEF) >= 50%
  • Note: Echocardiogram to be performed within 42 days prior to day 1 of protocol therapy
  • Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. (performed within 14 days prior to Day 1 of protocol therapy unless otherwise stated)
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential* to use an effective method of birth control (non-hormonal) or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only

Who cannot join

  • Leukemia-based therapy with chemotherapy with the exception of:
  • Cytoreduction with steroid or hydroxyurea or a single dose of intrathecal chemotherapy is allowed before initiating the study
  • Strong or moderate CYP3A4 inducers within 14 days prior to day 1 of protocol therapy
  • Subjects who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the first dose of study drug
  • Live vaccines
  • Philadelphia chromosome positive (Ph+; t(9;22)), MLL-rearrangement, t(12;21), and t(1;19)
Show all 18Show fewer
  • T cell ALL
  • Class III/IV cardiovascular disability according to the New York Heart Association Classification. Subjects with controlled, asymptomatic atrial fibrillation can enroll
  • Parenchymal central nervous system (CNS) involvement requiring cranial radiation
  • Participants with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of enrollment
  • History of acute cardiovascular ischemic event, i.e., myocardial infarction or unstable angina within 6 months of enrollment
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  • Clinically significant uncontrolled illness
  • Uncontrolled active infection
  • Other active malignancy
  • Females only: Pregnant or breastfeeding
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase 1 Study Combining Venetoclax With a Pediatric-Inspired Regimen for Newly Diagnosed Adults With B Cell Ph-Like Acute Lymphoblastic Leukemia

This phase I trial tests the safety, side effects, and best dose of venetoclax in combination with a pediatric-inspired chemotherapy regimen known as C10403 in treating patients with newly diagnosed B cell acute lymphoblastic leukemia. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. The C10403 regimen is composed of the chemotherapy drugs cytarabine, cyclophosphamide, daunorubicin, mercaptopurine, pegaspargase, vincristine, and methotrexate, all which 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. It also consists of prednisone, which is an anti-inflammatory drug that lowers the body's immune response and is used with other drugs in the treatment of some types of some types of cancer. This study may help researchers learn if adding venetoclax to the pediatric-inspired C10403 regimen can be tolerated and help treat older patients.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety and tolerability of combining venetoclax with the C10403 regimen backbone during induction and consolidation in newly diagnosed adults with B cell acute lymphoblastic leukemia (ALL).

II. To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose/schedule (RP2D) of venetoclax in combination with the C10403 regimen.

SECONDARY OBJECTIVES:

  1. To estimate complete response (CR) after induction. II. To estimate composite CR (CR or CR with incomplete hematologic recovery [CRi] or CR with partial hematologic recovery [CRh]) after induction.

III. To estimate minimal residual disease (MRD) negativity after induction. IV. To estimate MRD negativity after consolidation. V. To estimate CR after induction for Philadelphia (Ph)-like ALL. VI. To estimate CR/CRi/CRh after induction for Ph-like ALL. VII. To estimate MRD negativity after induction for Ph-like ALL. VIII. To estimate MRD negativity after consolidation for Ph-like ALL. IX. To estimate leukemia-free survival (LFS) and overall survival (OS).

OUTLINE:

INDUCTION: Patients receive venetoclax orally (PO) on days 1-14. Patients also receive cytarabine intrathecally (IT) on day 1, prednisone PO twice daily (BID) on days 1-28, vincristine intravenously (IV) on days 1, 8, 15 and 22, daunorubicin IV on days 1, 8, 15 and 22, pegaspargase intramuscularly (IM) or IV on day 4, and methotrexate IT on days 8 and 29 (and also on days 15 and 22 for central nervous system [CNS]3 patients) in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD) or partial response (PR) after Induction proceed to Extended Induction. Patients with CR, CRi, or CRh after Induction proceed to Consolidation.

EXTENDED INDUCTION: Patients receive venetoclax PO on days 1-7, prednisone PO BID on days 1-14, vincristine IV on days 1 and 8, daunorubicin IV on day 1, and pegaspargase IM or IV on day 4 in the absence of disease progression or unacceptable toxicity. Patients with CR, CRi, or CRh after Extended Induction proceed to Consolidation.

CONSOLIDATION: Patients receive venetoclax PO on days 1-14, cyclophosphamide IV on days 1 and 29, cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32 and 36-39, mercaptopurine PO on days 1-14 and 29-42, vincristine IV on days 15, 22, 43 and 50, pegaspargase IM or IV on days 15 and 43, and methotrexate IT on days 1, 8, 15 and 22 (omit on days 15 and 22 for CNS3 patients) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year.

Being tested
Cyclophosphamide, Cytarabine, Daunorubicin Hydrochloride, Mercaptopurine, Methotrexate
Medical subject headings
Burkitt Lymphoma

What participants receive

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

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • CytarabineDrug

    Also called .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

    Given SC, IV or IT

  • Daunorubicin HydrochlorideDrug

    Also called Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin

    Given IV

  • MercaptopurineDrug

    Also called 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine

    Given PO

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IT

  • PegaspargaseDrug

    Also called L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-Asparaginase

    Given IM or IV

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin

    Given IV

Study groups in NCT05157971
Study groupRoleWhat they receive
Treatment (venetoclax, C10403 regimen)ExperimentalSee Detailed Description
Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Prednisone; Drug: Venetoclax; Drug: Vincristine Sulfate

What is being measured

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

  1. Incidence of adverse events

    Will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, frequency, probable association with the study treatment and reversibility or outcome.

    Measured: Up to 30 days after completion of treatment

  2. Dose limiting toxicity

    Defined as any toxicities that occur during cycle 1, per CTCAE version 5.0, and are considered at least possibly related to venetoclax or the combination of venetoclax and C10403. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, frequency, probable association with the study treatment and reversibility or outcome.

    Measured: During cycle 1 (4 weeks)

Secondary outcomes (12)

  1. Complete response (CR) after induction +/- extended induction

    Will be estimated and the 95% Clopper Pearson binomial confidence interval (CI) will be estimated.

    Measured: At week 4 or 6

  2. Complete response (CR) after consolidation

    Will be estimated and the 95% Clopper Pearson binomial CI will be estimated.

    Measured: Up to 1 year

  3. Composite complete response (CR) (CR/ CR with incomplete hematologic recovery [CRi]/ CR with partial hematologic recovery [CRh]) after induction +/- extended induction

    Will be estimated and the 95% Clopper Pearson binomial CI will be estimated.

    Measured: At week 4 or 6

  4. Minimal residual disease (MRD) negativity after induction +/- extended induction

    Defined as residual leukemia < 0.01% by flow cytometry. Will be estimated and the 95% Clopper Pearson binomial CI will be estimated.

    Measured: At day 28

  5. Minimal residual disease (MRD) negativity after consolidation

    Will be estimated and the 95% Clopper Pearson binomial CI will be estimated.

    Measured: At week 12

  6. Complete response (CR) after induction +/- extended induction for Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL)

    Will be estimated and the 95% Clopper Pearson binomial CI will be estimated.

    Measured: At week 4 or 6

  7. Complete response (CR) after consolidation for Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL)

    Will be estimated and the 95% Clopper Pearson binomial CI will be estimated.

    Measured: Up to 1 year

  8. Composite complete response (CR) (CR/ CR with incomplete hematologic recovery [CRi]/ CR with partial hematologic recovery [CRh]) after induction +/- extended induction for Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL)

    Will be estimated and the 95% Clopper Pearson binomial CI will be estimated.

    Measured: At week 4 or 6

  9. Minimal residual disease (MRD) negativity after induction +/- extended induction for Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL)

    Will be estimated and the 95% Clopper Pearson binomial CI will be estimated.

    Measured: At week 4 or 6

  10. Minimal residual disease (MRD) negativity after consolidation for Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL)

    Will be estimated and the 95% Clopper Pearson binomial CI will be estimated.

    Measured: At week 12

  11. Leukemia-free survival

    Will be estimated using the Kaplan-Meier product-limit method.

    Measured: Up to 1 year

  12. Overall survival

    Will be estimated using the Kaplan-Meier product-limit method.

    Measured: Up to 1 year

Timeline

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

  1. First posted15 Dec 2021
  2. Study start17 Mar 2022
  3. Primary completion12 Apr 2027 (estimated)
  4. Study completion12 Apr 2027 (estimated)

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05157971
Sponsor's protocol ID
21134
Other IDs
NCI-2021-09185, 21134, P30CA033572
Status last verified
May 2026
First submitted
2 Dec 2021
Last updated
28 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, Cytarabine and Daunorubicin Hydrochloride in people with B Acute Lymphoblastic Leukemia and Ph-Like Acute Lymphoblastic Leukemia, run by City of Hope Medical 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 19 inclusion and 18 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: under way, not looking for participants, as of the sponsor's last update on 28 May 2026. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Incidence of adverse events (time frame: Up to 30 days after completion of treatment). The study lists 2 primary outcomes in all. 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 NCT05157971.

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 28 May 2026.

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