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LeukemiaPhase 1/2NCT03319901

Venetoclax and Chemotherapy as Frontline Therapy in Older Patients and Patients With Relapsed/Refractory ALL

A Phase 1/2 study testing Venetoclax and Standard Chemotherapy in people with Leukemia, run by Dana-Farber Cancer Institute at 5 sites in United States.

Active, not recruiting

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

Official record
Search all trials

Trial summary

This research study is studying a medication called Venetoclax and a chemotherapy regimen as a possible treatment for Acute Lymphoblastic Leukemia. The drugs involved in this study are: Venetoclax Standard Chemotherapy (which includes cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia
What is being tested?
Venetoclax and Standard Chemotherapy
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
82 participants
Where
5 sitesUnited States
Study dates
30 Oct 2017to 30 May 2028
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with previously untreated acute lymphoblastic leukemia (B-cell or T-cell)
  • Bone marrow involvement with ≥20% lymphoblasts
  • Age ≥ 60 Years
  • OR
  • Patients with relapsed or refractory acute lymphoblastic leukemia (B-cell or T-cell) defined as receiving one or more cytotoxic containing regimens
  • Bone marrow involvement with ≥5% lymphoblasts
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  • Age ≥ 18 Years
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Refer to Appendix D)
  • Adequate organ function
  • Serum total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN, unless clearly due to disease involvement
  • Creatinine clearance >50 mL/min (calculated according to institutional standards or using Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula)
  • Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use an effective contraception method during the study and for 30 days following the last dose of study drug. Women of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
  • Patients or their legally authorized representative must provide written informed consent

Who cannot join

  • Ph-positive ALL, Burkitt's leukemia/lymphoma, or lymphoblastic lymphoma
  • Patient is pregnant or breastfeeding
  • Patients with uncontrolled infection
  • Hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
  • Major surgery or radiation therapy within 4 weeks prior to the first study dose
  • Systemic chemotherapy/radiotherapy/investigational therapy within 14 days (with the exception of hydroxyurea and/or dexamethasone, or one dose of cytarabine) prior to starting therapy
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  • Symptomatic or untreated leptomeningeal disease or spinal cord compression
  • Patients with active heart disease (New York Heart Association (NYHA) class 3-4 as assessed by history and physical examination, unstable angina/stroke/myocardial infarction within the last 6 months)
  • Patients with a cardiac ejection fraction (as measured by either Multi Gated Acquisition (MUGA) or echocardiogram (EKG)) <40%
  • History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses)
  • Concurrent use of warfarin
  • Received Cytochrome P450 3A (CYP3A) inhibitors (such as fluconazole, ketoconazole, voriconazole, and clarithromycin) within 3 days of starting venetoclax; received strong CYP3A inducers (such as rifampin, rifabutin, phenytoin, carbamazepine, and St. John's Wort) within 3 days of starting venetoclax
  • Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax
  • Prior treatment with venetoclax
  • Malabsorption syndrome or other conditions that preclude enteral route of administration
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of Chicago

    Chicago, Illinois, 60637

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Intermountain LDS Hospital

    Salt Lake City, Utah, 84143

Other trials in United States

About this study

Official title: A Phase Ib Study of the Combination of Venetoclax With Chemotherapy as Frontline Therapy in Older Patients and Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia

This research study is studying a medication called Venetoclax and a chemotherapy regimen as a possible treatment for Acute Lymphoblastic Leukemia.

The drugs involved in this study are:

  • Venetoclax
  • Standard Chemotherapy (which includes cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, 6-mercaptopurine, etoposide, and cytarabine
Read the detailed description

This research study is a Phase I clinical trial, which tests the safety of an investigational drug and drug combination and also tries to define the appropriate dose of the investigational drug and drug combination to use for further studies. "Investigational" means that the drug and drug combination is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved Venetoclax for this specific disease, but it has been approved for other uses.

Venetoclax is an inhibitor of Bcl-2. Bcl-2 is critical for keeping cancer cells alive.

By inhibiting Bcl-2, venetoclax promotes cancer cell death. This drug is currently being used in other clinical trials for people with certain types of leukemia, lymphoma, and multiple myeloma. There is some evidence from those and other laboratory trials that venetoclax may kill cancer cells and cause tumors to shrink.

In this research study, the investigators are investigating how safe the combination of Venetoclax and standard chemotherapy is and how it affects this disease.. The participant will be given Venetoclax alone first and the standard chemotherapies will be given in combination. This study aims to provide information to help determine the dose of Venetoclax , in combination with standard chemotherapy, affects this disease the best and which dose is the safest.

Conditions
Leukemia
Being tested
Venetoclax, Standard Chemotherapy
Keywords
Leukemia
Medical subject headings
Leukemia

What participants receive

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

  • VenetoclaxDrug

    Also called ABT199

    Venetoclax is an inhibitor of Bcl-2. Bcl-2 is critical for keeping cancer cells alive.

    By inhibiting Bcl-2, venetoclax promotes cancer cell death.

  • Standard ChemotherapyDrug

    Standard treatment of chemotherapy is administered

Study groups in NCT03319901
Study groupRoleWhat they receive
Venetoclax + ChemotherapyExperimental* Venetoclax is administered orally once daily for 21 days in each cycle * Standard Chemotherapy will be administered every 28 days
Receives: Drug: Venetoclax; Drug: Standard Chemotherapy

What is being measured

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

  1. Maximum Tolerated Dose

    To determine the maximum tolerated dose (MTD) of venetoclax in combination with chemotherapy in patients with newly diagnosed Acute Lymphoblastic Leukemia (ALL)

    Measured: 2 years

Secondary outcomes (16)
  1. To Evaluate The Safety of the Combination

    To evaluate the safety of this combination in a dose expansion cohort.

    The proportion of patients having a grade 3 or higher adverse event will be estimated with a 95% confidence interval in the expansion cohort.

    Measured: 2 years

  2. Complete Response

    To determine the efficacy: complete response (CR) with incomplete marrow recovery (CRi) of venetoclax in combination with chemotherapy in patients with newly diagnosed ALL

    Measured: 2 years

  3. Progression Free Survival

    To determine the duration of response: progressive-free survival (PFS) and overall survival (OS) of venetoclax in combination with chemotherapy in patients with newly diagnosed ALL

    Measured: 2 years

  4. Overall Survival

    To determine the duration of response: progressive-free survival (PFS) and overall survival (OS) of venetoclax in combination with chemotherapy in patients with newly diagnosed ALL

    Measured: 2 years

  5. Minimal Residual Disease

    To determine the rate of minimal residual disease (MRD) negativity in patients achieving CR/CRi and its correlation with disease-free survival (DFS) and OS

    Measured: 2 years

  6. Disease Free Survival

    To determine the rate of minimal residual disease (MRD) negativity in patients achieving CR/CRi and its correlation with disease-free survival (DFS) and OS

    Measured: 2 years

  7. Change in expression of BCL-2 family proteins: BCL-2

    To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts.

    The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BCL-2 and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi.

    This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI.

    Measured: 2 years

  8. Change in expression of BCL-2 family proteins: BCL-XL

    To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts.

    The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BCL-XL and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi.

    This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI.

    Measured: 2 years

  9. Change in expression of BCL-2 family proteins: MCL-1 (anti-apoptotic)

    To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts.

    The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including MCL-1 (anti-apoptotic) and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi.

    This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI.

    Measured: 2 years

  10. Change in expression of BCL-2 family proteins: BCL-2 homology 3 (BH3)

    To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts.

    The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BCL-2 homology 3 (BH3) and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi.

    This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI.

    Measured: 2 years

  11. Change in expression of BCL-2 family proteins: BIM

    To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts.

    The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BIM and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi.

    This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI.

    Measured: 2 years

  12. Change in expression of BCL-2 family proteins: BID

    To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts.

    The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BID and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi.

    This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI.

    Measured: 2 years

  13. Change in expression of BCL-2 family proteins: BAD

    To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts.

    The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including BAD and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi.

    This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI.

    Measured: 2 years

  14. Change in expression of BCL-2 family proteins: NOXA

    To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts.

    The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including NOXA and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi.

    This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI.

    Measured: 2 years

  15. Change in expression of BCL-2 family proteins: PUMA

    To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts.

    The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including PUMA and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi.

    This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI.

    Measured: 2 years

  16. Change in expression of BCL-2 family proteins: HRK (pro-apoptotic)

    To measure expression and function of Bcl-2 family proteins and its modulation by venetoclax in ALL blasts.

    The change in expression of BCL-2 family proteins from baseline to the time of each response assessment will be measured including HRK (pro-apoptotic) and summary statistics including the median and interquartile range of the change will be reported for all patients in the expansion cohort and also summarized for those achieving a CR/CRi and those patients who do not achieve a CR/CRi.

    This is based on section 9.1: We plan to collect bone marrow and peripheral blood samples at baseline, at the time of clinical response assessment and at the time of progression for correlative studies. These will be done in the laboratory of Dr. Marina Konopleva at MDACC and Dr. Tony Letai at DFCI.

    Measured: 2 years

Timeline

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

  1. First posted24 Oct 2017
  2. Study start30 Oct 2017
  3. Primary completion25 Nov 2025
  4. Study completion30 May 2028 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
82 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03319901
Sponsor's protocol ID
16-648
Status last verified
May 2026
First submitted
28 Sep 2017
Last updated
1 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Luskin MR, Shimony S, Keating J, Winer ES, Garcia JS, Stone RM, Jabbour E, Flamand Y, Stevenson K, Ryan J, Zeng Z, Letai A, Konopleva M, Jain N, DeAngelo DJ. Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia. Blood Adv. 2025 Feb 11;9(3):617-626. doi: 10.1182/bloodadvances.2024014405.

    PubMed 39546748

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Venetoclax and Standard Chemotherapy in people with Leukemia, run by Dana-Farber Cancer Institute at 5 sites 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 14 inclusion and 16 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 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites 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 combined 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.

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?

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?

Maximum Tolerated Dose (time frame: 2 years). 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 NCT03319901, which also lists 1 linked publication.

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 1 Jun 2026.

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