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Recurrent B Acute Lymphoblastic LeukemiaPhase 1/2NCT03808610

Low-Intensity Chemotherapy and Venetoclax in Treating Patients With Relapsed or Refractory B- or T-Cell Acute Lymphoblastic Leukemia

A Phase 1/2 study testing Cyclophosphamide, Cytarabine and Dexamethasone in people with Recurrent B Acute Lymphoblastic Leukemia and Recurrent T Acute Lymphoblastic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I/II trial studies the side effects and best dose of venetoclax and how well it works in combination with low-intensity chemotherapy in patients with B- or T-cell acute lymphoblastic leukemia that has not responded to treatment or that has come back. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Cytarabine and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
1 siteUnited States
Study dates
3 Apr 2019to 5 May 2026
Phase
Phase 1/2
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

  • Diagnosis of one of the following
  • Patients ≥ 18 years of age with relapsed/refractory B- or T-cell ALL (for phase II only)
  • Patients ≥ 60 years of age with previously untreated B- or T-cell ALL. Patients <60 years of age may be enrolled if they are considered unfit for intensive chemotherapy
  • Patients ≥ 60 years of age with previously treated B- or T-cell ALL who received 1-2 courses of any frontline chemotherapy. Patients <60 years of age may be enrolled if they are considered unfit for intensive chemotherapy
  • If they achieved CR/CRi, they are assessable only for event-free and overall survival
  • If they failed to achieve CR/CRi, they are assessable for response, event-free, and overall survival
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  • Performance status ≤ 3 (Eastern Cooperative Oncology Group [ECOG] Scale)
  • Adequate liver and renal function as defined by the following criteria:
  • Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) ≤ 3 x ULN, unless due to disease involvement of the liver or hemolysis, in which case an ALT ≤ 10 x ULN is acceptable
  • Aspartate aminotransferase (AST) ≤ 3 x ULN, unless due to disease involvement of the liver or hemolysis, in which case an ALT ≤ 10 x ULN is acceptable
  • Creatinine clearance ≥ 30 mL/min
  • INR ≤ 1.5 x ULN and aPTT . 1.5 x ULN
  • For females of childbearing potential, a negative pregnancy test must be documented within 1 week of starting treatment
  • Female and male patients who are fertile must agree to use an effective form of contraception (birth control methods while on study, such as birth control pills or injections, intrauterine devices [IUDs]), or double-barrier methods (for example, a condom in combination with spermicide) with their sexual partners for 4 months after the end of treatment
  • Signed informed consent

Who cannot join

  • Patients with Philadelphia chromosome-positive ALL or Burkitt leukemia
  • Patients who are willing and eligible to receive intensive chemotherapy (only for patients enrolling in frontline cohort)
  • Active serious infection not controlled by oral or intravenous antibiotics
  • Known CNS leukemia requiring radiation
  • Active GVHD
  • 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
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  • Known hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
  • Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
  • Patients with a cardiac ejection fraction (as measured by either multigated acquisition [MUGA] or echocardiogram) < 40%
  • Received moderate or strong CYP3A inhibitors or strong CYP3A inducers within 7 days of starting venetoclax
  • Received medication that interferes with coagulation or platelet function within 7 days prior to the first dose of study drug or during the study treatment period
  • Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax
  • Prior history of treatment with navitoclax.
  • 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. Exception: Treatment with hydroxyurea and/or dexamethasone are allowed prior to study treatment, without window of exclusion
  • 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); diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  • Patient with total serum bilirubin > 1.5 x upper limit of normal (ULN).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I/II Study of the Combination of Low-Intensity Chemotherapy and Venetoclax (ABT-199) in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

This phase I/II trial studies the side effects and best dose of venetoclax and how well it works in combination with low-intensity chemotherapy in patients with B- or T-cell acute lymphoblastic leukemia that has not responded to treatment or that has come back. Venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, including vincristine, cyclophosphamide, dexamethasone, rituximab, methotrexate, and cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax with low-intensity chemotherapy may work better in treating patient with B- or T-cell acute lymphoblastic leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose (MTD) and dose-limited toxicities (DLTs) of venetoclax in combination with low-intensity chemotherapy in patients with relapsed/refractory acute lymphoblastic leukemia (ALL) (Phase I).

II. Evaluate the overall response rate (complete response [CR] + CR with inadequate count recovery [CRi]) of the regimen after 2 cycles. (Phase II)

SECONDARY OBJECTIVES:

  1. Evaluate other clinical efficacy endpoints (minimal residual disease [MRD] negativity, duration of response [DOR], event-free survival [EFS] and overall survival [OS]).

II. Determine the safety of the combination regimen.

EXPLORATORY OBJECTIVES:

  1. To correlate apoptotic protein expression and Bcl-2 dependency on response and resistance to the combination regimen.

OUTLINE: This is a phase I, dose-escalation study of venetoclax, followed by a phase II study.

CHEMOTHERAPY AND VENETOCLAX:

CYCLE 1: Patients receive venetoclax orally (PO) once daily (QD) on days 1-21, vincristine intravenously (IV) over 15 minutes on days 7 and 17, cyclophosphamide IV twice daily (BID) over 3 hours on days 7-9, and dexamethasone IV over 30 minutes or PO QD on days 7-10 and 17-20. Patients may also receive rituximab IV over 4-6 hours on days 7 and 17 per physician discretion.

CYCLES 2, 4, 6, and 8: Patients receive venetoclax PO QD on days 1-21, methotrexate IV over 24 hours on day 1, and cytarabine IV BID over 3 hours on days 2 and 3. Patients may also receive rituximab IV over 4-6 hours on days 1 and 8 per physician discretion.

CYCLES 3, 5, and 7: Patients receive venetoclax PO QD on days 1-21, cyclophosphamide IV BID over 3 hours on days 1-3, vincristine IV over 15 minutes on days 1 and 11, and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients may also receive rituximab IV over 4-6 hours on days 1 and 11 per physician discretion.

T-CELL ALL: After the first 4 cycles, patients receive nelarabine IV over 2 hours on days 1-5 and pegaspargase IV over 2 hours on day 5. Cycles repeat every 28 days for 2 cycles (after cycle 4 and 5) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients may receive prednisone PO QD on days 1-5, vincristine IV over 15 minutes on day 1, and venetoclax, PO QD on days 1-21. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

T-CELL ALL (MAINTENANCE THERAPY): After the first 5 cycles of maintenance therapy, patients who received nelarabine and pegaspargase will receive nelarabine IV QD over 2 hours on days 1-5 and pegaspargase IV over 2 hours on day 5 during maintenance cycles 6 and 7 instead of prednisone, vincristine, and venetoclax.

After completion of study treatment, patients are followed up for 30 days and then every 3 months thereafter.

Medical subject headings
Burkitt Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-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 IV

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given IV or PO

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IV

  • NelarabineDrug

    Also called 2-Amino-6-methoxypurine arabinoside, 506U78, Arranon, Compound 506U78

    Given IV

  • PegaspargaseDrug

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

    Given IV

  • PrednisoneDrug

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

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • VenetoclaxDrug

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

    Given PO

  • VincristineDrug

    Also called LEUROCRISTINE, VCR, Vincrystine

    Given IV

Study groups in NCT03808610
Study groupRoleWhat they receive
Experimental (venetoclax, vincristine, cyclophosphamide)ExperimentalSee Detailed Description.
Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Methotrexate; Drug: Nelarabine; Drug: Pegaspargase; Drug: Prednisone; Biological: Rituximab; Drug: Venetoclax; Drug: Vincristine

What is being measured

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

  1. Maximum tolerated dose (MTD) (Phase I)

    The MTD is the highest dose level in which < 2 patients of 6 develop first cycle dose-limiting toxicity (DLT).

    Measured: Up to 28 days

  2. DLT (Phase I)

    A non-hematologic DLT is defined as a clinically significant (as assessed by treating physician) grade 3 or 4 adverse event or abnormal laboratory value (according to Common Terminology Criteria for Adverse Events [CTCAE] criteria). Toxicity type, severity and attribution will be summarized for each patient using frequency tables.

    Measured: Up to 28 days

Secondary outcomes (6)

  1. Overall response rate (Phase II)

    Will be defined as the percentage of patients achieving a complete response (CR) or CR with inadequate count recovery (CRi). Will estimate the overall response (OR) for the combination treatment, along with the 95% credible interval.

    Measured: Up to 56 days (2 courses)

  2. Minimal residual disease (MRD) negativity

    Will be summarized using descriptive statistics such as mean, standard deviation, median and range.

    Measured: Up to 4 years

  3. Duration of response (DOR)

    Will be summarized using descriptive statistics such as mean, standard deviation, median and range. The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.

    Measured: Up to 4 years

  4. Event-free survival (EFS)

    The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.

    Measured: From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 4 years

  5. Overall survival (OS)

    The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.

    Measured: From the first day of treatment to time of death from any cause, assessed up to 4 years

  6. Incidence of adverse events

    Will be summarized using descriptive statistics such as mean, standard deviation, median and range.

    Measured: Up to 4 years

Timeline

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

  1. First posted17 Jan 2019
  2. Study start3 Apr 2019
  3. Primary completion5 May 2026
  4. Study completion5 May 2026

Why it stopped: \<75% participation

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
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03808610
Sponsor's protocol ID
2016-0629
Other IDs
NCI-2018-03360, 2016-0629
Status last verified
May 2026
First submitted
16 Jan 2019
Last updated
13 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Short NJ, Jabbour E, Jain N, Senapati J, Nasr L, Haddad FG, Li Z, Hsiao YC, Yang JJ, Pemmaraju N, Ohanian M, Wierda WG, Montalban-Bravo G, Borthakur G, Han L, Xiao L, Huang X, Abramova R, Zhao M, Garris R, Konopleva M, Ravandi F, Kantarjian H. A phase 1/2 study of mini-hyper-CVD plus venetoclax in patients with relapsed/refractory acute lymphoblastic leukemia. Blood Adv. 2024 Feb 27;8(4):909-915. doi: 10.1182/bloodadvances.2023012231.

    PubMed 38207208

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cyclophosphamide, Cytarabine and Dexamethasone in people with Recurrent B Acute Lymphoblastic Leukemia and Recurrent T Acute Lymphoblastic Leukemia, run by M.D. Anderson 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 16 inclusion and 17 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: stopped early, as of the sponsor's last update on 13 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 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?

The study was stopped early (reason given: \<75% participation). Results are not available in the source record.

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 (MTD) (Phase I) (time frame: Up to 28 days). 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 NCT03808610, 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 13 May 2026.

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