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B-cell Acute Lymphoblastic LeukemiaPhase 1NCT05016947

Venetoclax Plus Inotuzumab for B-ALL

A Phase 1 study testing Venetoclax, Dexamethasone and Inotuzumab Ozogamicin in people with B-cell Acute Lymphoblastic Leukemia and B-Cell Lymphoma, run by Dana-Farber Cancer Institute at 2 sites 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 research study is evaluating the safety and efficacy of administering venetoclax and inotuzumab ozogamicin in combination in patients with acute lymphoblastic leukemia (ALL) The names of the study drugs involved in this study are: Venetoclax Inotuzumab ozogamicin Dexamethasone Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Venetoclax, Dexamethasone and Inotuzumab Ozogamicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
2 sitesUnited States
Study dates
24 Sep 2021to 23 Dec 2026
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have histologically confirmed CD22+ B-ALL or B-LBL.
  • Note: CD22 must be detected on ≥ 20% of lymphoblasts by flow cytometry of peripheral blood, flow cytometry of bone marrow aspirate or tissue biopsy, or immunohistochemistry of the bone marrow or tissue biopsy.
  • Note: for R/R disease: ≥ 5% lymphoblasts must be documented in the diagnostic sample (blood, marrow, or tissue biopsy).
  • Note: Participants with B-LBL (confirmed CD22-positive extramedullary disease, but none or minimal marrow involvement) are eligible if eligibility criteria otherwise met.
  • Note: Participants with Philadelphia-chromosome positive B-ALL are eligible but must be refractory to 2 or more tyrosine kinase inhibitors (TKIs), refractory to ponatinib, or ineligible to receive all available TKIs.
  • Note: Participants with chronic myeloid leukemia (CML) in lymphoid blast crisis are eligible but must be refractory to 2 or more TKIs, refractory to ponatinib, or ineligible to receive all available TKIs.
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  • Participants must have disease that is relapsed or refractory (R/R) to 1 or more cycles of cytotoxic chemotherapy.
  • Note: There is no limit to number or type of prior therapies (prior inotuzumab ozogamicin is not permitted).
  • Note: Philadelphia-chromosome positive B-ALL patients previously treated with TKI are eligible without receiving cytotoxic chemotherapy if they are unsuitable for standard cytotoxic chemotherapy.
  • Participants be aged ≥ 18 years.
  • ECOG performance status of 0-3.
  • Adequate organ function.
  • Serum total bilirubin ≤ 1.5x upper limit of normal (ULN), unless due to Gilbert's syndrome or of non-hepatic origin (i.e. hemolysis).
  • ALT and AST ≤ 2.5x ULN, unless clearly due to disease, in which case ≤ 5x ULN is permissible.
  • Creatinine clearance of ≥ 30 mL/min calculated using Cockcroft-Gault formula or measured by 24-hour urine collection.
  • 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. Women of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. The effects of venetoclax and inotuzumab ozogamicin on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during treatment, and for at least 8 and 5 months after the last dose, respectively. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Medication list must be carefully reviewed to ensure no contra-indicated drug-drug interactions.
  • For participants with known evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be confirmed to be undetectable (and appropriate suppressive therapy must be initiated in consultation with an infectious disease expert, if indicated).
  • Participants with a known history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load confirmed.
  • Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. The treating investigator must review such cases with the overall PI prior to confirming eligibility.
  • Participants with prior HSCT or chimeric antigen receptor T-cell (CAR-T) therapy (autologous or allogeneic) are eligible if they are day +60 from cell infusion and do not have active Glucksberg grade 2 or higher graft versus host disease (GVHD). Patient must be off calcineurin inhibitor for 2 weeks.
  • Ability to understand and the willingness to sign and date written informed consent document.

Who cannot join

  • Absolute blast count of ≥25 K/µL prior to initiation of study treatment. Steroids, hydroxyurea, and/or vincristine may be used to reduce blast count.
  • Prior treatment with inotuzumab ozogamicin at any time.
  • Prior treatment with venetoclax for relapsed disease; if venetoclax used during first-line therapy, 60 or more days must have elapsed since last dose of venetoclax. Note: The number of patients with prior receipt of venetoclax will be capped at 50% of the participants enrolled in the dose expansion phase.
  • Treatment for ALL with chemotherapy within 14 days of first dose of study drugs except for hydroxyurea, steroids, vincristine, and/or intra-thecal chemotherapy.
  • Symptomatic central nervous systemic (CNS) disease and CNS-3 disease. Asymptomatic CNS-2 disease is permitted. Prior CNS disease is not an exclusion. See Appendix B for definition of CNS disease.
  • Participants with history of decompensated hepatic cirrhosis, veno-occlusive disease (VOD)/sinusoidal obstructive syndrome (SOS), or severe liver disease.
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  • Patient with uncontrolled intercurrent illness, or 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.
  • Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) except for alopecia.
  • Participants who are receiving any other investigational agents.
  • Participants receiving any medications or substances within 7 days that are strong CYP3A4 inhibitors (such as fluconazole, voriconazole, posaconazole, isavuconazole, and clarithromycin) or inducers (such as rifampin, rifabutin, phenytoin, carbamazepine, and St. John's Wort) of CY3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference (Appendix C). Of note, anti-fungal azole therapy may be re-introduced after venetoclax dose escalation as outlined in the protocol.
  • Participants who have consumed grapefruit, grapefruit products, Seville oranges (used in marmalade), or star fruit within 3 days prior to starting venetoclax.
  • Malabsorption syndrome or other conditions (such as inability to swallow pills) that preclude enteral route of venetoclax administration.
  • Participants with psychiatric illness/social situations that would limit adherence to study requirements.
  • Pregnant women are excluded from this study because the effects of venetoclax and inotuzumab ozogamicin on the developing human fetus are unknown with the potential for teratogenic or abortifacient effects. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax and inotuzumab ozogamicin and therefore breastfeeding should be discontinued.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: A Phase 1 Study of Venetoclax in Combination With Inotuzumab Ozogamicin for B-cell Acute Lymphoblastic Leukemia (B-ALL)

This research study is evaluating the safety and efficacy of administering venetoclax and inotuzumab ozogamicin in combination in patients with acute lymphoblastic leukemia (ALL)

The names of the study drugs involved in this study are:

  • Venetoclax
  • Inotuzumab ozogamicin
  • Dexamethasone
Read the detailed description

This is a phase I study of venetoclax in combination with inotuzumab ozogamicin for the treatment of CD22-positive (CD22+) B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma (B-LBL), hereafter referred to as "ALL," in patients with disease relapsed from or refractory (R/R) to prior intensive chemotherapy.

The U.S. Food and Drug Administration (FDA) has not approved venetoclax for ALL but it has been approved for other uses. Venetoclax is an oral (pill) chemotherapy that works by blocking the action of certain proteins in cancer cells that help those cells survive.

The U.S. Food and Drug Administration (FDA) has approved inotuzumab ozogamicin as a treatment option for ALL but not in combination with other drugs. Inotuzumab ozogamicin is an antibody-drug conjugate. An antibody-drug conjugate is a medication where a cancer drug (chemotherapy) is attached to an antibody, an immune system protein, that targets a specific protein on the cancer cell. Inotuzumab ozogamicin is combination of an antibody that targets the CD22 protein on ALL cells and calicheamicin, a chemotherapy compound that kills cancer cells. Once the antibody portion of inotuzumab ozogamicin binds to CD22 protein on cancer cells, the calicheamicin is released into the cell, where it damages the cancer cell's DNA and causes its death.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

Participants will receive study treatment for approximately 6-9 months depending on their response to the study treatment and followed for two years after completion of study.

It is expected that 20 to 32 people will take part in this research study.

Abbvie is supporting this research study by providing the study drug venetoclax and funding research tests and procedures.

Being tested
Venetoclax, Dexamethasone, Inotuzumab Ozogamicin
Keywords
B-cell Acute Lymphoblastic Leukemia, B-Cell Lymphoma, ALL
Medical subject headings
Burkitt Lymphoma, Lymphoma, B-Cell

What participants receive

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

  • VenetoclaxDrug

    Also called Venclexta

    Tablet, taken by mouth

  • DexamethasoneDrug

    Also called Decadron, Dexasone, Diodex, Hexadrol

    Taken orally

  • Inotuzumab OzogamicinDrug

    Also called Besponsa

    Intravenous infusion

Study groups in NCT05016947
Study groupRoleWhat they receive
Venetoclax + Inotuzumab Ozogamicin with DexamethasoneExperimentalPhased 28 day treatment cycles with lead in: Lead In Cycle: Dose escalated venetoclax 1x daily for days 1-3 with and Dexamethasone daily for days 1-3 lead in, 7 days total. Induction Cycle 1: Dose escalated venetoclax 1x daily for days 1-21, Dexamethasone daily for days 1-4, Inotuzumab ozogamicin on days 1, 8, and 15 Induction Cycle 2: Dose escalated venetoclax 1x daily for days and Inotuzumab ozogamicin on days 1, 8, and 15 Consolidation Cycles: Up to 5 cycles of dose escalated Venetoclax 1x daily for days and Inotuzumab ozogamicin on days 1, 8, and 15
Receives: Drug: Venetoclax; Drug: Dexamethasone; Drug: Inotuzumab Ozogamicin

What is being measured

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

  1. Maximum tolerated dose of venetoclax in combination with inotuzumab ozogamicin

    Descriptive analysis of highest dose of venetoclax that did not cause a dose limiting toxicity with toxicity type based CTCAE vs 5.0 criteria.

    Measured: Enrollment to end of treatment up to 9 months

Secondary outcomes (5)

  1. Morphologic response

    Proportion of participants who achieve hematologic complete remission with 90% confidence intervals

    Measured: Enrollment to end of treatment up to 9 months

  2. Measurable residual disease (MRD)-response

    Proportion of participants who become MRD-negative by multi-parameter flow cytometry with 90% confidence intervals

    Measured: Enrollment to end of treatment up to 9 months

  3. Event-free survival (EFS)

    Estimated by Kaplan-Meier method

    Measured: Enrollment to end of treatment up to 9 months

  4. Disease-free survival (DFS)

    Estimated by Kaplan-Meier method

    Measured: Enrollment to end of treatment up to 9 months

  5. Overall survival (OS).

    Estimated by Kaplan-Meier method

    Measured: Enrollment to end of treatment up to 9 months

Timeline

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

  1. First posted23 Aug 2021
  2. Study start24 Sep 2021
  3. Primary completion10 Jul 2023
  4. Study completion23 Dec 2026 (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
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05016947
Sponsor's protocol ID
21-196
Status last verified
Jan 2026
First submitted
17 Aug 2021
Last updated
29 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Publications

  • Luskin MR, Keating JH, Frost BF, Jaeckle SL, Shimony S, Flamand Y, Garcia JS, Stone RM, Booker M, Weizer CM, Ryan JA, Lee J, Galinsky IA, Shah SI, Smith E, Kulkarni A, Tolstorukov M, Chen EC, Winer ES, Letai A, Murakami MA, DeAngelo DJ. Venetoclax plus Inotuzumab Ozogamicin for Relapsed and Refractory Acute Lymphoblastic Leukemia. Blood. 2026 Sep 25:blood.2026035238. doi: 10.1182/blood.2026035238. Online ahead of print.

    PubMed 42789493

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax, Dexamethasone and Inotuzumab Ozogamicin in people with B-cell Acute Lymphoblastic Leukemia and B-Cell Lymphoma, run by Dana-Farber Cancer Institute at 2 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 22 inclusion and 14 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 29 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 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?

Maximum tolerated dose of venetoclax in combination with inotuzumab ozogamicin (time frame: Enrollment to end of treatment up to 9 months). 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 NCT05016947, 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 29 Jan 2026.

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