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Chronic Lymphocytic LeukemiaPhase 1SAVENCT04843904

Safe Accelerated Venetoclax Escalation in CLL

A Phase 1 study testing Venetoclax, Obinutuzumab and Rituximab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Dana-Farber Cancer Institute 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 research study is trying to determine which patients with newly diagnosed or relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), as grouped by their risk for tumor lysis syndrome (TLS), are able to safely tolerate an accelerated, daily venetoclax dose ramp-up rather than… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Venetoclax, Obinutuzumab and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
14 Apr 2021to 2 Jun 2030
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

  • Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma per IW-CLL 201814 requiring therapy based on at least one of the following criteria as listed below:
  • Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin <11.0 g/L) and/or thrombocytopenia (platelets <100 x 109/L)
  • Massive (≥6 cm below the left costal margin), progressive, or symptomatic splenomegaly
  • Massive nodes (at least 10 cm longest diameter), progressive, or symptomatic
  • lymphadenopathy
  • Progressive lymphocytosis with an increase of more than 50% over a 2-month period or LDT of <6 months. Lymphocyte doubling time may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months.
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  • Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy
  • Documented constitutional symptoms, defined as 1 or more of the following disease related symptoms or signs: unintentional weight loss >10% within 6 months prior to screening, significant fatigue (inability to work or perform usual activities), fevers >100.5° F or 38.0° C for 2 or more weeks prior to screening without evidence of infection, night sweats for more than 1 month prior to screening without evidence of infection
  • Both previously untreated and relapsed or refractory patients will be eligible, including those who will be receiving venetoclax as monotherapy or in combination with anti-CD20 monoclonal antibody therapy
  • Age greater or equal to 18 years
  • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
  • Patients must meet the following hematologic criteria at screening, unless they have significant bone marrow involvement of CLL confirmed on biopsy:
  • Absolute neutrophil count ≥1000 cells/mm3. Growth factor is allowed in order to achieve this
  • Platelet count ≥25,000 cells/mm3 (25 x 109/L) independent of transfusion within 7 days of screening
  • Adequate hepatic function defined as:
  • Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN), bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
  • Adequate renal function as defined as:
  • Serum creatinine ≤1.5 times the ULN or creatinine clearance ≥ 50 mL/min using a 24-hour urine collection
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal, barrier method or abstinence) prior to study entry and for the duration of study participation
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Treatment with venetoclax within the past 6 months
  • Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leukemia)
  • Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, surgery within 2 weeks of Cycle 1/Day 1 with the following exceptions:
  • CD20 antibody therapy (i.e. rituximab or obinutuzumab) if it is being used as part of the venetoclax regimen (see inclusion criteria 3.1.2)
  • For patients on targeted therapies, a washout of least five half lives is required
  • Patients who experience clinical deterioration may start therapy after a shorter washout period with prior approval by the PI
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  • Corticosteroid therapy (prednisone or equivalent <=20 mg daily) is allowed
  • Confirmed central nervous system involvement
  • Allogeneic hematologic stem cell transplant within 6 months of starting study treatment or active graft vs. host disease (GVHD) requiring treatment or prophylaxis
  • Active malignancy requiring therapy that would interact with venetoclax as per the discretion of the treating investigator
  • Any active systemic infection requiring IV antibiotics or other uncontrolled, active infections
  • Known history of human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV)
  • Major surgery within 4 weeks of first dose of study drug
  • Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months of initial dosing on study
  • Use of Coumadin for anticoagulation (other anticoagulants permitted)
  • Lactating or pregnant
  • Concurrent administration of medications or foods that are strong inhibitors or inducers of CYP3A . The concomitant use of drugs or foods that are strong or moderate inhibitors or inducers of CYP3A are not allowed beginning 1 week prior to the first dose of venetoclax.
  • Patients with ongoing use of prophylactic antibiotics are eligible as long as there is no evidence of active infection and the antibiotic is not included on the list of prohibited medications
  • Unable to swallow capsules or malabsorption syndrome, active disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction resulting in malabsorption or chronic diarrhea
  • Active abuse of alcohol

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: SAVE (Safe Accelerated Venetoclax Escalation): A Phase Ib Study of Venetoclax Monotherapy With Accelerated Dose Ramp-up in Patients With CLL

This research study is trying to determine which patients with newly diagnosed or relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), as grouped by their risk for tumor lysis syndrome (TLS), are able to safely tolerate an accelerated, daily venetoclax dose ramp-up rather than the standard approved schedule (5-week dose ramp-up).

The name of the study drug involved in this study is:

  • Venetoclax

The following drugs may also be included in some participants treatment regimen:

  • Obinutuzumab
  • Rituximab
Read the detailed description

This is an open label phase Ib study of an accelerated venetoclax ramp-up in patients with CLL/SLL in either the front-line or relapsed/refractory setting. This clinical trial is testing a new dosing schedule of a drug that is normally dosed in a different fashion. As such, venetoclax is considered an investigational drug when given in this new schedule. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has approved venetoclax as a treatment option for CLL or SLL but the approval is based on a different schedule.

Venetoclax is an oral drug inhibitor of BCL-2, a protein that regulates the death of cells in the body. It has been FDA approved with or without rituximab for the treatment of adult patients with CLL/SLL who have received at least one prior therapy, with obinutuzumab for frontline therapy of CLL/SLL, as well in combination with azacitabine, decitabine, or low-dose cytarabine for the treatment of adults with newly diagnosed acute myeloid leukemia (AML).

Venetoclax is typically started at a low dose and increased on a weekly basis, over 5 weeks, to the desired dose for patients with CLL/SLL.This study is trying to determine if patients can safely increase the venetoclax dose in the hospital on a daily basis, over 5 days rather than weekly, and which patients, grouped by their risk for TLS, with newly diagnosed or relapsed/refractory CLL/SLL, are able to safely tolerate this accelerated, daily venetoclax dose ramp-up.

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

All participants will be actively followed for approximately 3 months. Following completion of the active study period, participants will be encouraged to return for a response evaluation. Following this, patients will enter a long-term follow up period where they will be observed for a maximum of 5 years.

It is expected that about 40 people will take part in this research study.

Keywords
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Medical subject headings
Leukemia, Lymphocytic, Chronic, 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

  • ObinutuzumabDrug

    Also called Gazyva

    Given as an infusion into the vein (intravenous, IV).

  • RituximabDrug

    Also called Rituxan

    Given as an infusion into the vein (intravenous, IV).

Study groups in NCT04843904
Study groupRoleWhat they receive
VenetoclaxExperimentalParticipants will be separated into two cohorts: Cohort A: Patients at low risk for TLS. Cohort B: Patients with both median and high risk for TLS. Five (5) participants from cohort A will be initially enrolled, if these first 5 participants tolerate the accelerated ramp-up, cohorts A and B will enroll simultaneously. All participants will be hospitalized and receive venetoclax daily with accelerated dose increases over 5 days to reach full dose. After reaching full dose, participants will be discharged and continue daily venetoclax at home. Per doctor assessment, some participants may also receive rituximab or obinutuzumab as part of the treatment regimen with venetoclax. Rituximab: Given every 28 days starting on the second study cycle and continuing for up to 6 cycles as per standard of care. Obinutuzumab: Days 1, 2, 8, and 15 of cycle 1 and once every 28 days there after for up to 6 cycles as per standard of care.
Receives: Drug: Venetoclax; Drug: Obinutuzumab; Drug: Rituximab

What is being measured

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

  1. Highest risk TLS group that can safely tolerate the daily ramp up

    Rates of laboratory and clinical TLS

    Measured: 3 months

Secondary outcomes (5)

  1. Objective response rate (ORR)

    Evaluated using the 2018 iwCLL criteria for CLL

    Measured: 3 months

  2. Complete response (CR) rate

    Evaluated using the 2018 iwCLL criteria for CLL

    Measured: 3 months

  3. Progression free survival (PFS)

    Time to progression or death

    Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years

  4. Overall survival (OS)

    Death due to any cause

    Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years

  5. Rate of undetectable minimal residual disease (uMRD)

    Determined by flow cytometry and ClonoSeq

    Measured: 3 months

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 start14 Apr 2021
  3. Primary completion2 Jun 2025
  4. Study completion2 Jun 2030 (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
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04843904
Sponsor's protocol ID
20-415
Acronym
SAVE
Status last verified
Jan 2026
First submitted
30 Mar 2021
Last updated
7 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

  • Crombie JL, Ahn IE, Ren Y, Tyekucheva S, Carey C, Kniezewski M, Normilus S, Solomon S, Montegaard J, Kim AI, Merryman RW, Armand P, Fisher DC, Brown JR, Davids MS. SAVE, Safe Accelerated Venetoclax Escalation: A phase Ib study of obinutuzumab plus venetoclax with daily ramp-up in CLL. Blood Adv. 2026 Jun 23:bloodadvances.2026020392. doi: 10.1182/bloodadvances.2026020392. Online ahead of print.

    PubMed 42335220

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax, Obinutuzumab and Rituximab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Dana-Farber Cancer Institute 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 20 inclusion and 20 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 7 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 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?

Highest risk TLS group that can safely tolerate the daily ramp up (time frame: 3 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 NCT04843904, 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 7 Jan 2026.

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