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Waldenstrom MacroglobulinemiaPhase 2NCT02677324

Study of ABT-199 (GDC-199) In Patients With Relapsed Or Refractory Waldenström Macroglobulinemia

A Phase 2 study testing ABT199 in people with Waldenstrom Macroglobulinemia, run by Dana-Farber Cancer Institute at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This research study is studying a targeted therapy as a possible treatment for relapsed or refractory Waldenstrom's Macroglobulinemia (WM). This study is using the study intervention ABT-199. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Waldenstrom Macroglobulinemia
What is being tested?
ABT199
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
4 sitesUnited States
Study dates
9 May 2016to 7 Feb 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Clinicopathological diagnosis of Waldenstrom's Macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom's macroglobulinemia (Owen 2003; Kyle 2003).
  • Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of > 2 times the upper limit of normal of each institution is required.
  • Have received at least one prior therapy for WM.
  • Age ≥ 18 years.
  • ECOG performance status <2 (see Appendix A).
  • Participants must have normal organ and marrow function (growth factors cannot be given prophylactically to establish eligibility) as defined below:
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  • Absolute neutrophil count > 1,000/mm3
  • Platelets > 50,000/mm3
  • Hemoglobin > 8 g/dL
  • Total bilirubin ≤ 1.5 mg/dL or < 2 mg/dL if attributable to hepatic infiltration by neoplastic disease
  • AST (SGOT) and ALT (SGPT) < 2.5X the institutional upper limit of normal
  • Creatinine clearance ≥50 ml/min
  • Not on any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin.
  • Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or have or will have complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) while participating in the study; and 2) for at least 28 days after discontinuation from the study. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. FCBP must be referred to a qualified provider of contraceptive methods if needed.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent the participant from signing the informed consent form.
  • Concurrent use of any other anti-cancer agents or treatments or any other study agents.
  • Prior exposure to ABT-199 or BCL2 inhibitors.
  • Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the patient, including symptomatic hyperviscosity; alter the absorption, distribution, metabolism or excretion of ABT-199; or impair the assessment of study results.
  • Grade > 2 toxicity (other than alopecia) continuing from prior anti-cancer therapy.
  • Known CNS lymphoma.
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  • Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening.
  • New York Heart Association classification III or IV heart failure.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
  • Known history of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV) infection.
  • Lactating or pregnant women.
  • Inability to swallow tablets.
  • History of non-compliance to medical regimens.
  • Unwilling or unable to comply with the protocol.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Weill Cornell Medical College

    New York, New York, 10065

  • Stanford University

    Palo Alto, California, 94304

Other trials in United States

About this study

Official title: Phase II Study of ABT-199 (GDC-199) In Patients With Relapsed Or Refractory Waldenström Macroglobulinemia

This research study is studying a targeted therapy as a possible treatment for relapsed or refractory Waldenstrom's Macroglobulinemia (WM). This study is using the study intervention ABT-199.

Read the detailed description

This research study is a Phase II clinical trial. ABT-199 is a pill that blocks BCL-2, a protein that is important for the survival of WM cells.

The purpose of this research study is to evaluate how well the study drug works and the safety of ABT-199 as a single agent in participants with WM that has come back or has shown no response to previous treatment.

The FDA (the U.S. Food and Drug Administration) has not approved ABT-199 as a treatment for any disease.

Being tested
ABT199
Keywords
Waldenstrom Macroglobulinemia, WM
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

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

  • ABT199Drug

    Also called Venetoclax

    Oral BCL-2 antagonist

Study groups in NCT02677324
Study groupRoleWhat they receive
ABT199ExperimentalABT199 will be administered daily, with 28 consecutive days defined as a treatment cycle for a maximum for 26 cycles
Receives: Drug: ABT199

What is being measured

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

  1. Overall Response Rate

    Overall Response Rate= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

    Measured: 2 years

Secondary outcomes (9)

  1. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

    Number of participants who experienced an adverse event while on ABT-199

    Measured: 2 years

  2. Number of Participants With Complete Response

    A complete response is defined as having resolution of WM related symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly.

    Measured: 2 years

  3. Number of Participants With Very Good Partial Response

    Very Good Partial Response (VGPR): is defined as ≥90% reduction in serum IgM levels, or normalization of serum IgM levels.

    Measured: 2 years

  4. Number of Participants With Partial Response

    Partial response (PR) is defined as achieving a ≥50% reduction in serum IgM levels.

    Measured: 2 years

  5. Number of Participants With Minor Response

    Minor Response (MR): A minor response (MR) is defined 25-49% reduction in serum IgM levels.

    Measured: 2 years

  6. Number of Participants With Stable Disease

    Stable disease is defined as having <25% increase in serum IgM levels and <25% reduction in serum IgM levels

    Measured: 2 years

  7. Progression Free Survival

    Amount of time following ABT-199 administration until >25% increase in serum IgM

    Measured: 4 years

  8. Overall Response Rate Among CXCR4 Mutated Participants

    Overall Response Rate for participants who tested positive for a CXCR4 mutation= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

    Measured: 2 years

  9. Overall Response Rate Among Participants Without CXCR4 Mutations

    Overall Response Rate in participants who tested negative for a CXCR4 mutation= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

    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 posted9 Feb 2016 (estimated)
  2. Study start9 May 2016
  3. Primary completion14 Feb 2020
  4. Study completion7 Feb 2022

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02677324
Sponsor's protocol ID
15-491
Other IDs
A15-751
Status last verified
Apr 2022
First submitted
14 Jan 2016
Last updated
11 May 2022
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Castillo JJ, Guijosa A, Allan JN, Siddiqi T, Advani RH, Flynn CA, Meid K, Budano N, Nguyen J, Ramirez-Gamero A, Tsakmaklis N, Hunter ZR, Patterson CJ, Treon SP, Sarosiek S. Long-term follow-up of venetoclax monotherapy in previously treated patients with Waldenstrom macroglobulinemia. Blood Adv. 2025 Oct 14;9(19):4842-4847. doi: 10.1182/bloodadvances.2025016890.

    PubMed 40674749

  • Castillo JJ, Allan JN, Siddiqi T, Advani RH, Meid K, Leventoff C, White TP, Flynn CA, Sarosiek S, Branagan AR, Demos MG, Guerrera ML, Kofides A, Liu X, Munshi M, Tsakmaklis N, Xu L, Yang G, Patterson CJ, Hunter ZR, Davids MS, Furman RR, Treon SP. Venetoclax in Previously Treated Waldenstrom Macroglobulinemia. J Clin Oncol. 2022 Jan 1;40(1):63-71. doi: 10.1200/JCO.21.01194. Epub 2021 Nov 18.

    PubMed 34793256

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ABT199 in people with Waldenstrom Macroglobulinemia, run by Dana-Farber Cancer Institute at 4 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 16 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: finished, as of the sponsor's last update on 11 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 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?

Yes. Results are posted in the registry (first posted 11 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Response Rate (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 NCT02677324, which also lists 2 linked publications.

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 11 May 2022.

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