Clinical trial NCT02677324: Study of ABT-199 (GDC-199) In Patients With Relapsed Or Refractory Waldenström Macroglobulinemia
Official title: Phase II Study of ABT-199 (GDC-199) In Patients With Relapsed Or Refractory Waldenström Macroglobulinemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Waldenstrom Macroglobulinemia
Keywords: Waldenstrom Macroglobulinemia
WM
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: AbbVie
First posted: 2016-02-09
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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:

  * 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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Overall Response Rate
timeFrame: 2 years
Secondary outcomes:
measure: Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
timeFrame: 2 years
measure: Number of Participants With Complete Response
timeFrame: 2 years
measure: Number of Participants With Very Good Partial Response
timeFrame: 2 years
measure: Number of Participants With Partial Response
timeFrame: 2 years
measure: Number of Participants With Minor Response
timeFrame: 2 years
measure: Number of Participants With Stable Disease
timeFrame: 2 years
measure: Progression Free Survival
timeFrame: 4 years
measure: Overall Response Rate Among CXCR4 Mutated Participants
timeFrame: 2 years
measure: Overall Response Rate Among Participants Without CXCR4 Mutations
timeFrame: 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Jorge J Castillo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.