Waldenstrom's Macroglobulinemia
Conditions
Keywords
Waldenstrom's Macroglobulinemia
Brief summary
This research study is studying a drug called ibrutinib as a possible treatment for untreated Waldenstrom's Macroglobulinemia (WM).
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. Investigational means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has approved ibrutinib as a form of treatment for the patient specific disease. Ibrutinib has been under investigation in research studies in participants with recurrent B-cell lymphoma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and prolymphocytic leukemia, and WM. In a study of ibrutinib in relapsed/refractory WM patients, response rates were high and the treatment was well tolerated. The prior studies suggest that ibrutinib may be a useful treatment strategy for untreated WM patients. This study will test the safety and efficacy of ibrutinib as an option for untreated WM patients. The study will also conduct genomic sequencing of malignant WM cells before the start of treatment, and 6, 12, 24, 36 and 48 months afterwards. Genomic sequencing is the analysis of the entire DNA structure from tumor and normal cells. The purpose of this sequencing is to study which genetic changes effect how ibrutinib works. The results of these studies could also help in better understanding the course of WM disease, and be applicable to the development of other effective drug treatments.
Interventions
DRUGIbrutinib
Sponsors
Pharmacyclics LLC.
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 (Kyle et al, 2003). * Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of ≥ 2 times the upper limit of normal is required. * Age ≥ 18 years. * Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (see Appendix A.). * Participants must have normal organ and marrow function as defined below: * Absolute neutrophil count ≥ 1,000/μL * Platelets ≥ 50,000/μL * Hemoglobin ≥ 8 g/dL * Total bilirubin ≤ 2.0. mg/dL or \< 2.5 mg/dL if attributable to hepatic infiltration by neoplastic disease or Gilbert's syndrome. * Aspartate aminotransferase (AST or SGOT) and Alanine aminotransferase (ALT or SGPT) ≤ 2.5 X institutional upper limit of normal * Estimated Creatinine Clearance ≥30ml/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. * Both men and women of all races and ethnic groups are eligible for this trial.
Exclusion criteria
* Prior systemic therapy for WM * 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 treatments or any other investigational agents. * Concomitant use of warfarin or other Vitamin K antagonists. * Concomitant treatment with strong CYP3A4/5 inhibitor. * Any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion could interfere with the absorption or metabolism of ibrutinib. * Known Central nervous system (CNS) lymphoma. * Concomitant use of medication known to cause QT prolongation. * Currently active, clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction, unstable angina or acute coronary syndrome within 6 months of screening. * Malabsorption, 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), active infection with Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV). Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded. * Lactating or pregnant women. * Inability to swallow capsules. * History of non-compliance to medical regimens. * Unwilling or unable to comply with the protocol. * Major surgery within 4 weeks of first dose of study drug. * No active infections requiring systemic therapy. * Known bleeding disorders with the exception of acquired Von Willebrand Disorder suspected on the basis of WM. * History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Response Rate | 4 years | To asses the percentage of participants with a Partial Response (PR) (50% reduction or more in serum IgM) or better. |
| Best Overall Response Rate | 4 years | To asses the percentage of participants with an Minor Response (MR) (25% reduction or more in serum IgM) or better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | 6 years | The amount of time between attainment of at least a minor response and disease progression. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to Response | 4 years | The amount of time between starting treatment and attaining at least a minor response to therapy |
| Progression Free Survival | 6 years | The number of participants who have not experienced disease progression 6 years after therapy initiation |
| Overall Survival | 6 years | The number of participants who are still living 6 years after initiation of ibrutinib |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ibrutinib This is single arm, open label, Phase II, single center study designed to evaluate the safety and efficacy of ibrutinib in previously untreated WM patients. Treatment will be administered in 4-week cycles, and participants will receive treatment for up to 48 cycles. Treatment will be comprised of ibrutinib at 420 mg per day by oral administration.
Ibrutinib | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Disease Progression | 4 |
| Overall Study | Intercurrent illness | 1 |
| Overall Study | Participant ineligible | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Ibrutinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 20 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 67 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 31 |
| other Total, other adverse events | 31 / 31 |
| serious Total, serious adverse events | 15 / 31 |
Outcome results
Primary
Best Overall Response Rate
To asses the percentage of participants with an Minor Response (MR) (25% reduction or more in serum IgM) or better.
Time frame: 4 years
Population: All participants except one participant determined to be ineligible
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ibrutinib | Best Overall Response Rate | 30 Participants |
Primary
Major Response Rate
To asses the percentage of participants with a Partial Response (PR) (50% reduction or more in serum IgM) or better.
Time frame: 4 years
Population: All participants except one participant determined to be ineligible
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ibrutinib | Major Response Rate | 26 Participants |
Secondary
Duration of Response
The amount of time between attainment of at least a minor response and disease progression.
Time frame: 6 years
Population: All participants except one determined to be ineligible
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ibrutinib | Duration of Response | 46 months |
Other Pre-specified
Overall Survival
The number of participants who are still living 6 years after initiation of ibrutinib
Time frame: 6 years
Population: All participants except one who was determined to be ineligible
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ibrutinib | Overall Survival | 30 Participants |
Other Pre-specified
Progression Free Survival
The number of participants who have not experienced disease progression 6 years after therapy initiation
Time frame: 6 years
Population: All participants except for one determined to be ineligible
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ibrutinib | Progression Free Survival | 24 Participants |
Other Pre-specified
Time to Response
The amount of time between starting treatment and attaining at least a minor response to therapy
Time frame: 4 years
Population: All participants except one determined to be ineligible
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ibrutinib | Time to Response | 0.9 months |