Ibrutinib (PCI-32765) in Waldenstrom's Macroglobulinemia
Study Details
Study Description
Brief Summary
This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug, PCI-32765, to learn whether PCI-32765 works in treating a specific cancer. "Investigational" means that PCI-32765 is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if PCI-32765 is effective for treating different types of cancer. It also means that the FDA has not yet approved PCI-32765 for use in patients, including people with Waldenstrom's Macroglobulinemia.
PCI-32765 is a newly discovered drug that is being developed as an anti-cancer agent. PCI-32765 is a Bruton's tyrosine kinase (Btk) inhibitor drug which interrupts B cell receptor (BCR) signaling in lymphomas by selectively and irreversibly binding to the Btk protein, which then results in malignant cell death. This drug has been used in laboratory experiments and other research studies in B-cell malignancies and information from those other research studies suggests that PCI-32765 may be a treatment strategy for B-cell malignancies, including Waldenstrom's Macroglobulinemia.
In this research study, the investigators are testing the safety and efficacy of PCI-32765 as a treatment option for relapsed or refractory Waldenstrom's Macroglobulinemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Patients in this research study will receive up to 40 cycles of treatment. Each treatment cycle lasts 4 weeks. Patients will take PCI-32765 by mouth, once a day in the morning.
During each cycle patients will be asked to visit the clinic for scheduled tests and exams and to receive a supply of PCI-32765 to take at home every day. Patients will visit the clinic on the first day of each of the first 3 cycles, and then just once at the beginning of every three cycles.
During study visits, patients will have a physical exam where they will be asked questions about their general health and specific questions about any problems that they might be having and any medications they may be taking. Patients will have blood tests to see how their disease is responding to the study treatment and how they are tolerating the study drug. Patients may also have CT scans of the chest, abdomen and pelvis as well as a bone marrow aspirate and biopsy. If a patient's disease stays the same or is helped, he/she will continue to get study treatment. If disease worsens, he/she will be taken off study treatment at that time.
After completion of the treatment and as part of standard of care, follow-up tests will include a physical exam, review of symptoms and medications, blood tests, bone marrow aspirate and biopsy, CT scans of the chest, abdomen and pelvis. The investigators would like to continue to monitor progress by following-up every three months for up to two years after completion of study treatment or until next treatment, whichever comes first.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Arm PCI-32765; ibrutinib |
Drug: PCI-32765
Taken orally, once daily in the morning
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate [4 years]
To assess the overall response rate (>25% reduction in serum IgM from baseline).
Secondary Outcome Measures
- Safety and Tolerability of PCI-32765 [4 years]
To assess the safety and tolerability of PCI-32765 in symptomatic WM patients with relapsed/refractory disease. Grade > or = 2 Adverse Events determined to be associated with PCI-32765 and subsequent outcomes will constitute the safety profile of PCI-32765 in WM. Percent of participants who experienced at least 1 grade 2 or higher treatment emergent adverse event.
- Determine Progression Free Survival [6 years]
To determine Progression Free Survival (PFS in symptomatic WM patients with relapsed/refractory disease. Participants were treated for 40 cycles and then followed for 2 years or until next therapy or death. 40 participants were censored prior to disease progression.
- To Determine Time to Next Therapy (TTNT) of PCI-32765 in Symptomatic WM Patients With Relapsed/Refractory Disease [6 years]
Time to Next Therapy is the duration of time from of starting ibrutinib until next therapy. Participants were treated for 40 cycles and then followed for 2 years or until next therapy or death. Participants had the option to continue ibrutinib commercially. 40 participants were censored while still on commercial ibrutinib therapy.
- Major Response Rates [4 years]
To assess the major response rate (>50% reduction in serum IgM from baseline)
- Very Good Partial Response Rate [4 years]
To assess the very good partial response rate (>90% reduction in serum IgM from baseline)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Clinicopathological diagnosis of Waldenstrom's Macroglobulinemia
-
Measurable disease
-
Have received at least one prior therapy for WM therapies
-
Disease free of prior malignancies
-
Able to adhere to study visit schedule and other protocol requirement
Exclusion Criteria:
-
Pregnant or breastfeeding
-
Any other serious medical condition
-
Concurrent use of other anti-cancer agents or treatments
-
Prior exposure to PCI-32765
-
Known CNS lymphoma
-
Significant cardiovascular disease
-
Any disease affecting gastrointestinal function
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford University | Palo Alto | California | United States | 94305 |
| 2 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02215 |
| 3 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 4 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Dana-Farber Cancer Institute
Investigators
- Principal Investigator: Steven P Treon, MD PhD, Dana-Farber Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 12-015
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning |
| Period Title: Overall Study | |
| STARTED | 63 |
| COMPLETED | 63 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning |
| Overall Participants | 63 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
32
50.8%
|
| >=65 years |
31
49.2%
|
| Age (years) [Median (Standard Deviation) ] | |
| Median (Standard Deviation) [years] |
63
(10.6)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
15
23.8%
|
| Male |
48
76.2%
|
| Race and Ethnicity Not Collected (Count of Participants) | |
| Region of Enrollment (participants) [Number] | |
| United States |
63
100%
|
Outcome Measures
| Title | Overall Response Rate |
|---|---|
| Description | To assess the overall response rate (>25% reduction in serum IgM from baseline). |
| Time Frame | 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning |
| Measure Participants | 63 |
| Count of Participants [Participants] |
57
90.5%
|
| Title | Safety and Tolerability of PCI-32765 |
|---|---|
| Description | To assess the safety and tolerability of PCI-32765 in symptomatic WM patients with relapsed/refractory disease. Grade > or = 2 Adverse Events determined to be associated with PCI-32765 and subsequent outcomes will constitute the safety profile of PCI-32765 in WM. Percent of participants who experienced at least 1 grade 2 or higher treatment emergent adverse event. |
| Time Frame | 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning |
| Measure Participants | 63 |
| Count of Participants [Participants] |
62
98.4%
|
| Title | Determine Progression Free Survival |
|---|---|
| Description | To determine Progression Free Survival (PFS in symptomatic WM patients with relapsed/refractory disease. Participants were treated for 40 cycles and then followed for 2 years or until next therapy or death. 40 participants were censored prior to disease progression. |
| Time Frame | 6 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning |
| Measure Participants | 63 |
| Median (Full Range) [months] |
39
|
| Title | To Determine Time to Next Therapy (TTNT) of PCI-32765 in Symptomatic WM Patients With Relapsed/Refractory Disease |
|---|---|
| Description | Time to Next Therapy is the duration of time from of starting ibrutinib until next therapy. Participants were treated for 40 cycles and then followed for 2 years or until next therapy or death. Participants had the option to continue ibrutinib commercially. 40 participants were censored while still on commercial ibrutinib therapy. |
| Time Frame | 6 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning |
| Measure Participants | 63 |
| Median (Full Range) [months] |
49
|
| Title | Major Response Rates |
|---|---|
| Description | To assess the major response rate (>50% reduction in serum IgM from baseline) |
| Time Frame | 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning |
| Measure Participants | 63 |
| Count of Participants [Participants] |
49
77.8%
|
| Title | Very Good Partial Response Rate |
|---|---|
| Description | To assess the very good partial response rate (>90% reduction in serum IgM from baseline) |
| Time Frame | 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning |
| Measure Participants | 63 |
| Count of Participants [Participants] |
17
27%
|
Adverse Events
| Time Frame | Adverse events were collected from Cycle 1 Day 1 through 30 days after discontinuing protocol ibrutinib therapy, an average of 3 years. | |
|---|---|---|
| Adverse Event Reporting Description | Grade 2 and above treatment emergent adverse events were collected. | |
| Arm/Group Title | Treatment Arm | |
| Arm/Group Description | PCI-32765; ibrutinib PCI-32765: Taken orally, once daily in the morning | |
All Cause Mortality |
||
| Treatment Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/63 (1.6%) | |
Serious Adverse Events |
||
| Treatment Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 30/63 (47.6%) | |
| Blood and lymphatic system disorders | ||
| Neutropenic Fever and Chills | 1/63 (1.6%) | 1 |
| Anemia | 2/63 (3.2%) | 2 |
| Cardiac disorders | ||
| Atrial Fibrillation | 2/63 (3.2%) | 2 |
| Pericarditis | 1/63 (1.6%) | 1 |
| General disorders | ||
| Fever and Tachycardia | 1/63 (1.6%) | 1 |
| Malaise | 1/63 (1.6%) | 1 |
| Fever | 3/63 (4.8%) | 3 |
| Hepatobiliary disorders | ||
| Cholecystitis | 1/63 (1.6%) | 1 |
| Infections and infestations | ||
| Flu | 1/63 (1.6%) | 1 |
| Cellulitis | 1/63 (1.6%) | 1 |
| Pneumonia | 11/63 (17.5%) | 11 |
| Endocarditis | 1/63 (1.6%) | 1 |
| Herpes Zoster | 1/63 (1.6%) | 1 |
| Upper Respiratory Infection | 1/63 (1.6%) | 1 |
| Group A Streptococcus | 1/63 (1.6%) | 1 |
| Foot Infection | 1/63 (1.6%) | 1 |
| Kidney Infection | 1/63 (1.6%) | 1 |
| Injury, poisoning and procedural complications | ||
| Femur Fracture | 1/63 (1.6%) | 1 |
| Investigations | ||
| Platelet Count Decreased | 2/63 (3.2%) | 2 |
| Neutrophil count Decreased | 1/63 (1.6%) | 1 |
| Metabolism and nutrition disorders | ||
| Dehydration | 1/63 (1.6%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Disease Transformation DLBCL | 2/63 (3.2%) | 2 |
| Myelodysplastic Syndrome | 1/63 (1.6%) | 1 |
| Adenocarcinoma of the rectum | 1/63 (1.6%) | 1 |
| Squamous cell carcinoma | 2/63 (3.2%) | 2 |
| Prostate Cancer | 1/63 (1.6%) | 1 |
| Nervous system disorders | ||
| Syncope | 1/63 (1.6%) | 1 |
| Psychiatric disorders | ||
| Depression and Suicidal Ideation | 1/63 (1.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Pleural effusion | 2/63 (3.2%) | 2 |
| Vascular disorders | ||
| Hematoma | 1/63 (1.6%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Treatment Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 62/63 (98.4%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 40/63 (63.5%) | 40 |
| Febrile Neutropenia | 2/63 (3.2%) | 2 |
| Leukocytosis | 1/63 (1.6%) | 1 |
| Cardiac disorders | ||
| Atrial Fibrillation | 9/63 (14.3%) | 9 |
| Palpiatations | 3/63 (4.8%) | 3 |
| Sick sinus syndrome | 1/63 (1.6%) | 1 |
| Sinus bradycardia | 2/63 (3.2%) | 2 |
| Sinus tachycardia | 2/63 (3.2%) | 2 |
| Ventricular arrhythmia | 1/63 (1.6%) | 1 |
| Ear and labyrinth disorders | ||
| Hearing impaired | 1/63 (1.6%) | 1 |
| Tinnitis | 2/63 (3.2%) | 2 |
| Endocrine disorders | ||
| Hypothyroidism | 1/63 (1.6%) | 1 |
| Eye disorders | ||
| Blurred vision | 7/63 (11.1%) | 7 |
| Cataract | 1/63 (1.6%) | 1 |
| Conjunctivitis | 1/63 (1.6%) | 1 |
| Eye pain | 2/63 (3.2%) | 2 |
| Retinal detachment | 2/63 (3.2%) | 2 |
| Retinal tear | 1/63 (1.6%) | 1 |
| Watering eyes | 1/63 (1.6%) | 1 |
| Gastrointestinal disorders | ||
| Abdominal Pain | 7/63 (11.1%) | 7 |
| Bloating | 3/63 (4.8%) | 3 |
| Constipation | 8/63 (12.7%) | 8 |
| Diarrhea | 20/63 (31.7%) | 20 |
| Duodenal ulcer | 1/63 (1.6%) | 1 |
| Dyspepsia | 1/63 (1.6%) | 1 |
| Dysphagia | 3/63 (4.8%) | 3 |
| Gastric ulcer | 1/63 (1.6%) | 1 |
| Gastroesophageal reflux disease | 12/63 (19%) | 12 |
| Hemorrhoidal hemmorhage | 1/63 (1.6%) | 1 |
| Hemorrhoids | 1/63 (1.6%) | 1 |
| Oral Mucositis | 8/63 (12.7%) | 8 |
| Nausea | 9/63 (14.3%) | 9 |
| Oral hemorrhage | 4/63 (6.3%) | 4 |
| Proctitis | 1/63 (1.6%) | 1 |
| Rectal perforation | 1/63 (1.6%) | 1 |
| Small intestinal obstruction | 1/63 (1.6%) | 1 |
| Toothache | 1/63 (1.6%) | 1 |
| Vomiting | 7/63 (11.1%) | 7 |
| General disorders | ||
| Chills | 3/63 (4.8%) | 3 |
| Facial edema | 1/63 (1.6%) | 1 |
| Edema limbs | 9/63 (14.3%) | 9 |
| Fatigue | 33/63 (52.4%) | 33 |
| Fever | 13/63 (20.6%) | 13 |
| Fly-like symptoms | 4/63 (6.3%) | 4 |
| Malaise | 6/63 (9.5%) | 6 |
| Non-cardiac chest pain | 2/63 (3.2%) | 2 |
| Pain | 7/63 (11.1%) | 7 |
| Infections and infestations | ||
| Bladder Infection | 3/63 (4.8%) | 3 |
| Bronchial infection | 7/63 (11.1%) | |
| Eye infection | 1/63 (1.6%) | 1 |
| Gum infection | 1/63 (1.6%) | 1 |
| Lip infection | 1/63 (1.6%) | 1 |
| Lung infection | 14/63 (22.2%) | 14 |
| Mucosal infection | 3/63 (4.8%) | 3 |
| Nail infection | 3/63 (4.8%) | 3 |
| Otitis media | 3/63 (4.8%) | 3 |
| Penile Infection | 1/63 (1.6%) | 1 |
| Pharyngitis | 1/63 (1.6%) | 1 |
| Sinusitis | 21/63 (33.3%) | 21 |
| Skin infection | 11/63 (17.5%) | 11 |
| Soft tissue infection | 1/63 (1.6%) | 1 |
| Tooth infection | 1/63 (1.6%) | 1 |
| Upper respiratory infection | 19/63 (30.2%) | 19 |
| Urinary tract infection | 9/63 (14.3%) | 9 |
| Vaginal infection | 1/63 (1.6%) | 1 |
| Wound infection | 1/63 (1.6%) | 1 |
| Injury, poisoning and procedural complications | ||
| Bruising | 8/63 (12.7%) | 8 |
| Fall | 2/63 (3.2%) | 2 |
| Fracture | 4/63 (6.3%) | 4 |
| Wound complication | 2/63 (3.2%) | 2 |
| Investigations | ||
| Alanine aminotransferase increased | 2/63 (3.2%) | 2 |
| Alkaline phosphatase increased | 2/63 (3.2%) | 2 |
| Aspartate aminotransferase increased | 2/63 (3.2%) | 2 |
| Blood bilirubin increased | 4/63 (6.3%) | 4 |
| Creatinine increased | 1/63 (1.6%) | 1 |
| Lipase increased | 2/63 (3.2%) | 2 |
| Neutrophil count decreased | 26/63 (41.3%) | 26 |
| Platelet count decreased | 29/63 (46%) | 29 |
| Weight gain | 2/63 (3.2%) | 2 |
| Weight loss | 4/63 (6.3%) | 4 |
| White blood cell decreased | 2/63 (3.2%) | 2 |
| Metabolism and nutrition disorders | ||
| Anorexia | 2/63 (3.2%) | 2 |
| Dehydration | 4/63 (6.3%) | 4 |
| Hypercalcemia | 1/63 (1.6%) | 1 |
| Hyperglycemia | 1/63 (1.6%) | 1 |
| Hypoalbuminemia | 5/63 (7.9%) | 5 |
| Hypoglycemia | 1/63 (1.6%) | 1 |
| Hypokalemia | 4/63 (6.3%) | 4 |
| Hypomagnesemia | 1/63 (1.6%) | 1 |
| Hyponatremia | 2/63 (3.2%) | 2 |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 17/63 (27%) | 17 |
| Back pain | 5/63 (7.9%) | 5 |
| Bone pain | 3/63 (4.8%) | 3 |
| Chest wall pain | 1/63 (1.6%) | 1 |
| Muscle weakness lower limb | 1/63 (1.6%) | 1 |
| Myalgia | 14/63 (22.2%) | 14 |
| Neck Pain | 1/63 (1.6%) | 1 |
| Pain in extremity | 2/63 (3.2%) | 2 |
| Nervous system disorders | ||
| Dizziness | 11/63 (17.5%) | 11 |
| Dysgeusia | 1/63 (1.6%) | 1 |
| Headache | 11/63 (17.5%) | 11 |
| Paresthesia | 7/63 (11.1%) | 7 |
| Peripheral motor neuropathy | 9/63 (14.3%) | 9 |
| Peripheral sensory neuropathy | 12/63 (19%) | 12 |
| Stroke | 1/63 (1.6%) | 1 |
| Syncope | 1/63 (1.6%) | 1 |
| Psychiatric disorders | ||
| Anxiety | 6/63 (9.5%) | 6 |
| Depression | 4/63 (6.3%) | 4 |
| Insomnia | 5/63 (7.9%) | 5 |
| Renal and urinary disorders | ||
| Acute kidney injury | 1/63 (1.6%) | 1 |
| Hematuria | 4/63 (6.3%) | 4 |
| Renal calculi | 2/63 (3.2%) | 2 |
| urinary tract obstruction | 2/63 (3.2%) | 2 |
| Urinary tract pain | 1/63 (1.6%) | 1 |
| Urinary urgency | 2/63 (3.2%) | 2 |
| Reproductive system and breast disorders | ||
| Irregular menstruation | 1/63 (1.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Allergic rhinitis | 1/63 (1.6%) | 1 |
| Cough | 11/63 (17.5%) | 11 |
| Dyspnea | 6/63 (9.5%) | 6 |
| Epistaxis | 8/63 (12.7%) | 8 |
| Hypoxia | 1/63 (1.6%) | 1 |
| Nasal congestion | 3/63 (4.8%) | 3 |
| Pleural effusion | 10/63 (15.9%) | 10 |
| Pneumonitis | 1/63 (1.6%) | 1 |
| Postnasal drip | 1/63 (1.6%) | 1 |
| Productive cough | 1/63 (1.6%) | 1 |
| Respiratory failure | 1/63 (1.6%) | 1 |
| Sore throat | 2/63 (3.2%) | 2 |
| Wheezing | 2/63 (3.2%) | 2 |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 1/63 (1.6%) | 1 |
| Dry eye | 1/63 (1.6%) | 1 |
| Nail ridging | 7/63 (11.1%) | 7 |
| Pruritis | 5/63 (7.9%) | 5 |
| Purpura | 1/63 (1.6%) | 1 |
| Rash acneiform | 3/63 (4.8%) | 3 |
| Rash maculo-papular | 7/63 (11.1%) | 7 |
| scalp pain | 1/63 (1.6%) | 1 |
| Skin hyperpigmentation | 1/63 (1.6%) | 1 |
| Urticaria | 1/63 (1.6%) | 1 |
| Vascular disorders | ||
| Hematoma | 5/63 (7.9%) | 5 |
| Hot flashes | 1/63 (1.6%) | 1 |
| Hypertension | 9/63 (14.3%) | 9 |
| Hypotension | 2/63 (3.2%) | 2 |
| Lymphedema | 1/63 (1.6%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Steven Treon |
|---|---|
| Organization | Dana-Farber Cancer Institute |
| Phone | 617-632-2681 |
| steven_treon@dfci.harvard.edu |
- 12-015