Richter Syndrome
Conditions
Keywords
leukemia, richter
Brief summary
This research study studies the combination of ibrutinib and obinutuzumab with or without the standard chemotherapy regimen of CHOP to see how well these drugs work in treating patients with a diagnosis of Richter's Transformation or Richter's Syndrome. The Bruton's Tyrosine Kinase (BTK) inhibitor, ibrutinib, may stop growth of cancer cells by blocking the signal needed for cell growth. The monoclonal antibody obinutuzumab may block cancer growth by targeting cells present in Richter's Transformation. Giving ibrutinib with obinutuzumab may be a better treatment for patients with Richter's Transformation. Depending on fitness, the patients may receive ibrutinib and obinutuzumab in combination with a regimen known as CHOP (C= cyclophosphamide, H= hydroxydaunorubicin (also called doxorubicin), O= oncovin (also called vincristine, and P= prednisolone or prednisone (corticosteroids).
Interventions
DRUGObinutuzumab
100 mg on day 1 and 900 mg on day 2 Cycle 1, 1000 mg on day 8 and 15 of Cycle 1, and 1000 mg on day 1 of Cycles 2-6
DRUGIbrutinib
560mg po daily
OTHERCHOP
cyclophosphamide, doxorubicin, vincristine, and prednisone
Sponsors
Pharmacyclics LLC.
Northwell Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
parallel assignment based on fitness of participants
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* confirmed Richter's transformation in treatment naïve and previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma patients * may have had prior exposure to ibrutinib and other B-cell signaling receptor agents * Adequate hematologic function * Adequate liver and kidney function * Willing and able to participate in all required evaluations and procedures in this study protocol * Female subjects of childbearing potential must not be pregnant upon study entry * Male and female subjects who agree to use highly effective methods of birth control
Exclusion criteria
* known allergy to any of medications * chemotherapy taken within 21 days of study treatment * targeted therapy within 10 days of study treatment * BCR inhibitors within 24 hours of study treatment * major surgery within 4 weeks of first dose of study treatment * women who are pregnant * known infection with HIV or Hepatitis C * Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 6 months | ORR in subjects treated with combination of ibrutinib and obinutuzumab (with or without CHOP) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improved Hemoglobin and Platelet Counts. | 6 months | hematologic improvement |
| Progression Free Survival (PFS) | 6 months | time to progression post treatment of condition |
| To Evaluate Patient-reported Outcome (PRO) of Health-related Quality of Life by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACiT-Fatigue) | 1 year | health-related quality of life using FACIT Fatigue Scale |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fit Arm ibrutinib and obinutuzumab in combination with the CHOP regimen
Obinutuzumab: 100 mg on day 1 and 900 mg on day 2 Cycle 1, 1000 mg on day 8 and 15 of Cycle 1, and 1000 mg on day 1 of Cycles 2-6
Ibrutinib: 560mg po daily
CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone | 3 |
| Frail Arm ibrutinib and obinutuzumab
Obinutuzumab: 100 mg on day 1 and 900 mg on day 2 Cycle 1, 1000 mg on day 8 and 15 of Cycle 1, and 1000 mg on day 1 of Cycles 2-6
Ibrutinib: 560mg po daily | 0 |
| Total | 3 |
Baseline characteristics
| Characteristic | Fit Arm | Frail Arm | Total |
|---|---|---|---|
| Age, Customized >= 18 Years | 3 Participants | 0 Participants | 3 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 0 |
| other Total, other adverse events | 3 / 3 | 0 / 0 |
| serious Total, serious adverse events | 2 / 3 | 0 / 0 |
Outcome results
Primary
Overall Response Rate (ORR)
ORR in subjects treated with combination of ibrutinib and obinutuzumab (with or without CHOP)
Time frame: 6 months
Population: No data was collected for this outcome measure.
Secondary
Number of Participants With Improved Hemoglobin and Platelet Counts.
hematologic improvement
Time frame: 6 months
Population: No data was collected for this outcome measure.
Secondary
Progression Free Survival (PFS)
time to progression post treatment of condition
Time frame: 6 months
Population: No participants were enrolled into the Frail Arm. No data was collected for the Frail Arm, there are no results to report. Data reported for the Fit Arm is estimated.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Fit Arm | Progression Free Survival (PFS) | 23.5 Months | Standard Deviation 1.9 |
Secondary
To Evaluate Patient-reported Outcome (PRO) of Health-related Quality of Life by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACiT-Fatigue)
health-related quality of life using FACIT Fatigue Scale
Time frame: 1 year
Population: No data was collected for this outcome measure.