Chronic Lymphocytic Leukemia
Conditions
Keywords
Lymphocytic, Leukemia, CLL, Blood disease, White blood cells, Bone marrow disease, Immunotherapy
Brief summary
The purpose of this study is to evaluate the impact of sequential overlapping treatment with PD-1 monoclonal antibody (mAb), pembrolizumab/MK-1375, followed by ibrutinib on endogenous immune function in previously untreated, high-risk CLL patients. Immune function will be evaluated through various laboratory correlative tests.
Interventions
DRUGPembrolizumab
Pembrolizumab will be administered intravenously (IV) at 200 mg every 3 weeks for 1 year and up to 2 years.
DRUGIbrutinib
Ibrutinib will be administered orally once daily at approximately the same time each day at the dose of 420 mg daily (3 capsules of 140 mg daily).
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Merck Sharp & Dohme LLC
Janssen Scientific Affairs, LLC
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
* Have high risk CLL * Have documented previously untreated CLL according to IWCLL criteria * Willing and able to provide written informed consent * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Demonstrate adequate organ function * Able to take oral medication and willing to adhere to the medication regimen
Exclusion criteria
* Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment * Meets IWCLL criteria to start therapy * Has had any treatment for CLL including any investigational agent, chemotherapy, mAb, anti-PD-1, anti-PDL-1, or anti-CTLA-4 * Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leukemia) * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment * Major surgery or a wound that has not fully healed within 4 weeks of first dose * Additional criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) to the Therapeutic Intervention | Up to 2 years | Response categories according to The International Workshop on Chronic Lymphocytic Leukemia (IWCLL): Complete remission (CR); Complete remission with incomplete marrow recovery (CRi); Partial remission (PR); Progressive disease (PD); Stable disease (SD), defined as not meeting criteria for CR, CRi, PR or PD. |
| Time to Best Response | Up to 2 years | Time to best response to chronic lymphocytic leukemia (CLL) to the therapeutic intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to 2 years | Progressive disease (PD), defined as ≥ 50% rise in lymphocyte count to \> 5 x10\^9/L, ≥ 50% increase in lymphadenopathy, ≥ 50% increase in liver or spleen size, Richter's transformation, or new cytopenias due to CLL. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJulio Chavez, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab and Ibrutinib Treatment with pembrolizumab and ibrutinib and follow-up period of up to 24 months.
Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK). Ibrutinib is a small-molecule inhibitor of BTK.
Pembrolizumab: Pembrolizumab will be administered intravenously (IV) at 200 mg every 3 weeks for 1 year and up to 2 years.
Ibrutinib: Ibrutinib will be administered orally once daily at approximately the same time each day at the dose of 420 mg daily (3 capsules of 140 mg daily). | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Pembrolizumab and Ibrutinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 3 / 5 |
Outcome results
Primary
Overall Response Rate (ORR) to the Therapeutic Intervention
Response categories according to The International Workshop on Chronic Lymphocytic Leukemia (IWCLL): Complete remission (CR); Complete remission with incomplete marrow recovery (CRi); Partial remission (PR); Progressive disease (PD); Stable disease (SD), defined as not meeting criteria for CR, CRi, PR or PD.
Time frame: Up to 2 years
Population: evaluable participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pembrolizumab and Ibrutinib | Overall Response Rate (ORR) to the Therapeutic Intervention | CR/PR | 2 participants |
| Pembrolizumab and Ibrutinib | Overall Response Rate (ORR) to the Therapeutic Intervention | Stable Disease | 1 participants |
Primary
Time to Best Response
Time to best response to chronic lymphocytic leukemia (CLL) to the therapeutic intervention.
Time frame: Up to 2 years
Population: evaluable participants
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Pembrolizumab and Ibrutinib | Time to Best Response | 3.02 months | Standard Deviation 4.99 |
Secondary
Progression-free Survival (PFS)
Progressive disease (PD), defined as ≥ 50% rise in lymphocyte count to \> 5 x10\^9/L, ≥ 50% increase in lymphadenopathy, ≥ 50% increase in liver or spleen size, Richter's transformation, or new cytopenias due to CLL.
Time frame: Up to 2 years
Population: Evaluable patients
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Pembrolizumab and Ibrutinib | Progression-free Survival (PFS) | 16.57 months | Standard Deviation 1.58 |