A Phase 1/2 interventional study of Ibrutinib and Carfilzomib in Multiple Myeloma, sponsored by Pharmacyclics LLC.. Completed at 17 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-12-21.
Sponsored by Pharmacyclics LLC. · Phase 1/2, Interventional, and Treatment
A MULTICENTER PHASE 1/2B STUDY OF THE BRUTON'S TYROSINE KINASE INHIBITOR, IBRUTINIB (PCI-32765), IN COMBINATION WITH CARFILZOMIB (KYPROLIS™) IN SUBJECTS WITH RELAPSED OR RELAPSED AND REFRACTORY MULTIPLE MYELOMA
Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoietic cells other than T cells and is necessary for downstream signal transduction from various hematopoietic receptors including the B cell receptor as well as some Fc, chemokine, and adhesion receptors, and is crucial for both B cell development and osteoclastogenesis. Although down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from many myeloma patients and some cell lines. PCI-32765 is a potent and specific inhibitor of Btk currently in Phase 2 and 3 clinical trials. The current study is designed and intended to determine the safety and efficacy of PCI-32765 in combination with carfilzomib (Kyprolis™) with and without dexamethasone in subjects with relapsed or relapsed and refractory multiple myeloma (MM).
3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.
This study's enrollment of 84 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.
Browse Multiple Myeloma studies →Pharmacyclics LLC. is the lead sponsor of 54 studies on the registry; none are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 9 (90%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Measurable disease of MM as defined by at least ONE of the following:
Inclusion Criteria for Phase 2 Sub-study Cohort:
Subject must have received a regimen containing carfilzomib in combination with dexamethasone as their most recent line of therapy and have:
Achieved less than a partial response (\<PR) following at least 4 cycles and are without evidence of progression disease (PD).
OR
Exclusion Criteria:
Exclusion Criteria for Phase 2 Sub-study Cohort:
Ibrutinib PO 560mg + Carfilzomib IV 20/27mg/m2 + Dexamethasone PO 20mg
Drug: Ibrutinib · Drug: Carfilzomib · Drug: Dexamethasone
Ibrutinib PO 560mg + Carfilzomib IV 20/36mg/m2 + Dexamethasone PO 20mg
Drug: Ibrutinib · Drug: Carfilzomib · Drug: Dexamethasone
Ibrutinib PO 840 mg + Carfilzomib IV 20/36 mg/m2 + Dexamethasone PO 20 mg
Drug: Ibrutinib · Drug: Carfilzomib · Drug: Dexamethasone
Overall Response Rate (ORR)
-To evaluate the overall response (ORR) of ibrutinib in combination with carfilzomib and dexamethasone.
Time frame: up to 4 years
Duration of Response (DOR)
The time interval between the date of initial documentation of a response (PR or better) and the date of first documented evidence of progressive disease, death, or date of censoring for the subjects who had not progressed/died. The censoring date was the last adequate tumor assessment date.
Time frame: Up to 4 years
Overall Survival
Time from date of first dose of study treatment to the date of death from any cause
Time frame: Up to 4 years
Progression Free Survival (PFS)
Time from date of first dose of study treatment to the date of first documented evidence of progressive disease, death or date of censoring for the subjects not progressed/died. The censoring date was the last adequate tumor assessment date.
Time frame: Up to 4 years
| Milestone | Cohort 1 (560 mg) | Cohort 2a (560 mg) | Cohort 2b (560 mg) | All RP2D (840 mg) |
|---|---|---|---|---|
| Started | 3 | 5 | 17 | 59 |
| Completed | 3 | 5 | 17 | 59 |
| Not completed | 0 | 0 | 0 | 0 |
-To evaluate the overall response (ORR) of ibrutinib in combination with carfilzomib and dexamethasone.
| Participants | Cohort 1 (560 mg) | Cohort 2a (560 mg) | Cohort 2b (560 mg) | All RP2D (840 mg) |
|---|---|---|---|---|
| Overall Response Rate (ORR) | 2 | 2 | 12 | 42 |
The time interval between the date of initial documentation of a response (PR or better) and the date of first documented evidence of progressive disease, death, or date of censoring for the subjects who had not progressed/died. The censoring date was the last adequate tumor assessment date.
| Months | Cohort 1 (560 mg) | Cohort 2a (560 mg) | Cohort 2b (560 mg) | All RP2D (840 mg) |
|---|---|---|---|---|
| Duration of Response (DOR) | 7.1 (1.2 to 13.0) | 15.3 (5.4 to 15.3) | 9.2 (3.0 to 14.5) | 7.2 (2.7 to 16.6) |
Time from date of first dose of study treatment to the date of death from any cause
| Months | All RP2D (840 mg) |
|---|---|
| Overall Survival | 35.9 (0.9 to 51.8) |
Time from date of first dose of study treatment to the date of first documented evidence of progressive disease, death or date of censoring for the subjects not progressed/died. The censoring date was the last adequate tumor assessment date.
| Months | All RP2D (840 mg) |
|---|---|
| Progression Free Survival (PFS) | 7.4 (4.6 to 10.2) |
Collected over 4 years, 2months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1 (560 mg) | 0/3 (0%) | 2/3 (66.7%) | 3/3 (100%) |
| Cohort 2a (560 mg) | 4/5 (80%) | 5/5 (100%) | 5/5 (100%) |
| Cohort 2b (560 mg) | 9/17 (52.9%) | 17/17 (100%) | 17/17 (100%) |
| All RP2D (840 mg) | 22/59 (37.3%) | 59/59 (100%) | 58/59 (98.3%) |
| Event | Cohort 1 (560 mg) | Cohort 2a (560 mg) | Cohort 2b (560 mg) | All RP2D (840 mg) |
|---|---|---|---|---|
| PneumoniaInfections and infestations | 1/3 | 2/5 | 1/17 | 6/59 |
| Atrial FlutterCardiac disorders | 1/3 | 0/5 | 0/17 | 1/59 |
| ConstipationGastrointestinal disorders | 0/3 | 1/5 | 0/17 | 0/59 |
| DiarrhoeaGastrointestinal disorders | 0/3 | 1/5 | 2/17 | 0/59 |
| AstheniaGeneral disorders | 0/3 | 1/5 | 0/17 | 0/59 |
| Clostridium difficile colitisInfections and infestations | 0/3 | 1/5 | 0/17 | 1/59 |
| Gastrointestinal infectionInfections and infestations | 0/3 | 1/5 | 0/17 | 1/59 |
| Plasma cell myelomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/3 | 1/5 | 0/17 | 1/59 |
| Metastases to central nervous systemNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/3 | 1/5 | 0/17 | 0/59 |
| Non - small cell lung cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/3 | 1/5 | 0/17 | 0/59 |
| Event | Cohort 1 (560 mg) | Cohort 2a (560 mg) | Cohort 2b (560 mg) | All RP2D (840 mg) |
|---|---|---|---|---|
| FatigueGeneral disorders | 0/3 | 4/5 | 12/17 | 27/59 |
| DiarrhoeaGastrointestinal disorders | 0/3 | 3/5 | 11/17 | 29/59 |
| AnaemiaBlood and lymphatic system disorders | 1/3 | 3/5 | 6/17 | 24/59 |
| PyrexiaGeneral disorders | 1/3 | 3/5 | 8/17 | 12/59 |
| ChillsGeneral disorders | 0/3 | 3/5 | 1/17 | 7/59 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/3 | 3/5 | 0/17 | 10/59 |
| Peripheral sensory neuropathyNervous system disorders | 0/3 | 3/5 | 3/17 | 13/59 |
| EpistaxisRespiratory, thoracic and mediastinal disorders | 0/3 | 3/5 | 5/17 | 10/59 |
| ThrombocytopeniaBlood and lymphatic system disorders | 1/3 | 1/5 | 3/17 | 30/59 |
| HeadacheNervous system disorders | 1/3 | 2/5 | 8/17 | 13/59 |
| Age, Categorical(Participants) | Cohort 1 (560 mg) | Cohort 2a (560 mg) | Cohort 2b (560 mg) | All RP2D (840 mg) | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 0 | 1 | 12 | 33 | 46 |
| >=65 years | 3 | 4 | 5 | 26 | 38 |
| Age, Continuous(years) | Cohort 1 (560 mg) | Cohort 2a (560 mg) | Cohort 2b (560 mg) | All RP2D (840 mg) | Total |
|---|---|---|---|---|---|
| Median | 69.0 ± 1.53 | 72.0 ± 9.21 | 60.0 ± 10.29 | 63.0 ± 9.86 | 63.5 ± 9.88 |
| Sex: Female, Male(Participants) | Cohort 1 (560 mg) | Cohort 2a (560 mg) | Cohort 2b (560 mg) | All RP2D (840 mg) | Total |
|---|---|---|---|---|---|
| Female | 1 | 1 | 11 | 28 | 41 |
| Male | 2 | 4 | 6 | 31 | 43 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1 (560 mg) | Cohort 2a (560 mg) | Cohort 2b (560 mg) | All RP2D (840 mg) | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 2 | 7 | 10 |
| Not Hispanic or Latino | 2 | 5 | 15 | 51 | 73 |
| Unknown or Not Reported | 0 | 0 | 0 | 1 | 1 |
| Region of Enrollment(participants) | Cohort 1 (560 mg) | Cohort 2a (560 mg) | Cohort 2b (560 mg) | All RP2D (840 mg) | Total |
|---|---|---|---|---|---|
| United States | 3 | 5 | 17 | 59 | 84 |
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Pharmacyclics LLC.