Classical Hodgkin Lymphoma, Recurrent Hodgkin Lymphoma, Refractory Hodgkin Lymphoma
Conditions
Brief summary
This phase II trial evaluates how effective 560 mg of ibrutinib taken by mouth daily is in the treatment of classical Hodgkin lymphoma which recurs or does not respond to initial treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth, by altering the environment around the tumor or by affecting the immune system.
Detailed description
PRIMARY OBJECTIVES: I. To determine the antitumor efficacy of single agent ibrutinib as measured by the overall response rate in patients with relapsed/refractory Hodgkin's lymphoma who have relapsed or not responded to chemotherapy, immunotherapy and/or radiation. SECONDARY OBJECTIVES: I. To assess duration of tumor control including duration of response (DOR) II. To assess progression free survival (PFS). III. To assess the safety and tolerability of 560mg of ibrutinib in Hodgkin lymphoma (HL) patients. TERTIARY OBJECTIVES: I. To assess the mechanism(s) by which ibrutinib may be active in patients with classical Hodgkin lymphoma (cHL) by the correlation of potential biomarkers with clinical outcomes. OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days then every 9 weeks for 1 year.
Interventions
DRUGIbrutinib
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPharmacological Study
Correlative studies
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos 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
* Patients with relapsed or refractory classical HL who have previously received autologous stem cell transplant and/or allogeneic stem cell transplant. Patients must have received prior autologous stem cell transplant at least 12 weeks (3 months) before the first dose of ibrutinib and/or allogeneic stem cell transplant must have been completed at least 6 months prior to the first dose of Ibrutinib. OR * Patients with relapsed or refractory HL who have failed at least 2 lines of prior therapy and are not eligible for autologous stem cell transplant due to: * Inability to achieve a CR or PR prior to transplant * Age or comorbid conditions * Inability to collect stem cells * Completion of any prior treatment with radiation, chemotherapy, biologics, and/or other investigational agents at least 4 weeks prior to the first dose of ibrutinib. Patients must have completed any prior immunotherapy (e.g., rituximab or PD-1 inhibition) or antibody drug conjugate therapy (e.g. brentuximab vedotin) at least 4 weeks prior to the first dose of ibrutinib in the absence of clear disease progression. * Prior treatment with at least 2 lines of therapy for HL including brentuximab vedotin. In those patients who cannot receive brentuximab vedotin, treatment with 2 prior therapeutic regimens is sufficient. * Fluorodeoxyglucose (FDG)-avid disease by PET and measurable disease of at least 1.5 cm in minimum dimension by CT scan with contrast, as assessed by the site radiologist. * Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening and randomization, with the exception of PEGylated GCSF (pegfilgrastim) and darbopoeitin which require at least 14 days prior to screening and randomization defined as: * Absolute neutrophil count \>750 cells/mm3 (0.75 x 109/L). * Platelet count \>50,000 cells/mm3 (50 x 109/L). * Hemoglobin \>8.0 g/dL. * Adequate hepatic and renal function defined as: * Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN). * Estimated Creatinine Clearance ≥30 ml/min (Cockcroft-Gault) * Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin) * PT/INR \<1.5 x ULN and PTT (aPTT) \<1.5 x ULN. * Men and women ≥ 18 years of age. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. * Female subjects who are of non-reproductive potential (i.e., post-menopausal by history-no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry. * Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], sexual abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study drug * Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
Exclusion criteria
* Prior allogeneic Stem cell transplant within 6 months. * Active GVHD or concurrent treatment with immunosuppressive medications as prophylaxis for GVHD * Previous therapy with BTK inhibition * Known cerebral/meningeal disease * Nodular lymphocyte predominant Hodgkin's Lymphoma subtype * Concurrent therapy with other systemic anti-neoplastic or investigational agents * Patients with a known hypersensitivity to any excipient contained in the drug formulation * History of other malignancies, except: * Malignancy treated with curative intent and with no known active disease present for ≥3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician. * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. * Adequately treated carcinoma in situ without evidence of disease. * Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration \[\>14 days\] of \>20 mg/day of prednisone) within 28 days of the first dose of study drug. * Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug * Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug. * Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade ≤1, or to the levels dictated in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From date of study entry to date of progression or death up to 24 months | Overall response rate (ORR) defined as the proportion of participants having a complete (CR) and partial (PR) response. A one-sample binomial test will be used to assess ORR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | From date of documented tumor response, CR or PR, to date of disease progression or death, up to 24 months | Kaplan-Meier estimate of median DOR will be reported with 95% confidence intervals. |
| Progression Free Survival (PFS) | From date of study entry to date of progression or death up to 24 months. | Kaplan-Meier estimate of median PFS will be reported with 95% confidence intervals. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Ibrutinib) Patients receive ibrutinib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Didn't receive treatment | 2 |
| Overall Study | Inadequate response to therapy | 2 |
| Overall Study | Non-compliant | 5 |
| Overall Study | Patient decision to discontinue treatment | 3 |
| Overall Study | Possible progression per treating physician | 1 |
| Overall Study | Progression of disease | 15 |
Baseline characteristics
| Characteristic | Treatment (Ibrutinib) |
|---|---|
| Age, Continuous | 37.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 3 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants |
| Race/Ethnicity, Customized Race Unknown or Not reported | 4 Participants |
| Race/Ethnicity, Customized Race White | 20 Participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 16 Participants |
| Stage at Enrollment II | 4 Participants |
| Stage at Enrollment III | 11 Participants |
| Stage at Enrollment IV | 8 Participants |
| Stage at Enrollment Unknown | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 26 |
| other Total, other adverse events | 25 / 26 |
| serious Total, serious adverse events | 5 / 26 |
Outcome results
Primary
Overall Response Rate (ORR)
Overall response rate (ORR) defined as the proportion of participants having a complete (CR) and partial (PR) response. A one-sample binomial test will be used to assess ORR.
Time frame: From date of study entry to date of progression or death up to 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Ibrutinib) | Overall Response Rate (ORR) | 0.05 Proportion of participants |
Secondary
Duration of Response (DOR)
Kaplan-Meier estimate of median DOR will be reported with 95% confidence intervals.
Time frame: From date of documented tumor response, CR or PR, to date of disease progression or death, up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Ibrutinib) | Duration of Response (DOR) | 5.6 months |
Secondary
Progression Free Survival (PFS)
Kaplan-Meier estimate of median PFS will be reported with 95% confidence intervals.
Time frame: From date of study entry to date of progression or death up to 24 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Ibrutinib) | Progression Free Survival (PFS) | 4.6 months |