A Phase 1 Pharmacokinetic-Pharmacodynamic Study of Avelumab (MSB00100718C) in Patients with Previously Treated Advanced Stage Classical Hodgkin*s Lymphoma

Withdrawn

Conditions: Hodgkin's Lymphoma
lymph node cancer
10025319

Registration Number: NL-OMON43446

Lead Sponsor: Pfizer

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

1. Histological confirmation of classical Hodgkin's Lymphoma (cHL) with relapsed or refractory disease, who either have had prior autologous or allogenic stem cell transplantation (SCT) or are not eligible for SCT.
2. Patients must be off previous cHL therapy for at least 28 days prior to
randomization.
3. At least 1 FDG-PET-avid (Deauville 4/5) measurable lesion >1.5 cm as defined by Response Criteria for Malignant Lymphoma that has not previously been irradiated.
4. Age *18 years.
5. Estimated life expectancy of at least 3 months.
6. ECOG Performance Status (PS) 0 or 1.
7. Adequate bone marrow function including:
a. Absolute neutrophil count (ANC) *1,000/mm3 or *1.0 x 109/L (may have received G-CSF support);
b. Platelets *50,000/mm3 or *50 x 109/L;
c. Hemoglobin *8.0 g/dL (>4.9 mmol/L) (may have been transfused).
8. A pre-treatment tumor biopsy (lymph node or bone marrow) is mandatory at baseline for the expansion phase. A pre-treatment tumor biopsy in the lead in phase and an on-treatment biopsy in both phases are optional. Baseline biopsy must be collected within 28 days prior to
randomization.
9. Adequate Renal Function: Estimated creatinine clearance *30 mL/min as calculated using the Cockcroft-Gault (CG) equation.
10. Adequate Liver Function, including:
a. Total serum bilirubin *1.5 x upper limit of normal (ULN);
b. Aspartate and Alanine transaminase (AST and ALT) *2.5 x ULN.
11. International Normalized Ratio (INR) or prothrombin time (PT) <1.5 x ULN.
12. Serum or urine pregnancy test (for females of childbearing potential)
negative at screening.
13. Male patients able to father children and female patients of childbearing potential and at risk for pregnancy must agree to use 2 highly effective method(s) of contraception throughout the study and for at least 60 days after the last dose of assigned treatment. Female patients who are not of childbearing potential (ie, meet at least one of the following criteria):
* Have undergone a documented hysterectomy and/or bilateral oophorectomy;
* Have medically confirmed ovarian failure; or
* Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; a serum follicle-stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal
women.
14. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study. As inclusion of adult patients for whom consent must be provided by a legally authorized representative is not appropriate for this research, this protocol excludes adult individuals who lack capacity to consent for themselves.
15. Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.

Exclusion Criteria

1. Patients with prior allogeneic stem cell transplantation (SCT) who
have had:
a. allo-SCT performed <12 months prior to randomization; or
b. immunosuppressive treatment for acute or chronic graft-versus-host disease (GVHD) within 3 months prior to randomization (with the exception of those patients who required * 15 mg/day oral prednisone or equivalent); or
c. acute Grade 3 or Grade 4 GVHD at any time in the past (as defined by the modified Seattle Glucksberg Criteria29); or
d. prior chronic GVHD (as defined by the NIH Consensus Development Project30), persisting for >6 months, which required systemic immunosuppression (with the exception of those patients who required * 15 mg/day oral prednisone or equivalent); or
e. a donor lymphocyte infusion (DLI) within 6 months prior to randomization.
2. Prior therapy with an anti-PD-1 or anti-PD-L1. May be enrolled if patient had stopped prior anti-PD1 therapy more than one year ago and had responded.
3. Persisting toxicity related to prior therapy NCI CTCAE v4.0 Grade >1, except alopecia; also, sensory neuropathy Grade * 2 is acceptable.
4. Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry.
5. Prior palliative radiotherapy to lesion(s) is permitted as long as there is at least one target lesion evaluable for anti-tumor activity.
6. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy, or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
7. Current or prior use of immunosuppressive medication within 7 days prior to randomization, except the following: Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection); Systemic corticosteroids at physiologic doses * 10 mg/day of
prednisone or equivalent; Steroids as premedication for hypersensitivity
reactions (eg, CT scan premedication).
8. Active autoimmune disease that might deteriorate when receiving an
immunostimulatory agents. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
9. Known severe hypersensitivity reactions to monoclonal antibodies
(Grade * 3 NCI-CTCAE v 4.03).
10. Active infection requiring systemic therapy.
11. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
12. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
13. Diagnosis of any other malignancy within 5 years prior to registration, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or lowgrade (Gleason 6 or below) prostate cancer on surveillance without any
plans for treatment intervention (eg, surgery, radiation, or castration).
14. Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation.
15. Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Endpoints<br /><br>* Percent TO by dose/schedule in peripheral blood immune cells, including CD14+<br /><br>monocytes and CD3+ T cells.<br /><br>* Pharmacokinetic parameters of avelumab including, but not limited to, Cmax,<br /><br>Tmax, AUClast, Tlast, AUC sd,, t1/2, AUCsd,inf, CL, and Vz as data permit.<br /><br>Multiple Dose (MD) Css,max, Tss,max, AUCss,, t1/2, Css,min, Css,av, CL, and<br /><br>Vss, ,Rac (AUCss,* /AUCsd,) and Rss (AUCss, /AUCsd,inf) as data permit.</p><br>

Secondary Outcome Measures