MDACC Study Summary 2008-0062

Study Summary
No. 2008-0062:.......Lymphoma......Michelle A. Fanale......Lymphoma/Myeloma

Study Summary Title



Study Summary Number:	2008-0062

Study Title:	A phase IA/II, multi-center, open-label study of HCD122 administered intravenously once weekly for four weeks in adult patients with advanced non-Hodgkin's or Hodgkin's lymphoma who have progressed after at least two prior therapies

Physician

New Patient Referral



Name:	Michelle A. Fanale	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Lymphoma/Myeloma	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2860 Contact us about clinical trials

General Information



Disease Group:	Lymphoma	Supported By:	Novartis

Phase of Study:	Phase I/Phase II	Return Visit:	Screening Day (within 28 days of infusion). Days 1, 2, 3, 5, 8, 15, 22, 23, 24, 26, 29, 36, 43, 50, 106. Follow-up visit on Day 162 and End of Study visit.

Treatment Agents:	HCD122	Home Care:	N/A

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	N/A


Description/ Intervention:	Unavailable

Study Objectives / Outcomes

Dose escalation phase
Primary objectives
1. To determine the maximum tolerated dose (MTD) or the recommended Phase II dose of HCD122 when administered as a single agent intravenously (IV) once weekly for 4 weeks to adult patients with advanced non-Hodgkin's or Hodgkin's lymphoma who have progressed after at least two prior therapies

Secondary objectives
1. To characterize safety and tolerability of single agent HCD122, including acute and chronic toxicities
2. To characterize the pharmacokinetic (PK) profile after single and repeated doses of single agent HCD122 on a once weekly dosing schedule for 4 weeks
3. To assess the immunogenicity of HCD122
4. To characterize the CD40 occupancy profile of HCD122 on peripheral CD19(+) B cells after single and repeated doses
5. To quantify pre- and post-treatment changes in [¹⁸F]-FDG uptake as a pharmocodynamic read-out in selected patients at the selected study sites
6. To assess preliminary anti-tumor activity (including tumor response, duration of response, time to progression, and progression free survival) in dose escalation patients with advanced non-Hodgkin's or Hodgkin's lymphoma who have progressed after at least two prior therapies

Exploratory objectives
1. To characterize CD40 occupancy profile of HCD122 on lymphoma cells, pre- and posttreatment
2. To characterize pharmacodynamic response to HCD122 by assessing pre- and posttreatment peripheral blood CD19(+) B cells
3. To characterize additional candidate pharmacodynamic markers in blood (e.g. sCD40L, sCD40, total immunoglobulins, cytokines [retrospective analysis if clinical response is observed], and other leukocyte subsets), pre- and post-treatment
4. To investigate candidate predictive markers (e.g. sCD40 and FcgIIIR polymorphism) in blood

Dose expansion phase
Primary objectives
1. To assess clinical response at the MTD or the recommended phase II dose in adult patients with advanced non-Hodgkin's or Hodgkin's lymphoma who have received at least two prior therapies

Secondary objectives
1. To characterize safety and tolerability of single agent HCD122, including acute and chronic toxicities
2. To characterize the pharmacokinetic (PK) profile after single and repeated doses of single agent HCD122 on a once weekly dosing schedule for 4 weeks for the first 40 patients in dose expansion phase
3. To assess the immunogenicity of HCD122
4. To characterize the CD40 occupancy profile of HCD122 on peripheral CD19(+) B cells after single and repeated doses
5. To quantify pre- and post-treatment changes in [¹⁸F]-FDG uptake as a pharmocodynamic read-out in in selected patients at the selected study sites
6. To assess the duration of response, time to progression, and progression free survival in dose expansion patients with advanced non-Hodgkin's or Hodgkin's lymphoma who have received at least two prior therapies

Exploratory objectives

Study Status Information



Study Activation / Registration Date:	11/10/2008

IRB Review and Approval Date:	04/24/2008

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	Up to 230 patients

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patients must have confirmed diagnosis, according to the Revised European American lymphoma/World Health Organization [REAL/WHO] classification, of the following Bcell lymphomas: 1. Follicular lymphoma (FL) 2. Marginal zone lymphoma (MZL)/mucosa-associated lymphoid tissue (MALT) 3. Diffuse large B-cell lymphoma (DLBCL) 4. Mantle cell lymphoma (MCL), OR 5. Hodgkin lymphoma (HL)

2) Patients must have progressed after at least 2 prior therapies (autologous stem cell transplantation is considered as 1 therapy): 1. Patient must receive at least one prior therapy with a rituximab containing regimen if it is indicated as the standard of care 2. If patient received autologous stem cell transplantation, patient must have received at least 1 prior systemic therapy 3. If patient did not receive autologous stem cell transplantation, patient must have received at least 2 prior systemic therapies

3) Patients who received autologous stem cell transplantation: 1. Must be at least 12 weeks post-transplant prior to study drug, AND 2. Must have recovered fully from the side effects of such treatment prior to beginning study treatment.

4) Patients who have NOT received autologous stem cell transplantation: 1. Must be ineligible for the autologous stem cell transplantation, OR 2. If eligible, patients chose not to receive stem cell transplant

5) Patients must have discontinued any previous anticancer and investigational therapy including radiation therapy for at least 21 days prior to study drug, and must have recovered fully from the side effects of such treatment prior to beginning study drug.

6) Patients must have discontinued previous monoclonal antibody (except rituximab) or radioimmunotherapy administration for at least 60 days prior to study drug, and are confirmed either have no response to that therapy or have disease progression after the treatment. Patients must have recovered fully from the side effects of that treatment prior to beginning study treatment.

7) For patients who received rituximab containing regimen, rituximab should be discontinued for at least 28 days prior to study drug, are confirmed to either have no response or have disease progression after rituximab treatment, and must have recovered fully from the side effects of such treatment prior to beginning study drug.

8) Patients must not have undergone major surgery within 30 days prior to study drug, and must have recovered fully from the side effects of any major or minor surgical procedures prior to study treatment.

9) Patients must be >/= 18 years

10) Patients must have WHO Performance Status grade 0, 1, or 2

11) Patients must meet the following laboratory criteria (must be obtained within 14 days of enrollment): 1. Absolute neutrophil count (ANC) >/= 1,000/uL 2. Platelet count >/= 75 x 10^3/uL (must not have been transfused within previous 10 days) 3. Hemoglobin >/= 8.0 g/dL (may have been transfused) 4. Serum creatinine </= 1.5 x ULN 5. AST </= 2.5 x ULN; ALT </= 2.5 x ULN 6. Serum bilirubin </= 1.5 x ULN 7. Serum amylase </= ULN 8. Serum lipase </= ULN 9. Fasting serum triglyceride level </= 500 mg/dL

12) Patients must have at least one site of measurable disease, in addition to any site(s) biopsied (either fine needle biopsy or core biopsy), defined as follows: 1. Clearly measurable (i.e., well-defined boundaries) in at least two perpendicular dimensions on imaging scan 2. Lymph node or nodal mass bi-dimensional measurement with > 1.5 cm in longest transverse diameter

13) Patients with Hodgkin's lymphoma or diffuse large B-cell lymphoma must have a positive [^18 F]-FDG-PET scan as defined in the Cheson response criteria at baseline

14) Patients must have life expectancy > 3 months

15) Patients must sign the informed consent form and be willing and able to comply with the study protocol.

Exclusion Criteria:

1) Patients who have been treated with any anti-CD40 antibody

2) Patients who have received prior allogeneic stem cell transplant

3) Patients who have had a prior anaphylactic or other severe infusion reaction such that the patient is unable to tolerate human immunoglobulin or monoclonal antibody administration

4) Patients who are taking systemic corticosteroids, except for a dose up to 100 mg of hydrocortisone or equivalent as premedication administered prior to certain medications or blood products

5) Patients who have current drug or alcohol abuse

6) Patients who have history or clinical evidence of central nervous system, meningeal, or epidural disease including brain metastasis

7) Impaired cardiac function or clinically significant cardiac disease, including any one of the following: 1. New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant arrhythmia, congestive heart failure, or cardiomyopathy 2. Angina pectoris </= 3 months prior to starting study drug 3. Acute MI </= 3 months prior to starting study drug 4. Other clinically significant heart disease (e.g., uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)

8) Patients who have history of pancreatic disease (e.g., acute or chronic pancreatitis, etc.) or any surgery of the pancreas

9) Patients who have gallbladder stone, cystic fibrosis, or any other risk factors that may increase the risk of pancreatitis

10) Patients who have history of active infection (viral, bacterial, or fungal) requiring systemic therapy within 4 weeks prior to enrollment. Prophylactic antibiotics and anti-viral therapies are permitted

11) Patients who have active autoimmune disease requiring immunosuppressive therapy

12) Known diagnosis of human immunodeficienty virus (HIV) infection

13) Patients with positive serology for hepatitis B (by HBsAg) or active hepatitis C infection

14) Patients who have history of another primary malignancy that is currently clinically significant or currently requires active intervention

15) Women of child-bearing potential (WCBP) who are pregnant or breast feeding. WCBP, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test </= 72 hours prior to starting study treatment. In addition, all sexually active WCBP and male patients must agree to use adequate contraceptive methods throughout the study.

Links

Registration Number: NCT00670592
Study Information on Clinical Trials Registry (clinicaltrials.gov)