MDACC Study Summary 2008-0124

Study Summary
No. 2008-0124:.......Lymphoma......Nathan Fowler......Lymphoma/Myeloma

Study Summary Title



Study Summary Number:	2008-0124

Study Title:	A Phase 2 Study of VELCADEŽ (bortezomib) in Combination with Bendamustine and Rituximab in Subjects with Relapsed or Refractory, Follicular Lymphoma

Physician

New Patient Referral



Name:	Nathan Fowler	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:	Millennium Pharmaceuticals, Inc. in partnership with Johnson &Johnson Pharmaceutical Research and Development

Phase of Study:	Phase I/Phase II	Return Visit:	Screening Day,Cycle 1, Days, 1, 2, 8, 15, and 22. Cycles 2, 3, 4, and 5, Days 1, 2, 8, 15, and 22. End of Treatment, Follow-up visit, and End of Study visit.

Treatment Agents:	Bendamustine HCl Rituximab Velcade	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:

The goal of Part 1 of this clinical research study is to learn the highest
tolerable of 3 doses of bendamustine that can be given in combination with
Velcade™ (bortezomib) and rituximab to patients with follicular lymphoma.

The goal of Part 2 of this study is to learn if the combination of bortezomib,
bendamustine, and rituximab can help to control follicular lymphoma.

In both Parts 1 and 2, the safety of this drug combination will also be
studied.

Study Objectives / Outcomes

Primary Objective
The primary objective is to determine whether VELCADEŽ (bortezomib) in combination with bendamustine and rituximab provides benefit to subjects with relapsed or refractory follicular lymphoma as assessed by complete response (CR) rate (per revised International Working Group [IWG] criteria).

Secondary Objectives
ˇ To determine the maximum tolerated dose (MTD) of bendamustine in combination with VELCADEŽ and rituximab, up to a maximum bendamustine dose of 90 mg/m²ˇ
To evaluate the safety and tolerability of VELCADEŽ in combination with bendamustine and rituximab
To determine the overall response rate: complete response + partial response (ORR: CR + PR)
ˇ To determine Progression Free Survival (PFS)
ˇ To determine duration of response (DOR)

Exploratory Objectives
ˇ To determine if the extent of prior rituximab exposure or response to the last prior chemotherapy regimen correlates with efficacy of VELCADEŽ, bendamustine, and rituximab in this study ˇ Evaluate patient populations that generally exhibit poor outcomes after treatment with anti-lymphoma therapies through the analysis of a defined set of biomarkers including:
o Germline DNA variants linked to either lymphoma prognosis or efficacy of
specific anti-lymphoma therapy, eg, FCGR3A/FCGR2A, variants that are
linked to reduced rituximab efficacy

o Evaluation of protein prognostic markers of disease or drug activity.

Study Status Information



Study Activation / Registration Date:	08/13/2008

IRB Review and Approval Date:	06/10/2008

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	Approximately 75 participants

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) Male or female subject 18 years of age or older.

2) Pathological diagnosis of follicular lymphoma (any grade).

3) Documented relapse or progression following prior antineoplastic therapy.

4) Have received 4 or more prior doses of rituximab.

5) At least 1 measurable tumor mass (>1.5 cm in the long axis and >1.0 cm in the short axis that has not been previously irradiated, or has grown since previous irradiation).

6) No clinically significant central nervous system lymphoma.

7) Karnofsky performance status (KPS) >/=50 (equivalent to Eastern Cooperative Group Oncology Group [ECOG] status </=2.

8) The following clinical laboratory values within 21 days prior to enrollment: a) Absolute neutrophil count (ANC) >/=1.5 × 10^9 cells/L b) Platelets >/=100 × 10^9 cells/L c) Alanine transaminase (ALT) </=3× the upper limit of normal (ULN) d) Aspartate transaminase (AST) </=3× ULN e) Total bilirubin </=2× ULN f) Calculated creatinine clearance >/=40 mL/min.

9) Female subjects must be postmenopausal (for at least 6 months) or surgically sterile, or if sexually active, be practicing an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before study entry and throughout the study. They must have a negative serum beta-human chorionic gonadotropin (Beta-hCG) pregnancy test at screening.

10) Male subjects must agree to use an acceptable method of contraception for the duration of the study.

11) Subjects (or their legally acceptable representative) must have signed 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:

1) Diagnosed or treated for a malignancy other than NHL within 2 years of first dose, or who were previously diagnosed with a malignancy other than NHL and have any radiographic or biochemical marker evidence of malignancy. Subjects with prostate cancer who were treated with definitive radiotherapy and have a serum prostate-specific antigen (PSA) <1 ng/mL are not excluded. Subjects are also not excluded if they had basal cell or squamous cell carcinoma of the skin that was completely resected, or any in situ malignancy that was adequately treated.

2) Prior treatment with VELCADEŽ or bendamustine.

3) Antineoplastic (including unconjugated therapeutic antibodies and toxin immunoconjugates), experimental, or radiation therapy within 3 weeks before Day 1 of Cycle 1.

4) Nitrosoureas within 6 weeks before Day 1 of Cycle 1.

5) Radioimmunoconjugates within 10 weeks before Day 1 of Cycle 1.

6) Autologous stem cell transplant within 3 months before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time.

7) Major surgery within 2 weeks before Day 1 of Cycle 1.

8) Platelet transfusion within 7 days of Day 1 of Cycle 1 (applies to subjects enrolled in the dose escalation phase only. This does not apply to subjects enrolled in phase 2 of the study).

9) Ongoing therapy with corticosteroids. Prednisone </= 15 mg per day or its equivalent is allowed.

10) Residual toxic effects of >/=Grade 2 from previous therapy or surgery.

11) Peripheral neuropathy of >/=Grade 2 due to any cause.

12) History of allergic reaction/hypersensitivity attributable to compounds containing boron, mannitol, polysorbate 80 or sodium citrate dehydrate, or anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab.

13) Concurrent treatment with another investigational agent.

14) Female subject who is pregnant or breast-feeding.

15) Known history of human immunodeficiency virus (HIV) infection

16) Active systemic infection requiring therapy

17) Serious medical or psychiatric illness likely to interfere with participation in this clinical study

18) Myocardial infarction within 6 months prior to enrollment or New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities in the opinion of the investigator

Links

Registration Number: NCT00636792
Study Information on Clinical Trials Registry (clinicaltrials.gov)