A Phase I/II Trial of VR-CHOP in Lymphoma Patients

Follicular Lymphoma Clinical Trial

Official title:

A Phase I/II Trial of VR-CHOP for Patients With Untreated Follicular Lymphoma and Other Low Grade B-Cell Lymphomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00634179
• Other study ID #: IRB00002996
• Secondary ID: X05215
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 11, 2008
• Last updated: February 17, 2016
• Start date: February 2008
• Est. completion date: November 2015

Study information

• Verified date: February 2016
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardUnited States: Data and Safety Monitoring Board
• Study type: Interventional

Clinical Trial Summary

This is an open-label (doctors and patients know which drug will be given), single center, phase 1/2 clinical trial. The primary objective is to determine whether VR-CHOP provides benefit to patients with previously untreated indolent non-Hodgkin's lymphomas (NHL).

Description:

This study will assess whether adding bortezomib (Velcade) to R-CHOP (in a new combination called VR-CHOP) can further improve outcomes in patients with indolent NHL who have not previously received treatment.

Patients who are eligible to take part in the study will receive VR-CHOP at the doses of Velcade and vincristine established in phase 1. Patients will receive VR-CHOP for up to 8 cycles of treatment (each of 21 days duration). During treatment, patients will be assessed for their response to therapy and for possible side effects. All patients will go on to receive maintenance therapy after completion of their initial treatment as designed by the protocol.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Tissue diagnosis of a previously untreated, cluster of differentiation antigen 20+ (CD20+), B-cell non-Hodgkin lymphoma.

• For the Phase 1 trial: patients with any of the following diagnoses are eligible:

• Follicular Lymphomas (Grade 1, 2, 3a, 3b)

• Small Lymphocytic Lymphoma

• Marginal Zone Lymphomas

• For the Phase 2 trial: patients with any of the following diagnoses are eligible:

• Follicular Lymphomas (Grade 1, 2, 3a)

• Small Lymphocytic Lymphoma

• Marginal Zone Lymphomas

• Patients with follicular or other low-grade lymphoma must have an indication for treatment based on modified Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria or a Follicular Lymphoma International Prognostic Index (FLIPI) score = 3.

• Indications for treatment based on modified GELF criteria include any one of the following:

• B symptoms or other lymphoma-related symptoms

• Involvement of 3 nodal sites, each with a diameter of 3 cm

• Any nodal or extranodal tumor mass with a diameter of 7 cm

• Splenomegaly greater than 16 cm by CT scan.

• Pleural effusions or peritoneal ascites

• Cytopenias (leukocytes < 1.0 x 10 /L and/or platelets < 100 x 10/L)

• Leukemia (> 5.0 x 10 /L circulating malignant cells)

• Indications for treatment based on FLIPI criteria include any three of the following:

• Age = 60 years

• Ann Arbor stage III or IV

• Hemoglobin level < 120 g/L

• Number of nodal areas involved > 4

• Serum lactate dehydrogenase (LDH) level > normal

• Only chemotherapy-naïve subjects are eligible. Subjects may have received prednisone (< 2 months of therapy) or radiation = 2 sites of therapy.

• Voluntary written informed consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.

• Female patients of child bearing potential must have a negative ß-human chorionic gonadotropin (ß-hCG) test.

• Male subject agrees to use an acceptable method for contraception for the duration of the study.

• = 18 years of age at the time of registration.

• Patients must have adequate renal function as demonstrated by a serum creatinine < 1.5 mg/dl unless felt to be secondary to lymphoma.

• Must have an alanine aminotransferase (ALT)/aspartate aminotransferase (AST) = 3.5 the upper limit of normal and a total bilirubin = 2.0 mg/dL unless secondary to lymphoma.

• Must have a cardiac left ventricular ejection fraction = 50%.

• At least 1 measurable tumor mass (greater than 1.5 cm in the longest dimension and greater than 1.0 cm in the short axis).

• Eastern Cooperative Oncology Group (ECOG) performance status = 2.

Exclusion Criteria:

• Subject with primary or secondary central nervous system (CNS) lymphoma (current or previously treated) will not be eligible.

• A history of unrelated (non-lymphomatous) neoplasm within the past 10 years other than non-melanoma skin cancer or in-situ cervix cancer. Subjects with a prior diagnosis of malignancy more than 10 years may be entered into the study at the discretion of the Principal Investigator.

• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

• Patient has received other investigational drugs with 14 days before enrollment.

• Patient has hypersensitivity to boron or mannitol.

• Female subject is pregnant or breast-feeding. Chemotherapeutic agents are known to have teratogenic effects on developing embryos and to cause chromosomal damage to gametes. These agents also cause bone marrow suppression and can be excreted in milk. Confirmation that the subject is not pregnant must be established by a negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.

• Patient has = Grade 2 peripheral neuropathy within 14 days before enrollment.

• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.

• Patient has a platelet count of < 10 x 10¹°/L (unless due to bone marrow involvement with lymphoma documented within 14 days before enrollment).

• Patient has an absolute neutrophil count of < 1.0 x 10?/L (unless due to bone marrow involvement with lymphoma documented within 14 days before enrollment).

• Patient has a calculated or measured creatinine clearance of < 20 mL/minute within 14 days before enrollment.

• Presence of antibodies to HIV.

• Subject unwilling to give informed consent.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular

Intervention

Drug:
• Bortezomib
Bortezomib 1.6 mg/m² given on days 1 and 8

Biological:
• Rituximab
Rituximab 375 mg/m²

Drug:
• Doxorubicin
Doxorubicin 50 mg/m²
• Cyclophosphamide
Cyclophosphamide 750 mg/m²
• Vincristine
Vincristine 1.4 mg/m² (capped at 1.5 mg maximum) given on day 1
• Prednisone
Prednisone 100 mg/day given orally on days 1-5

Locations

Country	Name	City	State
United States	Emory University Winship Cancer Institute	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (2)

Cohen JB, Switchenko JM, Koff JL, Sinha R, Kaufman JL, Khoury HJ, Bumpers N, Colbert A, Hutchison-Rzepka A, Nastoupil LJ, Heffner LT, Langston AA, Lechowicz MJ, Lonial S, Flowers CR. A phase II study of bortezomib added to rituximab, cyclophosphamide, dox — View Citation

Sinha R, Kaufman JL, Khoury HJ Jr, King N, Shenoy PJ, Lewis C, Bumpers K, Hutchison-Rzepka A, Tighiouart M, Heffner LT, Lechowicz MJ, Lonial S, Flowers CR. A phase 1 dose escalation study of bortezomib combined with rituximab, cyclophosphamide, doxorubici — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal Tolerated Doses of Bortezomib and Vincristine When Used in Combination of Bortezomib, Rituximab and the CHOP Chemotherapy Regimen (Phase I)	INDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.	Cycle 1 for MTD, following completion of therapy for CR, up to 24 weeks	Yes
Secondary	An Estimate of the Overall Response Rate (ORR)(Complete Response [CR] + CR Unconfirmed [CRu] + Partial Response [PR]) to Bortezomib and Rituximab (VR)-CHOP According to International Workshop to Standardize Response Criteria (IWRC) Criteria		Following completion of therapy, up to 2 years	No