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

NCT00634179 | Completed Phase 1 Results DMC

• 2 other identifiers: IRB00002996X05215
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Lymphoma, B-Cell; Follicular Lymphoma

Keywords

Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• 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

Study Arms (1)

Treatment (VR-CHOP regimen)

EXPERIMENTAL

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. MAINTENANCE: Patients achieving complete response (CR) receive rituximab IV once every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or partial response (PR) receive rituximab IV and bortezomib once weekly for 4 weeks every 6 months for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib; Biological: Rituximab; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone

Interventions

Bortezomib DRUG

Bortezomib 1.6 mg/m² given on days 1 and 8

Also known as: Velcade

Treatment (VR-CHOP regimen)

Rituximab BIOLOGICAL

Rituximab 375 mg/m²

Also known as: Rituxin, MabThera

Treatment (VR-CHOP regimen)

Doxorubicin DRUG

Doxorubicin 50 mg/m²

Also known as: Adriamycin

Treatment (VR-CHOP regimen)

Cyclophosphamide DRUG

Cyclophosphamide 750 mg/m²

Also known as: Neosar

Treatment (VR-CHOP regimen)

Vincristine DRUG

Vincristine 1.4 mg/m² (capped at 1.5 mg maximum) given on day 1

Also known as: Oncovin

Treatment (VR-CHOP regimen)

Prednisone DRUG

Prednisone 100 mg/day given orally on days 1-5

Also known as: Deltasone

Treatment (VR-CHOP regimen)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 β-human chorionic gonadotropin (β-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 10¹⁰/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 10⁹/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.

Sponsors & Collaborators

• Emory University: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (2)

• 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, doxorubicin, modified vincristine, and prednisone for untreated follicular lymphoma and other low-grade B-cell lymphomas. Cancer. 2012 Jul 15;118(14):3538-48. doi: 10.1002/cncr.26660. Epub 2012 Jan 3.

  PMID: 22535574 RESULT

• 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, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma. Br J Haematol. 2015 Nov;171(4):539-46. doi: 10.1111/bjh.13637. Epub 2015 Aug 7.

  PMID: 26248505 RESULT

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma

Interventions

Bortezomib; Rituximab; Doxorubicin; Cyclophosphamide; Vincristine; Prednisone

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Christopher R. Flowers, MD, MS
• Organization: Emory University

crflowe@emory.edu

404-778-3935

Study Officials

• Christopher Flowers, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 11, 2008
• First Posted: March 12, 2008
• Study Start: February 1, 2008
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: October 27, 2016
• Results First Posted: March 15, 2016

Record last verified: 2016-09

Locations

US (1)