Study of Brentuximab Vedotin Combined With RCHOP or RCHP in Front-line Treatment of Patients With Diffuse Large B-cell Lymphoma (DLBCL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Seattle Genetics, Inc.
Sponsor:
Information provided by (Responsible Party):
Seattle Genetics, Inc.
ClinicalTrials.gov Identifier:
NCT01925612
First received: August 15, 2013
Last updated: June 29, 2016
Last verified: June 2016
  Purpose

This study has 3 parts. The purpose of Part 1 of this study is to assess the safety and efficacy of brentuximab vedotin in combination with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) (known as BV+RCHOP) in patients with DLBCL that have never been treated. Patients will be randomly assigned in a 1:1 ratio to receive RCHOP together with 1 of 2 doses of brentuximab vedotin. Patients will be tested to see if there is a difference in side effects between the 2 groups.

The purpose of Part 2 of this study is to assess the safety and efficacy of brentuximab vedotin in combination with RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisone) (known as BV+RCHP) in patients with CD30-positive DLBCL that have never been treated. Patients will be enrolled to receive RCHP together with 1.8mg/kg of brentuximab vedotin.

The purpose of Part 3 of this study is to assess the safety and efficacy of BV+RCHP compared to standard RCHOP in patients with CD30-positive DLBCL that have never been treated. Patients will be randomly assigned in a 1:1 ratio to receive either BV+RCHP or RCHOP. Patients will be tested to see if there is a difference in side effects between the 2 groups.


Condition Intervention Phase
Lymphoma, B-cell
Lymphoma, Large B-cell, Diffuse
Drug: brentuximab vedotin
Drug: rituximab
Drug: vincristine
Drug: cyclophosphamide
Drug: prednisone
Drug: doxorubicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Brentuximab Vedotin in Combination With Standard of Care Treatment (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone [RCHOP]) or RCHP ( Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone) as Front-line Therapy in Patients With Diffuse Large B-cell Lymphoma (DLBCL)

Resource links provided by NLM:


Further study details as provided by Seattle Genetics, Inc.:

Primary Outcome Measures:
  • Complete remission rate [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • Incidence of adverse events [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
  • Incidence of laboratory abnormalities [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Objective response rate [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • Progression-free survivial [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 125
Study Start Date: August 2013
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: BV(1.2 mg/kg) + RCHOP
Brentuximab vedotin 1.2 mg/kg plus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone
Drug: brentuximab vedotin
1.2 mg/kg by IV infusion every 3 weeks for up to 6 cycles
Other Name: Adcetris, SGN-35
Drug: rituximab
375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Drug: vincristine
1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total)
Drug: cyclophosphamide
750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Drug: prednisone
100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles
Drug: doxorubicin
50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Experimental: Part 1: BV(1.8 mg/kg) + RCHOP
Brentuximab vedotin 1.8 mg/kg plus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone
Drug: brentuximab vedotin
1.8 mg/kg by IV infusion every 3 weeks for up to 6 cycles
Other Name: Adcetris, SGN-35
Drug: rituximab
375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Drug: vincristine
1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total)
Drug: cyclophosphamide
750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Drug: prednisone
100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles
Drug: doxorubicin
50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Experimental: Part 2: BV(1.8 mg/kg) + RCHP
Brentuximab vedotin 1.8 mg/kg plus rituximab, cyclophosphamide, doxorubicin, predisone
Drug: brentuximab vedotin
1.8 mg/kg by IV infusion every 3 weeks for up to 6 cycles
Other Name: Adcetris, SGN-35
Drug: rituximab
375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Drug: cyclophosphamide
750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Drug: prednisone
100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles
Drug: doxorubicin
50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Active Comparator: Part 3: RCHOP
Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone
Drug: rituximab
375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Drug: vincristine
1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total)
Drug: cyclophosphamide
750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Drug: prednisone
100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles
Drug: doxorubicin
50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Experimental: Part 3: BV(1.8 mg/kg) + RCHP
Brentuximab vedotin 1.8 mg/kg plus rituximab, cyclophosphamide, doxorubicin, prednisone
Drug: brentuximab vedotin
1.8 mg/kg by IV infusion every 3 weeks for up to 6 cycles
Other Name: Adcetris, SGN-35
Drug: rituximab
375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Drug: cyclophosphamide
750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
Drug: prednisone
100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles
Drug: doxorubicin
50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles

Detailed Description:

In the first part of this study, patients in the 2 groups were tested to see if there was a difference in the response to treatment and whether there were differences in the side effects (unwanted effects). After the sponsor and study doctors reviewed side effects in both dose levels, they noticed that patients in the higher dose of brentuximab vedotin had more problems with nerve function in their arms or legs (peripheral neuropathy). The patients receiving the lower dose of brentuximab vedotin did not report more problems with nerve function in their arms or legs (peripheral neuropathy) compared to the patients receiving the higher dose, so the higher dose is not being used anymore in combination with RCHOP and all patients will be treated with the lower dose.

The second and third parts of the study are being done to see if there are any side effects (unwanted effects) of the higher dose of brentuximab vedotin when combined with a modified version of RCHOP that omits vincristine, which may also cause peripheral neuropathy. The third part of the study is also being tested to see if there is a difference between BV+RCHP and RCHOP in the response to treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Treatment-naive patients with systemic de novo or transformed diffuse large B cell lymphoma (DLBCL) or follicular non-Hodgkin lymphoma (NHL) grade 3b
  • International Prognostic Index (IPI) score greater than or equal to 3 for patients greater than 60 years of age or age-adjusted IPI (aaIPI) score of 2 or 3 for patients less than or equal to 60 years of age
  • Stage IAX (bulk defined as single lymph node mass >10 cm in diameter), IB-IV disease
  • Measurable disease of at least 1.5 cm
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
  • Patients in Parts 2 and 3 must have histologically confirmed diagnosis of CD30-positive DLBCL

Exclusion Criteria:

  • Previous history of treated indolent lymphoma
  • History of another primary malignancy that has not been in remission for 3 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01925612

Contacts
Contact: Seattle Genetics Trial Information Support 866-333-7436 clinicaltrials@seagen.com

  Show 37 Study Locations
Sponsors and Collaborators
Seattle Genetics, Inc.
Investigators
Study Director: Katherine Ruffner Seattle Genetics, Inc.
  More Information

Responsible Party: Seattle Genetics, Inc.
ClinicalTrials.gov Identifier: NCT01925612     History of Changes
Other Study ID Numbers: SGN35-017 
Study First Received: August 15, 2013
Last Updated: June 29, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Seattle Genetics, Inc.:
Antibodies, Monoclonal
Antibody-Drug Conjugate
Antigens, CD30
Drug Therapy
Hematologic Diseases
Lymphoma, B-cell
Lymphoma, Large B-cell, Diffuse
Monomethyl auristatin E

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Doxorubicin
Prednisone
Vincristine
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 25, 2016