Brentuximab Vedotin and Bendamustine for the Treatment of Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma (ALCL) (SGN + Benda)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Columbia University
Sponsor:
Collaborators:
British Columbia Cancer Agency
Princess Margaret Hospital, Canada
Information provided by (Responsible Party):
Owen A. O'Connor, Columbia University
ClinicalTrials.gov Identifier:
NCT01657331
First received: August 2, 2012
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

This is a Phase 1/2 multicenter study to assess the safety and effectiveness of brentuximab vedotin and bendamustine, when given together, in patients with Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma (ALCL) that has either returned or did not respond to initial treatment(s). Patients will be accrued at Columbia University Medical Center (CUMC) and at two subsites in Canada.

Brentuximab Vedotin will be given to patients on day 1 of each 21 day cycle and Bendamustine will be given to patients on days 1 AND 2 of each 21 day cycle. Days 3-21 will be for rest.


Condition Intervention Phase
Hodgkin Lymphoma
Anaplastic Large Cell Lymphoma
Drug: Adcetris
Drug: Bendamustine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Clinical Trial of the Combination of Brentuximab Vedotin and Bendamustine in Patients With Relapsed or Refractory Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Phase 1: Maximum tolerated dose (MTD) of brentuximab vedotin and bendamustine [ Time Frame: up to 1.5 years ] [ Designated as safety issue: Yes ]
  • Phase 1: Dose limiting toxicities (DLT) of brentuximab vedotin and bendamustine. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: Yes ]
  • Phase 2: Overall Response Rate (CR + PR) for the combination of brentuximab vedotin and bendamustine [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase 1: Progression free survival (PFS) and duration of response (DOR) for all patients. [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Phase 1: Overall response rate (ORR) (complete response (CR) + partial response (PR)) for all patients [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
  • Phase 2: Safety and tolerability of the combination of brentuximab vedotin and bendamustine [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Phase 2: Duration of response, Progression free survival and Overall Survival (OS) for the combination of brentuximab vedotin and bendamustine [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Serum Tarc levels in patients as a function of treatment with brentuximab vedotin and bendamustine. [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Level of peripheral blood lymphocyte expression of programmed death-1 (PD-1) as a function of treatment with brentuximab vedotin and bendamustine. [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Decline in serum levels of IL-10 and IL-6 as a function of treatment with brentuximab vedotin and bendamustine [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 71
Study Start Date: July 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Adcetris
    Dose escalation in phase I of the study from 1.2-1.8 mg/kg, IV infusions over 30 minutes on day 1 of each 21-day cycle.
    Other Names:
    • Brentuximab Vedotin
    • SGN35
    Drug: Bendamustine
    Dose escalation in phase I of the study from 60-100 mg/m2, IV infusion on days 1 and 2 of each 21-day cycle.
    Other Names:
    • Treanda
    • Bendamustine HCl
Detailed Description:

This is a phase 1/2 open label, multicenter study to assess the safety and efficacy of brentuximab vedotin in combination with bendamustine in patients with relapsed or refractory Hodgkin Lymphoma (HL) or other CD30+ expressing hematologic malignancies. Dose escalation in phase 1 will proceed according to a standard 3 + 3 dose escalation design. There will be no intracohort dose escalation. Three patients will be assigned to the starting dose level 1. If no dose limiting toxicities (DLT) are observed after one cycle of treatment, and if the start of cycle 2 treatment is not delayed greater than 7 days for any toxicity possibly related to drug, trial accrual proceeds to the next dose level and another cohort of 3 patients is enrolled. If 1 patient in a cohort experiences a DLT, then the cohort is expanded to 6, if 2 or more patients in this cohort experience a DLT then the dose level decreases. If none of the additional patients experience a DLT (1 out of 6) then dose escalation continues. The maximum tolerated dose (MTD) is defined as the highest dose level at which <33% of the dose cohort (0 of 3 or 1 of 6) experience a DLT in the first cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed relapsed or refractory HL or ALCL documented CD30+ expression from either original diagnosis or a tumor biopsy in the relapsed setting.
  • For patients with HL, subjects are eligible after failure or having declined autologous stem cell transplant or at least two prior multi-agent chemotherapy regimens if they are not autologous stem cell transplant candidates. For patients with ALCL, subjects are eligible after failure of at least one prior multi-agent chemotherapy regimen and if they are not eligible for or have declined autologous stem cell transplant.
  • Must have received first line chemotherapy. No upper limit for the number of prior therapies
  • Patients with prior autologous or allogeneic stem cell transplant are eligible as long as they meet all other criteria.
  • Measurable or evaluable disease, as defined in 2008 Revised Response Criteria for Malignant Lymphoma(33)
  • Age > 18 years
  • ECOG performance status 0,1 or 2
  • Patient's must have adequate organ and marrow function as defined below

    • Absolute neutrophil count > 1,000 (1.0 x 109/L)
    • Platelets > 50,000 (50 x 109/L)
    • Total Bilirubin < 1.5 x institutional limits unless documented Gilbert's syndrome (then <2.5 x institutional upper limit)
    • AST (SGOT)/ALT (SGPT) < 2.0 x institutional upper limit of normal (unless known hepatic involvement then < 3.5 x institutional upper limit)
    • Creatinine within normal institutional limits OR creatinine clearance > 50mL/min for patients with creatinine levels above institutional normal
    • If female of childbearing age, negative serum pregnancy test within 7 days prior to the first dose of brentuximab vedotin in this study
    • Must be willing to use contraception during the study, and for 30 days following the last dose of study drug.
    • Able to understand and to sign a written consent document

Exclusion Criteria:

  • Prior treatment with brentuximab vedotin and bendamustine in combination. May have received prior therapy with brentuximab vedotin or bendamustine separately.
  • Received either brentuximab vedotin or bendamustine within 3 months of receiving their first dose of protocol based therapy.
  • If brentuximab vedotin or bendamustine was previously received, had disease progression during the first 3 cycles of either brentuximab vedotin or bendamustine.
  • Systemic steroids that have not been stabilized to the equivalent of < 10 mg/day of prednisone 7 days prior to the initiation of the trial
  • ANY concurrent investigational agents
  • Exposure to chemotherapy, radiotherapy, biologics or investigational agents within 3 weeks prior enrollment in the study
  • Known cerebral or meningeal disease
  • Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy the patients must be disease free and off treatment for > 3 years.
  • Uncontrolled intercurrent illness including but not limited to: ongoing or active infection, systemic congestive heart failure Class III or IV by NYHA criteria, unstable angina pectoris, or cardiac arrhythmia, or in patients status post allogeneic transplantation with uncontrolled graft versus host disease (GVHD).
  • Pre-existing neuropathy grade III or greater
  • Pregnant or nursing
  • Known hypersensitivity to brentuximab vedotin, bendamustine, or mannitol
  • Known Human Immunodeficiency Virus (HIV) positive, or active hepatitis A, hepatitis B or hepatitis C; if hepatitis Bsurface antigen positive or Bcore antibody positive must have normal liver function tests and be willing and able to take anti-hepatitis medication such as lamivudine or equivalent.
  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: NCT01657331

Contacts
Contact: Molly Patterson mp2621@columbia.edu
Contact: Celeste Rojas cr2393@columbia.edu

Locations
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10022
Contact: Molly Patterson    212-326-5720    mp2621@columbia.edu   
Contact: Celeste Rojas    212-326-5720    cr2393@columbia.edu   
Principal Investigator: Owen A O'Connor, MD, Ph.D.         
Canada, British Columbia
British Columbia Cancer Agency Recruiting
Vancouver, British Columbia, Canada, V5z 4E6
Contact: Elena Moon    604-877-6000 ext 5981    emoon@bccancer.bc.ca   
Contact: Joseph Connors, MD    604-877-6000    jconnors@bccancer.bc.ca   
Principal Investigator: Joseph Connors, MD         
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada
Contact: Ruth Turner       Ruth.Turner@uhn.ca   
Principal Investigator: John Kuruvilla, MD         
Sponsors and Collaborators
Owen A. O'Connor
British Columbia Cancer Agency
Princess Margaret Hospital, Canada
Investigators
Principal Investigator: Owen A O'Connor, MD, Ph.D. Columbia University
  More Information

No publications provided

Responsible Party: Owen A. O'Connor, Professor of Medicine and Experimental Therapeutics, Director, Center for Lymphoid Malignancies, Columbia University
ClinicalTrials.gov Identifier: NCT01657331     History of Changes
Other Study ID Numbers: AAAJ5050
Study First Received: August 2, 2012
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Columbia University:
Hodgkin Lymphoma
Hodgkin Disease
Hodgkin's Disease
Anaplastic Large Cell Lymphoma
ALCL
SGN+Benda
Bendamustine
Brentuximab Vedotin

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, T-Cell
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies, Monoclonal
Bendamustine
Nitrogen Mustard Compounds
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014