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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Owen A. O'Connor, Columbia University
ClinicalTrials.gov Identifier:
NCT01657331
First received: August 2, 2012
Last updated: May 18, 2017
Last verified: May 2017
  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.

Condition Intervention Phase
Hodgkin Lymphoma
Anaplastic Large Cell Lymphoma
Drug: Brentuximab Vedotin
Drug: Bendamustine
Drug: Neulasta
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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 Owen A. O'Connor, Columbia University:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of brentuximab vedotin and bendamustine (phase 1) [ Time Frame: Up to 1.5 years ]
    The highest dose that does not cause unacceptable side effects.

  • Dose limiting toxicities (DLT) of brentuximab vedotin and bendamustine (phase 1) [ Time Frame: Up to 1.5 years ]
    A toxicity that prevents further administration of the agent at that dose level.

  • Overall Response Rate for the combination of brentuximab vedotin and bendamustine (phase 2) [ Time Frame: Up to 3 years ]
    The percentage of subjects whose cancer shrinks or disappears after study treatment - Complete Response and Partial Response.


Secondary Outcome Measures:
  • Duration of Response (DoR) (phase 1) [ Time Frame: Up to 3 years ]
    Time from documentation of tumor response to disease progression.

  • Progression free survival (PFS) (phase 1) [ Time Frame: Up to 3 years ]
    The length of time during and after the study treatment that a subject lives with the disease but it does not get worse.

  • Overall Survival (OS) (phase 2) [ Time Frame: Up to 3 years ]
    The length of time from either the date of diagnosis or the start of study treatment that subjects diagnosed with the disease are still alive.


Other Outcome Measures:
  • Serum Tarc levels [ Time Frame: Up to 3 years ]
    This is designed to measure the response to study treatment if the level declines.

  • Level of peripheral blood lymphocyte expression of programmed death-1 (PD-1) [ Time Frame: Up to 3 years ]
    The level will be evaluated as a function of response to therapy with brentuximab vedotin and bendamsutine.

  • Decline in serum levels of IL-10 and IL-6 [ Time Frame: Up to 3 years ]
    The decline will be evaluated as a function of response to therapy with brentuximab vedotin and bendamsutine.


Enrollment: 71
Actual Study Start Date: July 2012
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Brentuximab Vedotin / Bendamustine
Subjects with relapsed or refractory Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma will receive Brentuximab Vedotin in combination with Bendamustine, and prophylactic Neulasta
Drug: Brentuximab Vedotin
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:
  • Adcetris
  • 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
Drug: Neulasta
(Non-experimental) Standard procedure prophylactic pegfilgrastim on day 3 of any subsequent cycle after cycle 1, or filgrastim for 5 to 10 days, per investigator's discretion.
Other Name: pegfilgrastim

Detailed Description:
Brentuximab vedotin will be administered as an outpatient IV infusion on day 1 of each 21-day cycle. Bendamustine will be given as an outpatient infusion on days 1 and 2 of a 21-day cycle. Patients may receive prophylactic pegfilgrastim on day 3 of each cycle, or filgrastim for 5 to 10 days, per investigator's discretion. Patients can receive a maximum of 6 cycles of therapy.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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 > or = 18 years
  • ECOG performance status 0,1 or 2
  • Patient's must have adequate organ and marrow function as defined below

    • Absolute neutrophil count > or = 1,000 (1.0 x 109/L)
    • Platelets > or = 50,000 (50 x 109/L)
    • Total Bilirubin < or = 1.5 x institutional limits unless documented Gilbert's syndrome (then < 2.5 x institutional upper limit)
    • AST (SGOT)/ALT (SGPT) < or = 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 > or = 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 > or = 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 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

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10019
Canada, British Columbia
British Columbia Cancer Agency
Vancouver, British Columbia, Canada, V5z 4E6
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada
Sponsors and Collaborators
Owen A. O'Connor
Investigators
Principal Investigator: Owen A O'Connor, MD, Ph.D. Columbia University
  More Information

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: May 18, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Owen A. O'Connor, Columbia University:
Hodgkin Lymphoma
Hodgkin Disease
Hodgkin's Disease
Anaplastic Large Cell Lymphoma
ALCL
SGN+Benda
Bendamustine
Brentuximab Vedotin

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

ClinicalTrials.gov processed this record on May 25, 2017