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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma

Thank you

Trial Information

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

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.

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

- 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.

Type of Study:


Study Design:

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

Outcome Measure:

Phase 1: Maximum tolerated dose (MTD) of brentuximab vedotin and bendamustine

Outcome Time Frame:

up to 1.5 years

Safety Issue:


Principal Investigator

Owen A O'Connor, MD, Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Columbia University


United States: Food and Drug Administration

Study ID:




Start Date:

July 2012

Completion Date:

August 2015

Related Keywords:

  • Hodgkin Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Hodgkin Lymphoma
  • Hodgkin Disease
  • Hodgkin's Disease
  • Anaplastic Large Cell Lymphoma
  • ALCL
  • SGN+Benda
  • Bendamustine
  • Brentuximab Vedotin
  • Hodgkin Disease
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Anaplastic



Columbia University Medical Center New York, New York  10032