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

NCT01657331 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AAAJ5050
• Study Type: interventional
• Target: 71
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma

Keywords

Hodgkin Lymphoma; Hodgkin Disease; Hodgkin's Disease; Anaplastic Large Cell Lymphoma; ALCL; SGN+Benda; Bendamustine; Brentuximab Vedotin

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD) of brentuximab vedotin and bendamustine (phase 1)

  The highest dose that does not cause unacceptable side effects.

  Up to 1.5 years

• Dose limiting toxicities (DLT) of brentuximab vedotin and bendamustine (phase 1)

  A toxicity that prevents further administration of the agent at that dose level.

  Up to 1.5 years

• Overall Response Rate for the combination of brentuximab vedotin and bendamustine (phase 2)

  The percentage of subjects whose cancer shrinks or disappears after study treatment - Complete Response and Partial Response.

  Up to 3 years

Secondary Outcomes (3)

• Duration of Response (DoR) (phase 1)

  Up to 3 years

• Progression free survival (PFS) (phase 1)

  Up to 3 years

• Overall Survival (OS) (phase 2)

  Up to 3 years

Other Outcomes (3)

• Serum Tarc levels

  Up to 3 years

• Level of peripheral blood lymphocyte expression of programmed death-1 (PD-1)

  Up to 3 years

• Decline in serum levels of IL-10 and IL-6

  Up to 3 years

Study Arms (1)

Brentuximab Vedotin / Bendamustine

EXPERIMENTAL

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; Drug: Bendamustine; Drug: Neulasta

Interventions

Brentuximab Vedotin DRUG

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.

Also known as: Adcetris, SGN35

Brentuximab Vedotin / Bendamustine

Bendamustine DRUG

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.

Also known as: Treanda, Bendamustine HCl

Brentuximab Vedotin / Bendamustine

Neulasta DRUG

(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.

Also known as: pegfilgrastim

Brentuximab Vedotin / Bendamustine

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead

Study Sites (3)

Center for Lymphoid Malignancies at CUMC

New York, New York, 10010, United States

Location

British Columbia Cancer Agency

Vancouver, British Columbia, V5z 4E6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, Canada

Location

Related Publications (1)

• O'Connor OA, Lue JK, Sawas A, Amengual JE, Deng C, Kalac M, Falchi L, Marchi E, Turenne I, Lichtenstein R, Rojas C, Francescone M, Schwartz L, Cheng B, Savage KJ, Villa D, Crump M, Prica A, Kukreti V, Cremers S, Connors JM, Kuruvilla J. Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin's lymphoma: an international, multicentre, single-arm, phase 1-2 trial. Lancet Oncol. 2018 Feb;19(2):257-266. doi: 10.1016/S1470-2045(17)30912-9. Epub 2017 Dec 21.

  PMID: 29276022 DERIVED

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Large-Cell, Anaplastic

Interventions

Brentuximab Vedotin; Bendamustine Hydrochloride; pegfilgrastim

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Owen A O'Connor, MD, Ph.D.

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2012
• First Posted: August 6, 2012
• Study Start: July 1, 2012
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: July 17, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CA (2)