Phase I/II Study of Bendamustine in Combination With Ofatumumab, Carboplatin and Etoposide

NCT01458366 | Completed Phase 1 Results DMC

• 3 other identifiers: 11D.4042011-61JT 2211
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The Phase I part of the study will apply to identify dose-limiting toxicities (DLT) and to define maximum-tolerated dose (MTD) for a new chemoimmunotherapy combination of bendamustine, ofatumumab, carboplatin, and etoposide in patients with Non Hodgkin's lymphoma whose disease has progressed or has recurred after prior chemotherapy. The Phase II part of the study will be a single-arm, open-label study in which all patients will receive combination bendamustine, ofatumumab, carboplatin and etoposide at the MTD dose defined in phase I. This study hopes to identify a life-prolonging therapy for patients with Non-Hodgkin's Lymphoma whose disease has progressed or has recurred after prior chemotherapy. The hypothesis is that the proposed combination of chemotherapy is well-tolerated and is efficacious for the treatment of relapsed/refractory aggressive B cell lymphomas.

Conditions

Non-Hodgkin's Lymphoma

Keywords

Non-Hodgkin's Lymphoma; Lymphoma; B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum-Tolerated Dose of Bendamustine in Combination With Ofatumumab, Carboplatin and Etoposide (BOCE)

  To determine the maximum-tolerated dose of bendamustine in combination with ofatumumab, carboplatin and etoposide for patients with refractory or relapsed aggressive B cell lymphomas. Toxicity levels will be assessed after every cycle until a dose-limiting toxicity (DLT) is found. Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria (CTCAE version 4.0). DLT will be defined as any grade 4 infection, or grade \>/= 3 non-hematologic toxicity that persists for 7 days or more.

  Baseline through 50 days

• Overall Frequency of Response With Combination of Bendamustine, Ofatumumab, Carboplatin, and Etoposide at Maximum Tolerated Dose (MTD)

  To determine the overall frequency of response with combination bendamustine, ofatumumab, carboplatin, and etoposide for refractory or relapsed aggressive B-cell lymphomas. Overall response is determined as cumulative Complete Response (CR) and Partial Response (PR).

  At 25 days and 3-8 weeks post-treatment

Secondary Outcomes (6)

• Phase I: Overall Frequency of Response

  CT and PET scans after Cycle 2 (approximately 25 days) and 3-8 weeks post-treatment

• Overall Complete Response (CR) and Partial Response (PR) Rate

  CT and PET scans after Cycle 2 (approximately 25 days) and 3-8 weeks post-treatment

• Overall Progression-Free Survival

  At 1 and 2 years after completion of treatment; year 2 reported

• Total Overall Survival for Transplant vs Non-transplant

  At 1 and 2 years after completion of treatment; year 2 reported

• Overall Proportion of Patients Who Are Able to Undergo Stem Cell Transplant (SCT)

  At 2 years after completion of treatment

Study Arms (5)

Bendamustine 70mg/m^2

EXPERIMENTAL

Level 1: Bendamustine 70mg/m\^2 Ofatumumab, Carboplatin, and Etoposide

Drug: Bendamustine; Drug: Ofatumumab; Drug: Carboplatin; Drug: Etoposide; Procedure: CT Scan; Procedure: PET Scan; Genetic: Stem Cell Transplant (STC)

Bendamustine 50mg/m^2

EXPERIMENTAL

Level -1: Bendamustine 50mg/m\^2 Ofatumumab, Carboplatin, and Etoposide

Drug: Bendamustine; Drug: Ofatumumab; Drug: Carboplatin; Drug: Etoposide; Procedure: CT Scan; Procedure: PET Scan; Genetic: Stem Cell Transplant (STC)

Bendamustine 90mg/m^2

EXPERIMENTAL

Level 2: Bendamustine 90mg/m\^2 Ofatumumab, Carboplatin, and Etoposide

Drug: Bendamustine; Drug: Ofatumumab; Drug: Carboplatin; Drug: Etoposide; Procedure: CT Scan; Procedure: PET Scan; Genetic: Stem Cell Transplant (STC)

Bendamustine 120mg/m^2

EXPERIMENTAL

Level 3: Bendamustine 120mg/m\^2 Ofatumumab, Carboplatin, and Etoposide

Drug: Bendamustine; Drug: Ofatumumab; Drug: Carboplatin; Drug: Etoposide; Procedure: CT Scan; Procedure: PET Scan; Genetic: Stem Cell Transplant (STC)

Phase II MTD

EXPERIMENTAL

Phase II: Bendamustine at MTD from Phase I, Ofatumumab, Carboplatin, and Etoposide

Drug: Bendamustine; Drug: Ofatumumab; Drug: Carboplatin; Drug: Etoposide; Procedure: CT Scan; Procedure: PET Scan; Genetic: Stem Cell Transplant (STC)

Interventions

Bendamustine DRUG

Phase 1: Given via IV at the following dose levels: * Level 1: 70 mg/m2 * Level -1: 50 mg/m2 * Level 2: 90 mg/m2 * Level 3: 120 mg/m2 Phase II: Given via IV on Days 1 and 2 of each cycle at the maximum-tolerated dose level found in the Phase I portion of the study.

Also known as: Ribomustin, Treanda, SDX-105

Bendamustine 120mg/m^2; Bendamustine 50mg/m^2; Bendamustine 70mg/m^2; Bendamustine 90mg/m^2; Phase II MTD

Ofatumumab DRUG

Phase II * Cycle 1: 300 mg via IV on Day 1 and 1000 mg via IV on Day 3 * Cycles 2 and 3: 1000 mg via IV on Day 1

Also known as: Arzerra, HuMax-CD20

Bendamustine 120mg/m^2; Bendamustine 50mg/m^2; Bendamustine 70mg/m^2; Bendamustine 90mg/m^2; Phase II MTD

Carboplatin DRUG

Phase II: AUC 5 via IV on Day 2 of each cycle

Also known as: cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II), Paraplatin, Paraplatin-AQ

Bendamustine 120mg/m^2; Bendamustine 50mg/m^2; Bendamustine 70mg/m^2; Bendamustine 90mg/m^2; Phase II MTD

Etoposide DRUG

Phase II: 100 mg/m2 via IV on Days 1, 2, and 3 of each cycle

Also known as: Etoposide phosphate, Eposin, Etopophos, Vepesid, VP-16

Bendamustine 120mg/m^2; Bendamustine 50mg/m^2; Bendamustine 70mg/m^2; Bendamustine 90mg/m^2; Phase II MTD

CT Scan PROCEDURE

CT Scan to assess disease after Cycle 2 (approximately 25 days) and 3-8 weeks post-treatment

Also known as: X-ray computed tomography

Bendamustine 120mg/m^2; Bendamustine 50mg/m^2; Bendamustine 70mg/m^2; Bendamustine 90mg/m^2; Phase II MTD

PET Scan PROCEDURE

PET Scan to assess disease after Cycle 2 (approximately 25 days) and 3-8 weeks post-treatment

Also known as: PET, Positron emission tomography

Bendamustine 120mg/m^2; Bendamustine 50mg/m^2; Bendamustine 70mg/m^2; Bendamustine 90mg/m^2; Phase II MTD

Stem Cell Transplant (STC) GENETIC

For potential transplant candidates: * Autologous STC: after 2 cycles of BOCE upon discretion of Thomas Jefferson University hematopoietic stem cell transplant group and in agreement with the study PI or her designee * Allogeneic STC: after 2 cycles of BOCE upon discretion of Thomas Jefferson University hematopoietic stem cell transplant group and in agreement with the study PI or her designee

Also known as: Stem Cell Transplant, Hematopoietic Stem Cell Transplantation, HSCT

Bendamustine 120mg/m^2; Bendamustine 50mg/m^2; Bendamustine 70mg/m^2; Bendamustine 90mg/m^2; Phase II MTD

Eligibility Criteria

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

You may qualify if:

• Age 18 and above
• Patients with histologically confirmed DLBCL, including primary mediastinal large B cell lymphoma, T cell rich B cell lymphoma, "double hit" DLBCL, mantle cell lymphoma, any transformed low grade B cell lymphomas or grade 3 follicular lymphoma (Grade 3a or 3b) who were refractory to RCHOP-like or any anthracycline based chemotherapy or relapsed after at least one prior combination chemotherapeutic regimen and who are deemed candidates for a salvage type chemotherapy.
• Relapsed disease:
• Progressive disease after a CR for at least 28 days. Progression will be defined according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007 (33)).
• Refractory disease (Subjects must meet one of the following criteria):
• Persistent or progressive lymphoma with a CR of \<28 days duration or with a PR of any duration. Subjects must have received at least 3 cycles of RCHOP-like or any anthracycline base chemotherapy or at least 2 full cycles of HyperCVAD-like chemotherapy.
• Persistent lymphoma and stable disease after at least 2 cycles of RCHOP-like or any anthracycline base chemotherapy or at least 1 full cycle of HyperCVAD-like chemotherapy (part A and B).
• Progressive disease despite at least 1 cycle of RCHOP-like or any anthracycline base chemotherapy or at least 1 cycle (part A or A and B) of HyperCVAD-like chemotherapy.
• Measurable disease, defined by the revised lymphoma criteria (Cheson 2007).
• Absolute neutrophil count ≥1,500 and platelet count ≥ 75,000, unless due to underlying lymphoma.
• Left ventricular ejection fraction estimated by MUGA scan or 2D-echocardiogram of at least 45% Cardiology consult is recommended prior to enrollment if a history of coronary artery disease, CHF with estimated LVEF of \<50% or clinically significant arrhythmia.
• Estimated glomerular filtration rate (GFR) must be ≥ 50 mL/min
• Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) unless deemed elevated secondary to lymphoma involvement of the liver or known Gilbert's syndrome.
• Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 × ULN; unless elevated secondary to lymphoma involvement of the liver
• Alkaline phosphatase ≤ 2.5 × ULN; unless elevated secondary to lymphoma involvement of the liver.

You may not qualify if:

• Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• Use of investigational agents within 4 weeks prior to enrollment.
• Any anticancer therapy within 3 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy.
• Radioimmunotherapy (i.e. Zevalin) within 8 weeks of enrollment.
• Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 4 weeks prior to start of therapy.
• Autologous stem cell rescue within 12 weeks before study enrollment or those who underwent allogeneic stem cell transplant within one year of enrolment.
• Known leptomeningeal or parenchymal brain involvement with lymphoma unless in complete remission after treatment for at least 12 weeks with negative CSF cytology within 2 weeks. Prophylaxis of CNS disease using intrathecal dosing of cytotoxic regimens is permitted and should be performed according to the discretion of the treating physician.
• History of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatment.
• Systemic fungal, bacterial, viral, or other infection if not controlled. Defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment. (May be enrolled if controlled on treatment).
• Significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms.
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extrasystoles or minor conduction abnormalities.
• Other malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy, with the following exceptions: treated non-melanoma skin cancer, any in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated, or radical prostatectomy or definitive prostate irradiation has been performed.
• Positive test for the Human Immunodeficiency Virus (HIV), unless undetectable viral load within 3 months of enrollment (HIV RNA less than 48 copies/mL) on HAART therapy.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• GlaxoSmithKline: collaborator
• Novartis: collaborator

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell

Interventions

Bendamustine Hydrochloride; ofatumumab; Carboplatin; Etoposide; etoposide phosphate; Tomography Scanners, X-Ray Computed; Magnetic Resonance Spectroscopy; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Equipment and Supplies; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Joanna Filicko-O'Hara, MD
• Organization: Sidney Kimmel Cancer Center at Thomas Jefferson University

Joanna.Filicko@jefferson.edu

215-503-7787

Study Officials

• Joanne Filicko-O'Hara, MD

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2011
• First Posted: October 24, 2011
• Study Start: November 9, 2011
• Primary Completion: August 27, 2018
• Study Completion: July 23, 2020
• Last Updated: April 30, 2025
• Results First Posted: March 24, 2020

Record last verified: 2025-04

Locations

US (1)