Study of Intensive Consolidation and Stem Cell Mobilization Therapy Followed by Autologous Stem Cell Transplantation in High-risk Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

This study is currently recruiting participants.
Verified January 2014 by University of California, San Francisco
Sponsor:
Collaborators:
University of California, San Francisco
GlaxoSmithKline
Information provided by (Responsible Party):
C. Babis Andreadis, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01555541
First received: March 9, 2012
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

The goal of this clinical trial is to show that incorporating ofatumumab instead of rituximab in combination with etoposide and cytarabine (OVA) is successful in collecting autologous stem cells for use in an autologous stem cell transplantation (autoSCT) and to examine its effectiveness in eliminating residual diffuse large B-Cell Lymphoma (DLBCL) in patients.


Condition Intervention Phase
Diffuse Large Cell Lymphoma Relapsed/Refractory
Drug: Ofatumumab
Drug: Etoposide
Drug: Cytarabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Intensive Consolidation and Stem Cell Mobilization Therapy With Ofatumumab, Etoposide, and High-dose Ara-C (OVA), Followed by Autologous Stem Cell Transplantation in High-risk Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Number of patients achieving complete response to the treatment upon successful stem cell mobilization [ Time Frame: Response evaluation will occur after salvage therapy, following intensive mobilization therapy (day 42) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to neutrophil and platelet engraftment following successful stem cell mobilization [ Time Frame: Response evaluation will occur at day +90 after ASCT, and at 6, 12 and 24 months thereafter ] [ Designated as safety issue: No ]
  • Progression free survival following treatment with Ofatumumab in combination with etoposide and high-dose ara-C (OVA) and subsequent autologous stem cell transplantation [ Time Frame: Response evaluation will occur at day +90 after ASCT, and at 6, 12 24, and 48 months thereafter. ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: June 2012
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single-arm study Drug: Ofatumumab
1000 mg IV days 0, 7, 14, 21
Other Names:
  • Arzerra
  • GSK1841157
  • HuMax-CD20
Drug: Etoposide
10 mg/Kg IV over 24 hours daily, days 1-4
Other Names:
  • Vespid®
  • VP-16
Drug: Cytarabine
2000 mg/m2 IV twice daily, days 1-4
Other Names:
  • Cytosar-U®
  • Ara-C
  • Cytosine arabinoside

Detailed Description:

Patients with relapsed Diffuse Large B-cell Lymphoma (DLBCL) who are refractory to or relapse within 12 months of first-line rituximab-based therapy, have poor outcomes with conventional approaches to autologous stem cell transplantation as detailed above. The investigators hypothesize that the intensive mobilization strategy developed can overcome some of the obstacles to successful autologous stem cell transplantation (ASCT) by both eliminating residual disease following salvage therapy and by facilitating stem cell collection. Even though there is clinical experience in the cooperative group setting with intensive pre-ASCT mobilization, it has never been prospectively validated in DLBCL and concerns exist as to its ability to improve outcomes with ASCT in this high-risk, and heavily pretreated group of patients. Furthermore, most patients in the study site's registry treated with intensive mobilization were rituximab-naïve and the findings may not translate in the rituximab-refractory population. The investigators also believe that ofatumumab, a novel monoclonal antibody against a distinct CD20 epitope may in fact overcome rituximab resistance in DLBCL patients and through more effective CDC may eliminate minimal residual disease in the patient and contaminating tumor cells in the stem cell graft.

General Design

This is a single-institution, single-arm, prospective phase II study. Patients with high-risk DLBCL (defined as either achieving less than complete remission (CR) to initial rituximab-containing therapy or relapsing within 12 months of initial therapy) will be enrolled on this study and will undergo staging prior to receiving intensive mobilization with ofatumumab, etoposide, and high-dose ara-C (OVA). Following successful stem cell collection, patients will proceed to standard autologous transplantation with cyclophosphamide, BCNU, and etoposide (CBV) preparative regimen. Response evaluation will occur after salvage therapy, following intensive mobilization therapy (d42), at day +90 after ASCT, and at 6, 12 and 24 months thereafter. Event-free, progression-free, and overall survival will also be assessed until 48 months. The primary study endpoint is mobilization-adjusted complete metabolic response rate (maCR) following OVA. Subjects who are not chemosensitive to salvage therapy (i.e. do not achieve a PR or CR) will be re-evaluated after an additional salvage regimen. If they are still not chemosensitive at this point, they will be withdrawn from the study and replaced.

  Eligibility

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

Inclusion Criteria:

  • Diagnosis of refractory or relapsed biopsy-proven CD20+ diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma.
  • Age 18 years or older
  • Refractory to or relapse following a rituximab/anthracycline first-line regimen
  • High-risk disease as defined by one of the following:

    • First relapse after CR within 12 months of initiation of front-line therapy
    • Less than CR to front-line therapy
    • sAAIPI of 1 or higher at the time of relapse
  • Receipt of no more than three prior chemotherapy regimens. Monoclonal antibody therapy alone and involved field radiotherapy are not included in this number. Prior use of ofatumumab is allowed if there has been no disease progression following that therapy (i.e. ofatumumab-based salvage regimens are allowed)
  • ECOG performance status ≤ 2.

Eligibility to proceed to OVA

  • Chemosensitive disease as defined by at least a partial response to salvage therapy by PET/CT criteria.
  • Bone marrow with less than 15% lymphoma cells following salvage therapy. No evidence of myelodysplasia.
  • Patients must have adequate organ function with serum creatinine <2.0 mg/dL, total bilirubin ≤2X ULN, and AST ≤3X ULN.
  • Neutrophils >1,000/μL and platelets >100,000/μL prior to day 0
  • No active uncontrolled infection.

Eligibility to proceed to CBV ASCT

  • Patients must be out of the hospital after OVA for a minimum of 4 weeks.
  • Adequate peripheral blood stem cell collection with CD34 cell dose ≥2 X 106 /kg (actual body weight).
  • No evidence of disease progression on day 42 assessment
  • Approved by the UCSF Bone Marrow Transplant Committee to proceed with ASCT.

Exclusion Criteria

  • Presence of disease transformation from a previously diagnosed low-grade lymphoma
  • Progression following prior ofatumumab-based therapy
  • Active central nervous system or meningeal involvement by lymphoma. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast MRI imaging for at least 3 months prior to study entry.
  • Evidence of myelodysplasia on any bone marrow biopsy.
  • Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half-lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study.
  • Other past or current malignancy. Subjects who have been free of malignancy for at least 3 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.
  • Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C.
  • History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
  • Known HIV infection
  • 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 extra systoles or minor conduction abnormalities.
  • Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.
  • Positive serology for Hepatitis B (HB) defined as a positive test for HbsAg and a detectable HBV DNA viral load. If negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded. If HBV DNA is negative, subject may be included but must undergo at least every 2-month HBV DNA PCR testing from the start of treatment during the treatment course. Prophylactic antiviral therapy may be initiated at the discretion of the investigator.
  • Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HCV PCR to confirm the result
  • Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening.
  • Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.
  • Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
  • Subjects who have received live virus vaccination within the 4 weeks prior to planned initiation of study treatment.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01555541

Contacts
Contact: Gerry Pelle-Day 415-476-4765 gpelle-day@cc.ucsf.edu
Contact: Sandra Jones 415-502-1564 JonesS1@cc.ucsf.edu

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94143
Principal Investigator: Charalambos Andreadis, MD, MSCE         
Sponsors and Collaborators
C. Babis Andreadis
University of California, San Francisco
GlaxoSmithKline
Investigators
Principal Investigator: Charalambos Andreadis, MD, MSCE University of California, San Francisco
  More Information

No publications provided

Responsible Party: C. Babis Andreadis, Assistant Clinical Professor, Department of Medicine, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01555541     History of Changes
Other Study ID Numbers: 112525
Study First Received: March 9, 2012
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
relapsed
refractory
DLBCL
lymphoma
B-cell
diffuse

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Etoposide phosphate
Etoposide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 16, 2014