Clinical Trials /

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

NCT01555541

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Mediastinal Large B-Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Study of Intensive Consolidation and <span class="go-doc-concept go-doc-intervention">Stem Cell</span> Mobilization Therapy Followed by Autologous <span class="go-doc-concept go-doc-intervention">Stem Cell</span> Transplantation in High-risk Patients With Relapsed/Refractory Diffuse Large B-Cell <span class="go-doc-concept go-doc-disease">Lymphoma</span>

Title

  • Brief Title: 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
  • 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
  • Clinical Trial IDs

    NCT ID: NCT01555541

    ORG ID: 112525

    Trial Conditions

    Diffuse Large Cell Lymphoma Relapsed/Refractory

    Trial Interventions

    Drug Synonyms Arms
    Ofatumumab Arzerra, GSK1841157, HuMax-CD20 Single-arm study
    Etoposide Vespid, VP-16 Single-arm study
    Cytarabine Cytosar-U, Ara-C, Cytosine arabinoside Single-arm study

    Trial 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.

    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-nave 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.

    Trial Arms

    Name Type Description Interventions
    Single-arm study Experimental Ofatumumab, Etoposide, Cytarabine

    Eligibility 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/L and platelets >100,000/L 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of patients achieving complete response to the treatment upon successful stem cell mobilization

    Secondary Outcome Measures

    Time to neutrophil and platelet engraftment following successful stem cell mobilization

    Progression free survival following treatment with Ofatumumab in combination with etoposide and high-dose ara-C (OVA) and subsequent autologous stem cell transplantation

    Trial Keywords

    relapsed

    refractory

    DLBCL

    lymphoma

    B-cell

    diffuse