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Diffuse Large Cell Lymphoma Relapsed/RefractoryPhase 2NCT01555541

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

A Phase 2 study testing Ofatumumab, Etoposide and Cytarabine in people with Diffuse Large Cell Lymphoma Relapsed/Refractory, run by C. Babis Andreadis at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ofatumumab, Etoposide and Cytarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited States
Study dates
25 May 2012to 1 Jul 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • Second-line age-adjusted International Prognostic Index score (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)
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Eligibility to proceed to OVA
  • Chemosensitive disease as defined by at least a partial response to salvage therapy by positron emission tomography/computed tomography (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 ≤2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) ≤3 times the 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 cluster of differentiation 34 (CD34) cell dose ≥2 X 106 /kg (actual body weight).
  • No evidence of disease progression on day 42 assessment
  • Approved by the University of California, San Francisco (UCSF) Bone Marrow Transplant Committee to proceed with ASCT.

Who cannot join

  • 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 central nervous system (CNS) or meningeal involvement must be in a documented remission by cerebrospinal fluid (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.
Show all 17Show fewer
  • 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 hepatitis B virus (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 polymerase chain reaction (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 hepatitis C antibody (HCAb), in which case reflexively perform a hepatitis C virus (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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

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

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.

Read the 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 cluster of differentiation antigen 20 (CD20) epitope may in fact overcome rituximab resistance in DLBCL patients and through more effective complement dependent cytotoxicity (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, 1,3-bis(2-chloroethyl)-1-nitrosourea (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 partial response or complete response) 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.

Being tested
Ofatumumab, Etoposide, Cytarabine
Keywords
relapsed, refractory, DLBCL, lymphoma, B-cell, diffuse
Medical subject headings
Recurrence, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OfatumumabDrug

    Also called Arzerra, GSK1841157, HuMax-CD20

    1000 mg IV days 0, 7, 14, 21

  • EtoposideDrug

    Also called Vespid®, VP-16

    10 mg/Kg IV over 24 hours daily, days 1-4

  • CytarabineDrug

    Also called Cytosar-U®, Ara-C, Cytosine arabinoside

    2000 mg/m2 IV twice daily, days 1-4

Study groups in NCT01555541
Study groupRoleWhat they receive
Single-arm studyExperimentalNot described
Receives: Drug: Ofatumumab; Drug: Etoposide; Drug: Cytarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients Achieving Complete Response (CR) to the Treatment Upon Successful Stem Cell Mobilization

    CR will be calculated based on the PET/CT scan following 2 cycles of salvage therapy using the revised International Working Group (IWG) Criteria for a lymphoma response. This includes: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy, Post-treatment residual mass of any size is permitted as long as it is PET-, Spleen and/or liver, if enlarged before therapy based on physical exam or CT scan, should not be palpable on physical exam and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear, If bone marrow was involved by lymphoma before treatment, infiltrate must have cleared on repeat bone marrow biopsy. Biopsy sample must be adequate (with goal of > 20 mm unilateral core). If sample is indeterminate by morphology, it should be negative by immunohistochemistry. A sample that is negative by immunohistochemistry but demonstrates small population of clonal l

    Measured: Day 42

  2. Number of Patients Achieving Mobilization-adjusted Complete Response (maCR)

    Number of patients achieving maCR to the treatment upon successful stem cell mobilization, defined as at least 2 x10^6 cluster of differentiation 34 (CD34)+cells/Kg of actual body weight. Patients who require use of plerixafor or an autologous bone marrow harvest are considered mobilization failures and will be treated as non-responders.

    Measured: Day 42

Secondary outcomes (7)

  1. Number of Patients Who Received OVA and Then Met Criteria to Proceed to ASCT and Achieved a CR/Partial Response (PR) Post-ASCT

    Determination of CR or PR must meet the revised International Working Group (IWG) Criteria for lymphoma response

    Measured: Up to 5 months

  2. Number of Patients Who Advance From Partial Response (PR) to Complete (CR)

    Fluorodeoxyglucose-positron emission tomography (FDG-PET) conversion rate was used determined the number of participants who improved following OVA Treatment.

    Measured: Up to 5 months

  3. Number of Participants With Successful Neutrophil Engraftments

    Neutrophil engraftment is defined as the first day of 3 consecutive days with absolute neutrophil count of >500 cells/microlitre (uL). Response evaluation will occur at day +90 after ASCT, and at 6, 12 and 24 months thereafter

    Measured: Up to 24 months after ASCT

  4. Number of Participants With Successful Platelet Engraftments

    Platelet engraftment is defined as the first of three consecutive measurements for which the platelet count was > 20,000/uL, and must be at least 24 hours following the last platelet transfusion. Response evaluation will occur at day +90 after ASCT, and at 6, 12 and 24 months after ASCT

    Measured: Up to 24 months after ASCT

  5. Median Time to Progression

    Time to progression (TTP) is defined as the time from treatment after OVA until documented lymphoma progression or receipt of anti-lymphoma therapy (except for planned post-ASCT radiotherapy) or death due to lymphoma. Patients are to be censored at the time of last followup or death due to another cause

    Measured: Up to 48 months

  6. Progression Free Survival Rate

    The percentage of participants in the study still alive at time of censoring. The time frame defined as the time from day 0 of OVA treatment until lymphoma progression, receipt of anti-lymphoma therapy (except for planned post-ASCT radiotherapy), or death as a result of any cause. Patients will be censored at the time of median follow-up.

    Measured: Up to 24 months

  7. Overall Survival Rate (OS)

    The percentage of participants in the study still alive at time of censoring. The time frame is defined as the time from day 0 of OVA treatment until death as a result of any cause. Patients will be censored at the time of last followup

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2012 (estimated)
  2. Study start25 May 2012
  3. Primary completion6 Jul 2017
  4. Study completion1 Jul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01555541
Sponsor's protocol ID
112525
Other IDs
NCI-2012-00863
Status last verified
Jun 2022
First submitted
9 Mar 2012
Last updated
29 Jun 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Thiruvengadam SK, Hunter B, Varnavski A, Fakhri B, Kaplan L, Ai WZ, Pampaloni M, Huang CY, Martin T 3rd, Damon L, Andreadis CB. Ofatumumab, Etoposide, and Cytarabine Intensive Mobilization Regimen in Patients with High-risk Relapsed/Refractory Diffuse Large B-Cell Lymphoma Undergoing Autologous Stem Cell Transplantation. Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):246-256.e2. doi: 10.1016/j.clml.2020.11.005. Epub 2020 Nov 11.

    PubMed 33288485

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ofatumumab, Etoposide and Cytarabine in people with Diffuse Large Cell Lymphoma Relapsed/Refractory, run by C. Babis Andreadis at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Achieving Complete Response (CR) to the Treatment Upon Successful Stem Cell Mobilization (time frame: Day 42). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01555541, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2022.

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