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 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 112525NCI-2012-00863
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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 diffuse large B-Cell Lymphoma (DLBCL) in patients.

Conditions

Diffuse Large Cell Lymphoma Relapsed/Refractory

Keywords

relapsed; refractory; DLBCL; lymphoma; B-cell; diffuse

Outcome Measures

Primary Outcomes (2)

• 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

  Day 42

• 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.

  Day 42

Secondary Outcomes (7)

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

  Up to 5 months

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

  Up to 5 months

• Number of Participants With Successful Neutrophil Engraftments

  Up to 24 months after ASCT

• Number of Participants With Successful Platelet Engraftments

  Up to 24 months after ASCT

• Median Time to Progression

  Up to 48 months

Study Arms (1)

Single-arm study

EXPERIMENTAL

Drug: Ofatumumab; Drug: Etoposide; Drug: Cytarabine

Interventions

Ofatumumab DRUG

1000 mg IV days 0, 7, 14, 21

Also known as: Arzerra, GSK1841157, HuMax-CD20

Single-arm study

Etoposide DRUG

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

Also known as: Vespid®, VP-16

Single-arm study

Cytarabine DRUG

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

Also known as: Cytosar-U®, Ara-C, Cytosine arabinoside

Single-arm study

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• C. Babis Andreadis: lead
• University of California, San Francisco: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• 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.

  PMID: 33288485 BACKGROUND

MeSH Terms

Conditions

Recurrence; Lymphoma

Interventions

ofatumumab; Etoposide; Cytarabine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The study closed early due to low accrual

Results Point of Contact

• Title: Charalambos Andreadis, MD, MSCE, Associate Professor of Clinical Medicine
• Organization: University of California, San Francisco

cancertrials@ucsf.edu

877-827-3222

Study Officials

• Charalambos Andreadis, MD, MSCE

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Clinical Professor, Department of Medicine

Study Record Dates

• First Submitted: March 9, 2012
• First Posted: March 15, 2012
• Study Start: May 25, 2012
• Primary Completion: July 6, 2017
• Study Completion: July 1, 2021
• Last Updated: June 29, 2022
• Results First Posted: May 17, 2019

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)