AzTrials
AzTrials

Diffuse Large B Cell LymphomaPhase 2NCT04535102

POLA+BR for Relapsed or Refractory DLBCL

A Phase 2 study testing Polatuzumab Vedotin in people with Diffuse Large B Cell Lymphoma, run by University of Colorado, Denver.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

This is a phase II multicenter, open-label study of polatuzumab vedotin administered by IV infusion in combination with standard doses of bendamustine (B) and rituximab (R) in transplant-eligible patients with relapsed or refractory DLBCL. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B Cell Lymphoma
What is being tested?
Polatuzumab Vedotin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
29 Jan 2021to 17 Mar 2022
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Signed ICF
  • Age ≥ 18 years
  • Able to comply with the study protocol, in the investigator's judgment
  • Histologically confirmed DLBCL (Obtaining pathology samples is not required prior to enrollment, but confirmation of availability is required prior to enrollment)
  • Must have received at least one prior rituximab containing chemotherapy therapy for DLBCL.
  • Patients must be transplant-eligible and have either relapsed or have become refractory to a prior regimen.
Show all 30Show fewer
  • The following DLBCL histologies would be considered eligible for study entry:
  • o DLBCL, not otherwise specified (NOS) (including both GCB type and ABC type)
  • T-cell/histiocyte-rich large B-cell lymphoma
  • High-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements
  • High grade B-cell lymphoma, NOS
  • Primary mediastinal (thymic) large B-cell lymphoma
  • Epstein Barr virus positive DLBCL, NOS
  • HHV8-positive DLBCL, NOS
  • HIV positive DLBCL
  • At least one bi-dimensionally measurable lesion on imaging scan defined as > 1.5 cm in its longest dimension
  • Life expectancy of at least 24 weeks
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
  • Adequate hematologic function unless inadequate function is due to underlying disease, such as extensive bone marrow involvement or hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator. Adequate hematologic function is defined as follows:
  • o Hemoglobin ≥ 9 g/dL
  • o ANC ≥ 1.0 x 10g/L
  • o Platelet count ≥ 75 x 10g/L
  • For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea and age > 45 years) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or to use single highly effective or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for ≥ 12 months after the last dose of rituximab.
  • Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Examples of highly effective contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of < 1% per year. Barrier methods must always be supplemented with the use of a spermicide.
  • For women of childbearing potential, a negative serum pregnancy test result within 7 days prior to commencement of dosing. Women who are considered not to be of childbearing potential are not required to have a pregnancy test.
  • For men, agreement to remain abstinent or to use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of study drug and agreement to refrain from donating sperm during this same period.
  • Men with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy.
  • Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Male patients considering preservation of fertility should bank sperm before treatment with polatuzumab vedotin.

Who cannot join

  • History of severe allergic or anaphylactic reactions to humanized or murine MAbs (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
  • Contraindication to bendamustine or rituximab.
  • History of sensitivity to mannitol (mannitol is an excipient in bendamustine).
  • Prior use of any monoclonal antibody (MAb), radioimmunoconjugate, or antibody drug conjugate (ADC) within 5 half-lives or 4 weeks, whichever is longer, before Cycle 1 Day 1.
  • Treatment with chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1 Day 1. Radiotherapy for palliative relief of symptoms is allowed.
  • All acute, clinically significant treatment-related toxicity from prior therapy, except for alopecia, must have resolved to Grade ≤ 2 prior to Cycle 1 Day 1.
Show all 33Show fewer
  • Ongoing corticosteroid use > 30 mg/day prednisone or equivalent, for purposes other than lymphoma symptom control. Patients receiving corticosteroid treatment ≤ 30 mg/day prednisone or equivalent must be documented to be on a stable dose prior to study enrollment and initiation of therapy (Cycle 1 Day 1).
  • Ineligibility for ASCT (determined by investigator per local institutional practice)
  • Prior ASCT
  • History of transformation of indolent disease to DLBCL
  • Active CNS lymphoma. (Previously treated CNS disease is allowed)
  • Current Grade > 1 peripheral neuropathy
  • History of other malignancy that could affect compliance with the protocol or interpretation of results. Exceptions include, but are not limited to:
  • Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix or ductal carcinoma in situ of the breast at any time prior to the study are eligible.
  • A patient with any other malignancy that has been treated with curative intent and the malignancy has been in remission without treatment for > 3 years prior to enrollment is eligible.
  • Patients with low-grade, early-stage prostate cancer with no requirement for systemic therapy at any time prior to study are eligible.
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm).
  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1 Day 1.
  • Patients with suspected or latent tuberculosis. • Latent tuberculosis should be confirmed according to local testing requirements.
  • Positive test results for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen [HBsAg] serology).
  • Patients with occult or prior HBV infection (defined as negative HBsAg and positive hepatitis B core antibody [HBcAb]) may be included if HBV DNA is undetectable, provided that they are willing to undergo DNA testing on day 1 of every cycle and monthly for at least 12 months after the last cycle of study treatment and are willing to get prophylaxis with lamuvidine or entecavir for 6 months post immunosuppressive therapy. Patients who have protective titers of hepatitis B surface antibody (HBsAb) after vaccination or prior but cured hepatitis B are eligible.
  • Patients who are positive for Hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
  • Positive test results for uncontrolled HIV infection.
  • For patients with controlled HIV status (Positive HIV antibody, on Antiretroviral therapy with stable HIV viral load) are eligible.
  • Known infection human T-cell leukemia virus 1 (HTLV-1) virus. 21. Vaccination with a live vaccine within 28 days prior to treatment.
  • 22. Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1) other than for diagnosis.
  • 23. Women who are pregnant or lactating or who intend to become pregnant within a year of the last dose of study treatment in the rituximab cohorts or within 18 months of the last dose of study treatment in the obinutuzumab cohort
  • 24. Any of the following abnormal laboratory values, unless abnormal laboratory values are due to underlying lymphoma per the investigator:
  • Creatinine > 1.5 x upper limit of normal (ULN) or a measured creatinine clearance < 40 mL/min • AST or ALT > 2.5 x ULN
  • Total bilirubin ≥ 1.5 x ULN. Patients with documented Gilbert disease may be enrolled if total bilirubin is ≤ 3 x ULN
  • INR or PT > 1.5 x ULN in the absence of therapeutic anticoagulation
  • PTT or aPTT > 1.5 x ULN in the absence of a lupus anticoagulant
  • 25. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications

About this study

Official title: POLATUZUMAB PLUS BENDAMUSTINE PLUS RITUXIMAB (POLA+BR) AS SALVAGE THERAPY PRIOR TO AUTOLOGOUS STEM CELL TRANSPLANT FOR PATIENTS WITH RELAPSED OR PRIMARY REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA

This is a phase II multicenter, open-label study of polatuzumab vedotin administered by IV infusion in combination with standard doses of bendamustine (B) and rituximab (R) in transplant-eligible patients with relapsed or refractory DLBCL. A total of 22 patients will be enrolled over a period of 2 years through the University of Colorado and additional study sites if applicable. Study treatment will be given in 21-day cycles for patients with DLBCL.

Read the detailed description

The first day of treatment will constitute Cycle 1 Day 1. Patients will be treated with a minimum of three cycles and up to a maximum of 6 cycles to optimize responses prior to ASCT based on investigator discretion.

All patients will be evaluated for safety and efficacy according to the schedules of assessments.

All patients will be assessed for response to treatment by the investigator with the use of standard criteria according to the Modified Lugano Response Criteria at the following time points:

  • At the time of screening
  • At the time of primary response assessment (3 weeks after completion of study treatment (i.e., 3 weeks after Cycle 3 Day 1 or after last dose of study medication)

Imaging at these timepoints must include FDG-PET (18F-fluorodeoxyglucose-positron emission tomography) and a diagnostic-quality CT scan with both oral and IV contrast. A combined PET/CT scan is encouraged if feasible. CT scans with oral and IV contrast should include neck, chest, abdomen, and pelvic scans. In patients for whom contrast is contraindicated, (e.g., patients with contrast allergy or impaired renal clearance or patient denial), PET-CT scans without contrast are permitted so long as they permit consistent and precise measurement of target lesions during the study treatment period.

Patients will also be evaluated every 3 months for 2 years, or until disease progression, death, withdrawal of consent, or initiation of another anti-cancer therapy. Tumor assessments should also be performed to confirm clinical suspicion of relapse or disease progression for documentation. The study will end when all patients enrolled have been followed until death, have withdrawn consent, have been lost to follow-up, until 2-year follow up, or the Sponsor-investigator decides to end the trial, whichever occurs first.

Being tested
Polatuzumab Vedotin
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • Polatuzumab VedotinDrug

    Polatuzumab vedotin is an ADC designed for the targeted delivery of MMAE(mono-methyl auristatin E), a potent microtubule inhibitor to lymphoma cells expressing CD79b. MMAE has a mechanism of action that is similar to that of vincristine.

Study groups in NCT04535102
Study groupRoleWhat they receive
Polatuzumab + BR (minimum 3 cycles)ExperimentalPatients will be treated with a minimum of 3 cycles up to a maximum six cycles to optimize response prior to ASCT (stem cell transplant) per investigator discretion
Receives: Drug: Polatuzumab Vedotin

What is being measured

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

  1. Complete response at primary response

    The assessment is based on PET/CT, as determined by the investigator

    Measured: 3 weeks after last dose of study medication

  2. objective response at primary response

    assessment based on PET/CT as determined by the investigator

    Measured: 3 weeks after last dose of study medication

  3. duration of response (DOR) of combination therapy

    DOR, defined as the time from the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause based on PET/CT or CT only as determined by the investigator assessment.Response assessment will be determined according to Modified Lugano Response Criteria for Malignant Lymphoma (Lugano Classification)

    Measured: 2 years of follow up

  4. number of patients who underwent an ASCT

    Determined during follow up

    Measured: 2 years of follow up

  5. Cell of Origin analysis

    Cell of origin analysis will be based on immunohistochemistry analysis

    Measured: 2 years of follow up

  6. Differences in response rates based on timing of relapse

    <12 months of front-line R-chemotherapy versus >12 months after front-line R-chemotherapy and bulky disease prior to ASCT (bulk defined as mass > 7.5 cms)

    Measured: 2 years of follow up

  7. c-Myc status

    by FISH

    Measured: 2 years of follow up

  8. 2-yr progression free survival (PFS)

    PFS, defined as the time from date of first treatment to the first occurrence of progression or relapse, or death from any cause, based on PET/CT or CT only as determined by the investigator assessment

    Measured: 2 years of follow up

  9. overall survival (OS)

    defined as the time from the date of randomization or first treatment to the date of death from any cause

    Measured: 2 years of follow up

  10. stem cell collection failure rate

    Stem cells will be collected post primary response assessment. If patients achieve a PR after 3 cycles of Pola+BR and investigator decides to give additional cycles of Pola+BR (up to a max of 6 cycles) then stem cell collection may occur between cycles to minimize the chances of collection failure.

    Measured: 2 years of follow up

Timeline

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

  1. First posted1 Sep 2020
  2. Study start29 Jan 2021
  3. Primary completion17 Mar 2022
  4. Study completion17 Mar 2022

Why it stopped: Lack of sufficient patient population

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04535102
Sponsor's protocol ID
19-1195.cc
Other IDs
P30CA046934
Status last verified
May 2022
First submitted
23 Jul 2020
Last updated
9 May 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Polatuzumab Vedotin in people with Diffuse Large B Cell Lymphoma, run by University of Colorado, Denver.

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 30 inclusion and 33 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: withdrawn, as of the sponsor's last update on 9 May 2022. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Complete response at primary response (time frame: 3 weeks after last dose of study medication). The study lists 10 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 NCT04535102.

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 9 May 2022; AzTrials last refreshed its copy on 26 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in