POLA+BR for Relapsed or Refractory DLBCL

NCT04535102 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 19-1195.ccP30CA046934
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (10)

• Complete response at primary response

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

  3 weeks after last dose of study medication

• objective response at primary response

  assessment based on PET/CT as determined by the investigator

  3 weeks after last dose of study medication

• 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)

  2 years of follow up

• number of patients who underwent an ASCT

  Determined during follow up

  2 years of follow up

• Cell of Origin analysis

  Cell of origin analysis will be based on immunohistochemistry analysis

  2 years of follow up

• 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)

  2 years of follow up

• c-Myc status

  by FISH

  2 years of follow up

• 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

  2 years of follow up

• overall survival (OS)

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

  2 years of follow up

• 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.

  2 years of follow up

Study Arms (1)

Polatuzumab + BR (minimum 3 cycles)

EXPERIMENTAL

Patients 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

Drug: Polatuzumab Vedotin

Interventions

Polatuzumab Vedotin DRUG

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.

Polatuzumab + BR (minimum 3 cycles)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

polatuzumab vedotin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Brad Haverkos

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: September 1, 2020
• Study Start: January 29, 2021
• Primary Completion: March 17, 2022
• Study Completion: March 17, 2022
• Last Updated: May 9, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share