Polatuzumab Vedotin Plus Rituximab Ifosfamide Carboplatin and Etoposide (Pola-R-ICE) Versus R-ICE Alone in Second Line Treatment of Diffuse Large B-cell Lymphoma (DLBCL)

  • STATUS
    Recruiting
  • End date
    Dec 31, 2025
  • participants needed
    334
  • sponsor
    GWT-TUD GmbH
Updated on 20 July 2021

Summary

An open-label, prospective Phase III clinical study to compare polatuzumab vedotin plus rituximab, ifosfamide, carboplatin and etoposide (Pola-R-ICE) with rituximab, ifosfamide, carboplatin and etoposide (R-ICE) alone as salvage therapy in patients with primary refractory or relapsed diffuse large B-cell lymphoma (DLBCL)

Description

The study is designed as an international, multicenter, open-label, two-arm, prospective phase III study to compare the treatment of polatuzumab vedotin plus rituximab, ifosfamide, carboplatin and etoposide (Pola-R-ICE) with the combination of rituximab, ifosfamide, carboplatin and etoposide (R-ICE) alone as salvage therapy in patients with primary refractory or relapsed DLBCL.

The study will involve study sites in Germany, UK, Spain, and Austria. It is planned to include 324 patients who will be randomized 1:1 to receive either treatment in the experimental arm (Pola-R-ICE) or in the standard arm (R-ICE) to end up with 308 evaluable subjects for the randomized part of the trial. Further 10 patients will be treated with Pola-R-ICE during the safety run-in phase.

The study consists of a screening/inclusion visit, three chemotherapy cycles, an end-of - treatment visit (EoT), and follow-up visits. For each subject, the total duration of the study will be approximately 3 months of treatment plus at least 21 months follow-up. The study will end when the last included patient will have passed the last follow-up visit (LPLFU). For the study as a whole, the primary outcome will be evaluated when the last included patient will have completed the 21 months follow-up period or has left the study prematurely.

For the study as a whole, the primary outcome will be evaluated when the last included patient will have completed the 21 months follow-up period or has left the study prematurely.

Details
Condition Relapsed Diffuse Large B-cell Lymphoma, Refractory Diffuse Large B Cell Lymphoma
Treatment etoposide, ifosfamide, carboplatin, Polatuzumab Vedotin, MabThera
Clinical Study IdentifierNCT04833114
SponsorGWT-TUD GmbH
Last Modified on20 July 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

The informed consent form must be signed before any study specific tests or procedures are done
Adult male and female patients 18 years (16 years in the UK _) at the time of inclusion in the study (_ In the UK an "adult" means a person who has attained the age of 16 years, according to The Medicines for Human Use (Clinical Trials) Regulations 2004, Part 1 Point 2.)
Ability to understand and follow study-related instructions
Risk group: All patients with one of the following histologically defined entities: Histological diagnosis of primary refractory or relapsed aggressive B-cell non-Hodgkin lymphoma (B-NHL), confirmed by a biopsy of involved nodal or extranodal site. Patients with any of the following histologies can be included
DLBCL not otherwise specified (NOS)
T-cell/histiocyte-rich large B-cell lymphoma
Primary cutaneous DLBCL, leg type
Epstein-Barr virus (EBV)-positive DLBCL, NOS
DLBCL associated with chronic inflammation
Primary mediastinal (thymic) large B-cell lymphoma
High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
High-grade B-cell lymphoma, NOS
Refractory disease is defined as no complete remission to first line therapy
subjects who are intolerant to first line therapy are excluded. Three groups
of patients are
eligible
Progressive disease (PD) as best response to first line therapy (biopsy not mandatory if diagnostic sample available)
Stable disease (SD) as best response after at least 4 cycles of first line therapy (e.g., 4 cycles of R-CHOP) (biopsy not mandatory if diagnostic sample available)
Partial response (PR) as best response after at least 6 cycles, and biopsy-proven residual disease or disease Progression after the partial response
Relapsed disease is defined as complete remission to first line therapy
followed by biopsy proven disease relapse
\. Performance Status ECOG 0-2 at time of randomization or ECOG 3 at
screening if this is DLBCL-related and has improved to ECOG 2 or less with a
-day steroid treatment during the screening Phase (e.g. 1 mg/kg prednisone)
\. Information on all 5 International Prognostic Index (IPI) factors
\. Staging (PET-CT based-staging according to Lugano criteria 2014). Patients
must have PET-positive lesions
\. Subjects must have received adequate first line therapy including at a
minimum: i) anti-CD20 monoclonal antibody unless Investigator determines that
tumor is CD20 negative, and ii) an anthracycline containing chemotherapy
Regimen
\. Intent to proceed to high-dose therapy (HDT) and stem cell transplantation
(SCT) if response to second line therapy
\. Adequate hematological function, as defined by: hemoglobin 8 g/dL
absolute neutrophil count (ANC) 1.0 x 109/L OR 0.5 x 109/L if neutropenia is
attributable to underlying disease and before the administration of steroids
and platelet count 75 x 109/L OR 50 x 109/L if thrombocytopenia is
attributable to Underlying disease
\. Women of childbearing potential must have a negative pregnancy test
result within 7 days prior to the first study drug Administration
\. For women of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraceptive measures, and
agreement to refrain from donating eggs
\. For men: agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures, and agreement to refrain from
donating sperm

Exclusion Criteria

(1) Serious accompanying disorder leading to impaired organ function causing
significant clinical problems and reduced life expectancy of less than 3
months. In particular, patients with the following organ dysfunction caused by
accompanying disorders are to be
excluded
Heart failure with left ventricular ejection fraction (LVEF) < 45%
Impaired pulmonary function with vital capacity (VC) or forced expiratory volume (FEV1) < 50% of normal (only in case of history of significant pulmonary disease)
Impaired renal function with glomerular filtration rate (GFR) < 50 mL/min (calculated)
Impaired liver function with alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) or Bilirubin > 1.5 x upper limit of normal (ULN). If elevation is caused by the disease, threshold of 2.5 x ULN is accepted
Peripheral neuropathy > Grade II (2) Human immunodeficiency virus (HIV)-positivity with detectable viral load and/or a CD4+ count below 0.3/nL
(3) Hepatitis B and C as defined by seropositivity (HBsAG and anti HBe/ anti
HBc; anti-Hc); in case of false positive serology (transfused antibodies)
negative PCR-results will allow patient inclusion. 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
(4) Known active bacterial, viral, fungal, mycobacterial, parasitic, or other
infection (excluding fungal infections of nail beds) at study inclusion or any
unresolved major episode of infection (as evaluated by the investigator)
within 1 week prior to Cycle 1 Day 1
(5) Patients with suspected or latent tuberculosis. Latent tuberculosis needs
to be confirmed by positive interferon-gamma release Assay
(6) Primary or secondary central nervous system (CNS) lymphoma at the time of
recruitment
(7) Richter's transformation or prior chronic lymphocytic leukemia (CLL)
(8) Vaccination with a live vaccine within 4 weeks prior to Treatment
(9) Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1)
other than for diagnosis
(10) Treatment with radiotherapy, chemotherapy, immunotherapy
immunosuppressive therapy, or any investigational agent for the purposes of
treating cancer within 2 weeks prior to Cycle 1 Day 1
(11) Received more than one line of therapy for DLBCL
(12) Received polatuzumab vedotin as part of the first line therapy
(13) 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
(14) Ongoing treatment or study procedures within any other Investigational
Medicinal Product (IMP) clinical trial with the exception of follow-up. In
case of a preceding clinical trial, last application of the respective IMP(s)
must have been done more than five elimination half-lives before start of
study medication in this trial
(15) History of severe allergic or anaphylactic reactions to human, humanized
chimeric, or murine monoclonal antibodies
(16) History of hypersensitivity to any of the study drugs or their
ingredients or to drugs with similar structure
(17) Contraindications according to the Investigators Brochure (IB) of
polatuzumab vedotin or the local Summary of Product Characteristics (SmPCs) of
the used rituximab, ifosfamide, carboplatin or etoposide products
(18) Criteria which in the opinion of the investigator preclude participation
for scientific reasons, for reasons of compliance, or for reasons of the
subject's Safety
(19) Pregnancy or breastfeeding, or intending to become pregnant during the
study or within 12 months after the last dose of study drug
(20) Close affiliation with the investigator (e.g. a close relative) or
persons working at the study site
(21) Subject is an employee of the sponsor or involved Contract Research
Organization
At study inclusion, any organ impairment due to lymphoma infiltration is NOT
regarded as an exclusion criterion
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