Phase II Study With Ga101-DHAP as Induction Therapy in Relapsed/Refractory DLBCL Patients

NCT02374424 | Terminated Phase 2

• 1 other identifier: FIL_GA101_DHAP
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 10

Brief Summary

Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL.

Conditions

Diffuse, Large B-Cell, Lymphoma

Outcome Measures

Primary Outcomes (1)

• Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL.

  Primary objective is to assess whether the treatment achieves an absolute increase of the CR proportion of at least 20% (from 30% to 50%) with respect to the standard treatment. The complete response rate (CR) evaluated by PET scan after four cycles of GA101-DHAP before ASCT according to Cheson criteria.

  4 months

Secondary Outcomes (6)

• Overall Response Rate (ORR) prior to consolidation with BEAM and ASCT

  2 years

• Progression free survival (PFS) at 6 month after the end of treatment (EOT)

  6 month

• Overall Survival (OS) at 2 years after the EOT

  2 years

• Toxicity: Severe, life-threatening, fatal (grade 3, 4 and 5) and/or serious adverse events

  2 years

• The hematopoietic cell mobilization

  2 years

Study Arms (1)

GA101_DHAP

EXPERIMENTAL

Patients receive: GA101-DHAP x 2, restaging, mobilization and collection of peripheral blood stem cells, + GA101-DHAP x 2, restaging with PET and CT and consolidation with BEAM and ASCT in patients in response (CR+PR). During the treatment period of four cycles, all patients will receive a total of four 28-day courses of chemotherapy.

Drug: GA101_DHAP

Interventions

GA101_DHAP DRUG

Aim of the study is to assess whether the addition of GA101 to DHAP is more promising than standard R-DHAP, as induction therapy before high dose chemotherapy BEAM with ASCT with respect to response. Scheme of treatment: * GA101 1000 mg iv day 1, 8, 15 on first cycle (starting from cycle 2, GA101 1000 mg day 1) * Cisplatin 100 mg/sqm iv day 1 of every cycles in 24-hours infusion * Cytarabine 2000 mg/sqm in 3-hours infusion every 12 hours iv day 2 of every cycles * Dexamethasone 40 mg day 1-4 of every cycles * Pegfilgrastim 6 mg sc single dose 24 hours after the end of chemotherapy or G-CSF from day 4 till stem cell harvest during mobilization's course (II o III cycle GA101-DHAP) * GA101 1000 mg iv 24 hours before apheresis as purging in vivo during second courses of therapy

GA101_DHAP

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ Age \< 65
• Relapsed/refractory disease after receiving one line of standard R-CHOP like chemotherapy
• Diffuse Large B-cell Lymphoma at relapse. The re-biopsy is particularly recommended if relapse is over 1 year from previous complete remission. If this is harmful for the patient, the patient can be enrolled if archival tumor sample and block from first diagnosis are available.
• Measurable and/or evaluable disease
• Any Ann Arbor stage and IPI group at relapse
• Performance status \< 2 according to Eastern Cooperative Oncology Group (ECOG) scale unless due to lymphoma
• No Central Nervous System (CNS) disease (meningeal and/or brain involvement by lymphoma)
• Adequate haematological counts: Absolute Neutrophil Count (ANC) \> 1.5 x 109/L, Hgb \> 10.5 g/dl (transfusion independent), Platelet count \> 75 x 109/L (transfusion independent), with the exception of cytopenia due to lymphoma bone marrow involvement
• Normal liver function (ALP, AST, ALT, GGT, conjugated bilirubin total \< 2 x ULN) if not related to lymphoma
• Normal kidney function (creatinine clearance \>= 80 ml/min)
• Cardiac ejection fraction \> 50% (MUGA scan or echocardiography)
• Normal lung function
• Absence of active infections
• Non peripheral neuropathy or active neurological non neoplastic disease of CNS
• Non major surgical intervention prior 3 months to randomization if not due to lymphoma and/or not other disease life-threatening that can compromise chemotherapy treatment

You may not qualify if:

• Diagnosis of Lymphoblastic Lymphoma, Burkitt Lymphoma, Non Hodgkin Lymphoma CD20 negative, Mantle Cell Lymphoma, Follicular Lymphoma, Primary Mediastinal Lymphoma
• Age ≥ 65 years
• Patients ineligible to high-dose chemotherapy
• Performance status \> 2 according to ECOG scale if not due to lymphoma
• Patients who previously received GA101 (obinutuzumab) are excluded.
• Patient has known or suspected hypersensitivity or intolerance to Rituximab
• Patient has received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in nontreatment studies is allowed, if it will not interfere with participation in this study.
• CNS disease (meningeal and/or brain involvement by lymphoma)
• History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
• Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology). Patients with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing.
• Positive test results for hepatitis C (HCV antibody serology testing). Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
• Known history of HIV seropositive status. For patients with unknown HIV status, HIV testing will be performed at screening if required by local regulations.
• Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug
• Uncontrolled or severe cardiovascular disease including myocardial infarction within six months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
• Cardiac ejection fraction \< 45% (MUGA scan or echocardiography)

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (10)

Ospedale San Bortolo

Vicenza, VI, 36100, Italy

Location

Ospedale di Bolzano, Reparto di Ematologia & CTMO

Bolzano, 39100, Italy

Location

A.O. Universitaria Careggi

Florence, 50139, Italy

Location

Ospedale dell'Angelo, U.O. Ematologia

Mestre, 30174, Italy

Location

A.O. Universitaria Policlinico Di Modena

Modena, 41124, Italy

Location

Ematologia Policlinico San Matteo

Pavia, 27100, Italy

Location

AO di Perugia S. Maria della misericordia

Perugia, 06132, Italy

Location

Ematologia Ospedale S.Camillo Forlanini

Roma, 00149, Italy

Location

Policlinico Umberto I - Università "La Sapienza"

Roma, 00161, Italy

Location

Ematologia e Trapianto Istituto Regina Elena IFO

Roma, Italy

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

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

• Maurizio Martelli, MD

  Dipartimento di Biotecnologie Cellulari ed Ematologia, "La Sapienza" Roma

  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: February 17, 2015
• First Posted: February 27, 2015
• Study Start: November 5, 2014
• Primary Completion: February 1, 2018
• Study Completion: June 23, 2020
• Last Updated: June 6, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (10)