Daratumumab Plus Gemcitabine, Dexamethasone, Cisplatin in pt R/R CD38+ PTCL-NOS, AITL and TFH

NCT04251065 | Terminated Phase 2 Results DMC

• 1 other identifier: FIL_Dara-GDP
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 7

Brief Summary

FIL\_Dara-GDP is a phase II, open label, multicenter clinical trial. The sponsor of this clinical trial is Fondazione Italiana Linfomi (FIL). The primary objective is to evaluate the efficacy of 4 courses of D-GDP (Daratumumab in combination with Gemcitabine, Cisplatin, Dexamethasone) in terms of complete response in patients with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and other nodal lymphomas of T follicular helper cells (TFH cells) origin refractory/relapsed after at least one and no more than two previous lines of therapy.

Conditions

Refractory T-Cell Lymphoma; Relapsed T-Cell Lymphoma

Keywords

CD38 positive; R/R peripheral T-cell lymphoma (PTCL-NOS); R/R angioimmunoblastic T-cell lymphoma (AITL); R/R nodal lymphomas of T follicular helper (TFH) cells; Daratumumab; Gemcitabine; Dexamethasone; Cisplatin

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CRR)

  The Complete Response Rate is defined as the percentage of patient in Complete Remission (according to Lugano classification response Criteria). It will be assessed after the first 4 cycles of D-GDP chemotherapy. In case of early discontinuation, efficacy will be assessed at the End Of Treatment (EOT) visit. Patients without response assessment (due to whatever reason) will be considered as non-responders. CR: complete radiological response, no extralymphatic sites, no new lesions, organ enlargement regress to normal and normal morphology of bone marrow; PR: \>=50% decrease of sum of the product of perpendicular diameter of up to 6 dominant, measurable nodes and and extranodal sites.

  the endpoint will be assessed from the start date of therapy to the end of the first four cycles of therapy (cycles of 21 days).

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  the endpoint will be assessed from the start date of therapy to the end of the first four cycles of therapy (cycles of 21 days) and at each restaging

• Overall Survival (OS)

  The end point will be assessed from the start date of therapy up to 3 months.

• Progression-Free Survival (PFS)

  The endpoint will be assessed from the start date of therapy up to 3 months.

• Toxicity - Frequency of Relevant Toxicities

  the endpoint was assessed after 26 months from the date of starting therapy in place of the planned 42 months, due the early interruption of the study

Other Outcomes (3)

• Role of Daratumumab Maintenance

  The endpoint will be assessed at each restaging through study completion, up to 26 months.

• Role of Daratumumab Maintenance CR vs PR

  The endpoint will be assessed at each restaging through study completion, up to 26 months.

• Percentage of CD38 Expression in Correlation With the Response to the Treatment

  The endpoint will be assessed from the start date of therapy to the end of the first four cycle of therapy (cycles of 21 days) and at each restaging through study completion, up to 26 months.

Study Arms (1)

Daratumumab-GDP

EXPERIMENTAL

This is an open-label, multicenter, single arm, single-stage phase II trial. After the patient signs the written informed consent the patient will enter the screening phase planning baseline assessments and a concomitant upfront confirmation of diagnosis of PTCL-NOS, AITL or nodal lymphoma of TFH cell origin and a central evaluation of immunohistochemical positivity of CD38 on bioptic material used to perform local diagnosis of relapsed disease, or that used for the more recent biopsy in the case of refractory patients. A core needle biopsy is considered sufficient for review and CD38 evaluation. Evaluation at central laboratory can be performed in bone marrow sections in those patients with only bone marrow lymphoma infiltration. Only patients with confirmed eligible diagnosis and a percentage of CD38 positive tumor cells ≥ 5% will be considered eligible for study treatment. The treatment consists of an induction phase and a maintenance phase.

Drug: Daratumumab

Interventions

Daratumumab DRUG

Daratumumab in combination with Gemcitabine, Dexamethasone and Cisplatin (D-GDP). Induction phase: 4-6 courses (according to response after cycle 4 and to patient compliance) of D-GDP every 21 days pursuant to the following schedule: Daratumumab cycle 1: 8 mg/kg i.v. on day 2 and on day 9; cycle 2-6: 16 mg/kg i.v. on day 2 and day 9) Gemcitabine 1000 mg/sm i.v. day 1 and day 8 (gemcitabine on day 8 to be skipped in case of grade 3-4 toxicity) Cisplatin 75 mg/sm i.v. day 1 Dexamethasone 40 mg i.v. or po days 1-2-3-4-9 G-CSF from day 3 to 6, and from day 10 to 13 (to be prolonged if necessary) Maintenance: starting 28 days after the beginning of cycle 4 or 6 (or, in case of toxicity grade \> 1, after toxicity is resolved) and up to 24 cycles from start of D-GDP according to the following schedule: Daratumumab 16 mg/kg single administration every 28 days.

Also known as: Darzalex

Daratumumab-GDP

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented diagnosis of CD38 (cluster of differentiation 38) positive PTCL-NOS, AITL and other nodal lymphomas of TFH cell origin as defined in the 2017 edition of the World Health Organization (WHO) classification. Patients with only bone marrow involvement are eligible.
• Note: Only patients with a centrally assessed percentage of CD38 positive tumor cells ≥ 5% in the relapse biopsy, or in the more recent biopsy in the case of refractory patients, will be considered eligible for protocol study treatment.
• Age 18-70 years
• Relapsed or refractory to one previous lines of treatment (autologous transplantation as a consolidation to the first line of therapy should not be considered a second line)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) \< 2
• At least one site of measurable nodal disease at baseline ≥ 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan cannot be performed). Note: Patients with only bone marrow involvement are eligible
• Adequate hematological counts defined as follows:
• Absolute Neutrophil count (ANC) \> 1.0 x 109/L unless due to bone marrow involvement by lymphoma
• Platelet count \> 100.000/mm3 unless due to bone marrow involvement by lymphoma
• Adequate renal function defined as follows:
• \- Creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula)
• Adequate hepatic function per local laboratory reference range as follows:
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN)
• Bilirubin ≤1.5 x upper limit of normal (ULN)(unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
• Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures

You may not qualify if:

• Histological diagnosis different from CD38 positive PTCL-NOS, AITL, and other nodal lymphomas of TFH cell origin
• More than two lines of previous treatment (autologous stem cell transplant performed as part of consolidation to a previous line of therapy should not be considered as a line of therapy)
• Previous treatment with Gemcitabine or Platinum based regimens; patients who received a single course of Platinum based course (i.e. DHAP) are not excluded
• Prior therapy with monoclonal antibody anti CD38 (against cluster of differentiation 38)
• Concomitant experimental therapy
• Relapse after allo SCT
• Central nervous system (CNS) involvement with lymphoma
• Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug
• Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment
• Subject is:
• Known to be seropositive for human immunodeficiency virus (HIV)
• Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-hepatitis B core antigen (HBc)\] ± antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
• Known to be seropositive for hepatitis C (except in the setting of a Sustained Virologic Response(SVR), defined as aviremia at least 12 weeks after completion of antiviral therapy)
• Cardiovascular disease (NYHA class ≥2)
• Creatinine Clearance \< 40 mL/min (Cockcroft-Gault formula)

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (7)

IRCCS Istituto Tumori Giovanni Paolo II - U.O.C Ematologia

Bari, 70124, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia

Meldola, Forlì-Cesena, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia

Milan, 20162, Italy

Location

A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia

Palermo, 90146, Italy

Location

Ospedale Guglielmo da Saliceto - U.O.Ematologia

Piacenza, 29121, Italy

Location

A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria

Torino, 10126, Italy

Location

Trieste - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia

Trieste, 34121 Francesco, Italy

Location

MeSH Terms

Conditions

Lymphoma, T-Cell

Interventions

daratumumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Due early termination, only 8 patients were enrolled in the study. The study highlight a high level of toxicity of the experimental treatment.

Results Point of Contact

• Title: Prof. Francesco Zaja
• Organization: SC Ematologia - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - Trieste

francesco.zaja@asugi.sanita.fvg.it

+ 39 040 3992015

Study Officials

• Francesco Zaja

  S.C. Ematologia, Trieste - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Model Details: Prospective, multicenter, single arm, single-stage phase II trial in patients with refractory/relapsed CD38 positive PTCL-NOS, AITL and TFH with centrally assessed CD38 expression ≥ 5%. It is expected for the current trial that D-GDP will improve the CR rate to 40% with an absolute improvement of 20%, while the toxicity rate is maintained at 30%. Sample size: A'Hern's Single-Stage Phase II design will be used. The sample size was calculated according to the primary efficacy endpoint. Based on literature, the null hypothesis that the true proportion of CR after four courses of D-GDP is 0.20 will be tested against an alternative CR proportion of 0.40 with an absolute improvement of 0.20, considered clinically promising with the experimental treatment. Assuming a type I error rate of 5% and a power of 80% when the CR proportion is 40% overall 35 patients will be accrued. The null hypothesis will be rejected if 12 or more CR out of 35 patients are observed after four courses of D-GDP.

Study Record Dates

• First Submitted: January 10, 2020
• First Posted: January 31, 2020
• Study Start: September 3, 2020
• Primary Completion: December 22, 2021
• Study Completion: November 23, 2022
• Last Updated: March 28, 2025
• Results First Posted: March 28, 2025

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (7)