Relapsed/refractory CD38 positive peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and other nodal lymphomas of TFH cell origin MedDRA version: 20.0 Level: PT Classification code 10042971 Term: T-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
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Product Name: Darzalex
Product Code: [IMP1]
Pharmaceutical Form: Conce
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically documented diagnosis of CD38 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 18-75 years •Relapsed or refractory to at least one and a maximum of two previous lines of treatment •Eastern Cooperative Oncology Group (ECOG) performance status (PS)= 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 10^9/L unless due to bone marrow involvement by lymphoma - Platelet count = 50.000/mm^3 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 months •Women must be: - postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months) - surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), - completely abstinent (periodic abstinence from intercourse is not permitted) or if sexually active, be practicing two highly effective methods of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double barrier method (e.g.: condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization) as local regulations permit, before entry, and must agree to continue to use the same method of contraception throughout the study. They must also be prepared to continue birth control measures for at least 3 months after terminating treatment. - Women of childbearing potential must have a negative pregnancy test at screening •Men must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study. Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug. •Male even if surgically sterilized (i.e., status post vasectomy) must agree to 1 of the following: - practice effective barrier contraception during the entire study treatment period and through 3 months after the last dose of study drug, or - agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovu
Exclusion criteria
Exclusion criteria: • 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 antiCD38 • Concomitant experimental therapy • Relapse after allo SCT • 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-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) • Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent • Any history of other active malignancies within 3 years prior to study entry, with the exception of adequately treated in situ carcinoma of the cervix uterine, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, previous malignancy confined and surgically resected with curative intent. • Uncontrolled and/or active systemic infection (viral, bacterial or fungal) • Evidence of any other clinically significant uncontrolled condition(s) • If female, the patient is pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of 4 courses of D-GDP in terms of complete response in patients with PTCL-NOS, AILT and other nodal lymphomas of TFH cell origin refractory/relapsed after at least one and no more than two previous lines of therapy.;Secondary Objective: -To evaluate the Overall Response Rate (ORR) (Lugano 2014); -To evaluate the efficacy in terms of Overall survival (OS); -To evaluate the efficacy in terms of Progression-free survival (PFS); -To evaluate the safety of D-GDP combination. Explorative objectives -To assess the role of daratumumab maintenance; -To evaluate the association between intensity of CD38 expression and response.;Primary end point(s): Complete Response Rate (CRR);Timepoint(s) of evaluation of this end point: Complete Response Rate (CRR) after first 4 cycles of D-GDP. CRR will be defined as the proportion of patient in CR according to Lugano classification response Criteria after the first 4 cycles of D-GDP. In case of early discontinuation, efficacy will be assessed at the EOT visit. Patients without response assessment (due to whatever reason) will be considered as non-responders. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: At each restaging Role of daratumumab maintenance by comparison of CRR (complete response rate) before and after maintenance, and by evaluation of rate of conversion in CR with daratumumab maintenance for patients in PR after the induction.; Overall Survival (OS) will be defined from the date of starting therapy and the date of death from any cause. The endpoint will be evaluated at 24 months and at the end of the study Patients alive and those who are lost to follow-up at the time of the final analysis will be censored at the date of the last contact.; Progression-Free Survival (PFS) will be defined from the date of starting therapy and the date of disease progression, relapse or death from any cause. The endpoint will be evaluated at 24 months and at the end of the study Responding pati;Secondary end point(s): Explorative efficacy endpoints: Role of daratumumab maintenance; OS (Overall Survival); PFS, Progression-Free Survival; Overall Response Rate ORR (=Complete remission, CR + Partial Response, PR); Relevant toxicity; Explorative efficacy endpoints: Association between intensity of CD38 expression and response | — |
Countries
Italy
Contacts
Public ContactArea Start up
FONDAZIONE ITALIANA LINFOMI ONLUS
Outcome results
None listed