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

Primary Purpose

Refractory T-Cell Lymphoma, Relapsed T-Cell Lymphoma

Status
Active
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Daratumumab
Sponsored by
Fondazione Italiana Linfomi - ETS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory T-Cell Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

• 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
  • Subject must be able to adhere to the study visit schedule and other protocol requirements
  • Life expectancy ≥ 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, ovulation, symptothermal, post ovulation methods for the female partner] and withdrawal are not acceptable methods of contraception)

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 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)
  • 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

Sites / Locations

  • IRCCS Istituto Tumori Giovanni Paolo II - U.O.C Ematologia
  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia
  • ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia
  • A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia
  • Ospedale Guglielmo da Saliceto - U.O.Ematologia
  • A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria
  • Trieste - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Daratumumab-GDP

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall Response Rate (ORR)
Overall Response Rate is defined as the percentage of patients in complete remission or in partial remission (according to the Lugano 2014 criteria) after the first 4 cycles of therapy (cycles of 21 days). Patients without response assessment (due to whatever reason) will be considered as non-responders.
Overall Survival (OS)
Overall Survival, the percentage of patients alive, is defined from the start date of therapy to the date of death from any cause. 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)
The length of time during and after the treatment that patients live with the disease, but it does not get worse. 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. Responding patients, according to the Lugano classification response Criteria, and patients who are lost to follow-up will be censored at their last assessment date.
Toxicity - Incidence of relevant toxicities
Incidence of relevant toxicities. Toxicities will be classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. This endpoint will be evaluated from the start date of therapy and at any time during therapy and follow-up.

Full Information

First Posted
January 10, 2020
Last Updated
August 1, 2022
Sponsor
Fondazione Italiana Linfomi - ETS
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1. Study Identification

Unique Protocol Identification Number
NCT04251065
Brief Title
Daratumumab Plus Gemcitabine, Dexamethasone, Cisplatin in pt R/R CD38+ PTCL-NOS, AITL and TFH
Official Title
A Phase II, Open Label, Multicenter Trial of Daratumumab in Combination With Gemcitabine, Dexamethasone and Cisplatin (D-GDP) in Patients With 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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 3, 2020 (Actual)
Primary Completion Date
December 22, 2021 (Actual)
Study Completion Date
November 15, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione Italiana Linfomi - ETS

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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 Peripheral T-Cell Lymphoma Not Otherwise Specified (PTCL-NOS), Angioimmunoblastic T-cell lymphoma (AITL) or Nodal Lymphoma of T Follicular Helper cells (TFH cells) origin and a central evaluation of immunohistochemical positivity of CD38 (cluster of differentiation 38) 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. Induction phase: 4-6 courses (according to response after cycle 4 and to patient compliance) of D-GDP (Daratumumab in combination with Gemcitabine, Cisplatin, Dexamethasone) 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 Granulocyte-colony stimulating factor (G-CSF) from day 3 to 6, and from day 10 to 13 (to be prolonged if necessary) After 4 courses of D-GDP (Daratumumab in combination with Gemcitabine, Cisplatin, Dexamethasone), patients in Complete Remission/Partial Remission (CR/PR) and eligible for allogeneic stem cell transplantation (allo-SCT) will be addressed to allo-SCT consolidation. Otherwise, patients in Complete Remission (CR) will enter the maintenance phase at this point of the study. Patients in Partial Remission (PR) (not eligible for allogeneic stem cell transplantation) or in Stable Disease (SD) after D-GDP x 4 cycles can receive 2 additional courses of D-GDP before maintenance or can move directly to maintenance, according to center choice (based on patient condition, performance status and quality of response). Patients who respond (Complete Remission/Partial Remission) after 6 courses of induction phase (end of induction, EOI) and eligible to allogeneic stem cell transplantation (allo-SCT) will be addressed to allo-SCT consolidation. Patients who respond to the induction phase (Complete Remission/Partial Remission) and are not eligible for allogeneic stem cell transplantation (allo-SCT) and patients in stable disease (SD) at the End Of Induction (EOI), will move to the maintenance phase. Patients in Progressive disease (PD) at any time will discontinue treatment, as well as patients experiencing at any time unacceptable toxicity. Maintenance phase: 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 (Daratumumab in combination with Gemcitabine, Cisplatin, Dexamethasone) according to the following schedule: • Daratumumab 16 mg/kg single administration every 28 days Treatment with D-GDP (Daratumumab in combination with Gemcitabine, Cisplatin, Dexamethasone) or daratumumab single agent will be discontinued before completion of 24 cycles in case of: decision of the investigator to consolidate D-GDP (Daratumumab in combination with Gemcitabine, Cisplatin, Dexamethasone) response with allogeneic stem cell transplant disease progression unacceptable toxicity withdrawal of consent investigator determines that further therapy is not in the patient's best interest (e.g., due to non-compliance, toxicity, etc.) Adverse events ("Common Terminology Criteria for Adverse Events", CTCAE v. 5.0) will be monitored from the first study-related procedure, throughout treatment, maintenance and for 30 days after the end of treatment with the study drug. Safety monitoring and stopping rules: In order to monitor the safety and the activity of the treatment in small cohorts of patients, the Bayesian approach of Thall et al. (1995), as extended by Thall and Sung (1998) will be used. Monitoring of relevant toxicity after 4 cycles of D-GDP (Daratumumab in combination with Gemcitabine, Cisplatin, Dexamethasone) will be done to ensure that it is not higher than an acceptable toxicity of 30% (as defined in the safety endpoints) and the monitoring of activity after 4 cycles of D-GDP (Daratumumab in combination with Gemcitabine, Cisplatin, Dexamethasone) will be done to ensure that Complete Remission (CR) proportion is not lower than 40%. The prior probability of toxicity and activity are modeled by beta distributions [Beta (0.6,1.4) and Beta (0.8,1.2), respectively]. The enrolment will be stopped if the posterior probability of the treatment being more toxic or less active than expected is greater than 95%. The primary efficacy analysis will be performed after enrolment of 35 patients. The primary efficacy analysis will consist of an estimate of Complete Remission Rate (CRR) on the efficacy population after 4 cycles of D-GDP (Daratumumab in combination with Gemcitabine, Cisplatin, Dexamethasone) therapy, with 90% confidence intervals (according to 1-sided alpha error of 0.05). To conclude that the new treatment is promising, the minimum number of patients with a Complete Remission (CR) is 12/35. The time-to-event functions (Overall Survival (OS) and Progression Free Survival (PFS)) will be estimated by the Kaplan-Meier product-limit method. Subgroup analyses on primary efficacy parameter (Complete Remission Rate (CRR)) will be performed to assess the role of daratumumab maintenance and to explore potential prognostic role of CD38 expression. A logistic regression model will be used and the effect (Complete Remission Rate (CRR)) and its 95% Interval of Confidence (CI) will be presented. For safety analysis, both at patient level and at therapy cycle level, summaries of incidence rates (frequencies and percentages) and intensity of individual adverse events by CTCAE (Common Terminology Criteria for Adverse Events (CTCAE)) v. 5.0 will be reported. The results of this study will support the rationale of a phase III randomized trial if both efficacy and safety endpoints will be considered promising.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Daratumumab-GDP
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Other Intervention Name(s)
Darzalex
Intervention Description
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.
Primary Outcome Measure Information:
Title
Complete Response Rate (CRR)
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Overall Response Rate is defined as the percentage of patients in complete remission or in partial remission (according to the Lugano 2014 criteria) after the first 4 cycles of therapy (cycles of 21 days). Patients without response assessment (due to whatever reason) will be considered as non-responders.
Time Frame
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
Title
Overall Survival (OS)
Description
Overall Survival, the percentage of patients alive, is defined from the start date of therapy to the date of death from any cause. 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.
Time Frame
The end point will be assessed from the start date of therapy up to 24 months, and from the start date of therapy to the end of the study (up to 42 months).
Title
Progression-Free Survival (PFS)
Description
The length of time during and after the treatment that patients live with the disease, but it does not get worse. 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. Responding patients, according to the Lugano classification response Criteria, and patients who are lost to follow-up will be censored at their last assessment date.
Time Frame
The endpoint will be assessed from the start date of therapy up to 24 months and at the end of the study (up to 42 months).
Title
Toxicity - Incidence of relevant toxicities
Description
Incidence of relevant toxicities. Toxicities will be classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. This endpoint will be evaluated from the start date of therapy and at any time during therapy and follow-up.
Time Frame
the endpoint will be assessed from the date of starting therapy to the end of the study (up to 42 months)
Other Pre-specified Outcome Measures:
Title
Role of daratumumab maintenance
Description
Comparison between the Complete Remission Rate (CRR), percentage of patient in complete remission, before and after maintenance therapy
Time Frame
The endpoint will be assessed at each restaging through study completion, up to 42 months.
Title
Role of daratumumab maintenance_CR vs PR
Description
The evaluation of the rate of conversion in Complete Remission with daratumumab maintenance therapy for patients in Partial Remission after the induction. With this endpoint it will be measured the number of responses that will be converted from Partial Remission (PR) to Complete Remission (CR) in those patients that after induction therapy continued the treatment with the maintenance therapy.
Time Frame
The endpoint will be assessed at each restaging through study completion, up to 42 months.
Title
Percentage of CD38 expression in correlation with the response to the treatment
Description
This endpoint will evaluate the correlation between intensity of CD38 expression (percentage of expression) and response to the treatment. The extent of CD38 expression evaluated by the central designed laboratory of FIL (Fondazione Italiana Linfomi) will be performed on fresh sections cut from the paraffin block (or on unstained sections), and the percentage of positive tumor cells will be scored according to Bossard C. et al as follows: 4: >75%; 3: 50-75%; 2: 25-49%; 1: 5-24%; 0: <5%. The percentage of CD38 expression will be correlated with response measured according to the Lugano 2014 criteria
Time Frame
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 42 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: • 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 Subject must be able to adhere to the study visit schedule and other protocol requirements Life expectancy ≥ 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, ovulation, symptothermal, post ovulation methods for the female partner] and withdrawal are not acceptable methods of contraception) 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 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) 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesco Zaja
Organizational Affiliation
S.C. Ematologia, Trieste - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia
Official's Role
Principal Investigator
Facility Information:
Facility Name
IRCCS Istituto Tumori Giovanni Paolo II - U.O.C Ematologia
City
Bari
ZIP/Postal Code
70124
Country
Italy
Facility Name
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia
City
Meldola
ZIP/Postal Code
Forlì-Cesena
Country
Italy
Facility Name
ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia
City
Palermo
ZIP/Postal Code
90146
Country
Italy
Facility Name
Ospedale Guglielmo da Saliceto - U.O.Ematologia
City
Piacenza
ZIP/Postal Code
29121
Country
Italy
Facility Name
A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Trieste - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia
City
Trieste
ZIP/Postal Code
34121 Francesco
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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