Daratumumab Plus Gemcitabine, Dexamethasone, Cisplatin in pt R/R CD38+ PTCL-NOS, AITL and TFH
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|ClinicalTrials.gov Identifier: NCT04251065|
Recruitment Status : Active, not recruiting
First Posted : January 31, 2020
Last Update Posted : March 3, 2022
|Condition or disease||Intervention/treatment||Phase|
|Refractory T-Cell Lymphoma Relapsed T-Cell Lymphoma||Drug: Daratumumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Intervention 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)|
|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|
|Actual Study Start Date :||September 3, 2020|
|Actual Primary Completion Date :||December 22, 2021|
|Estimated Study Completion Date :||December 1, 2024|
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.
Daratumumab in combination with Gemcitabine, Dexamethasone and Cisplatin (D-GDP).
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)
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.
Other Name: Darzalex
- Complete Response Rate (CRR) [ 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). ]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.
- Overall Response Rate (ORR) [ 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 ]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) [ 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). ]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) [ 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). ]
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 [ Time Frame: the endpoint will be assessed from the date of starting therapy to the end of the study (up to 42 months) ]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.
- Role of daratumumab maintenance [ Time Frame: The endpoint will be assessed at each restaging through study completion, up to 42 months. ]Comparison between the Complete Remission Rate (CRR), percentage of patient in complete remission, before and after maintenance therapy
- Role of daratumumab maintenance_CR vs PR [ Time Frame: The endpoint will be assessed at each restaging through study completion, up to 42 months. ]
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.
- Percentage of CD38 expression in correlation with the response to the treatment [ 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. ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04251065
|IRCCS Istituto Tumori Giovanni Paolo II - U.O.C Ematologia|
|Bari, Italy, 70124|
|Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia|
|Meldola, Italy, Forlì-Cesena|
|ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia|
|Milano, Italy, 20162|
|A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia|
|Palermo, Italy, 90146|
|Ospedale Guglielmo da Saliceto - U.O.Ematologia|
|Piacenza, Italy, 29121|
|A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria|
|Torino, Italy, 10126|
|Trieste - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia|
|Trieste, Italy, 34121 Francesco|
|Principal Investigator:||Francesco Zaja||S.C. Ematologia, Trieste - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia|