MOR208C310
Not applicable (retrospective, observational study)
Abgeschlossen
Herr Dr. Stephan Parche
stephan.parche@morphosys.com
MorphoSys AG (Unternehmen, 11899)
Semmelweisstr. 7
82152 Planegg
To compare the efficacy outcomes of the L-MIND cohort with the effectiveness in a matched patient population treated with systemic NCCN/ESMO guideline listed regimens administered in routine clinical care
1. To compare the effectiveness of each pre-specified matched treatment cohort, i.e., BR, R-GemOx, R2, CD19 CAR-T, Pola-BR or Pixantrone monotherapy with the efficacy outcomes of the L-MIND cohort
2. To characterize the effectiveness of systemically administered therapies for R/R DLBCL therapy
3. To characterize the tolerability of systemically administered therapies in comparison with the L-MIND cohort by time on therapy and reason for discontinuation
The retrospective observational cohort consists of patients who have received at least 2 systemic regimens for the treatment of DLBCL at time of enrolment.
Sample size:
- Data to be collected from approximately 2000 patients for interim cohort balancing.
- Data to be collected from an estimated additional 800 patients. The number may change if actual data is available and necessitates adaptation.
Propensity score (PS) methodology will be employed to balance L-MIND and observational cohorts. The following baseline covariates will be considered: age, number of prior therapy lines, refractoriness status to the last prior therapy, elevated lactate dehydrogenase (LDH) levels, Ann Arbor stage, history of primary refractoriness, prior ASCT, neutropenia, anemia.
Patients who fulfilled eligibility criteria will qualify for matching if they have a sufficient follow-up for a documented response or progression to the respective treatment regimen and data on all baseline covariates are available at the start of the respective treatment.
Primary objective: To compare the efficacy outcomes of the L-MIND cohort with the effectiveness in a matched patient population treated with systemic regimens used in real-world.
To achieve this, subgroup strata will be categorized on the basis of number of lines of therapy, i.e., two or three or four therapy lines. 1:N nearest neighbour matching without replacement will be performed using the remaining eight baseline covariates per each strata to get each matched population set. The final matched population for analysis is the aggregation of the matched population of each strata.
Additional matched cohorts will be created on the basis of the following two subgroups of the L-MIND cohort:
- one prior line before LEN/tafasitamab
- two/three prior lines before LEN/tafasitamab
“1:N” denotes the ratio of L-MIND cohort to the observational cohort with a maximum ratio of 1:4. In the interim cohort balancing, prior to the data base lock, nearest neigbour matching will be performed stepwise increasing the matching ratio from 1:1 to 1:4 until for one or more baseline covariates a standardized mean difference (SMD) of 0.2 is exceeded.
The matched population with SMD d0.2 for all baseline characteristics and the highest matching ratio will be selected as the main analysis set for endpoint calculations.
Secondary objective 1: To compare the efficacy outcomes of each pre-specified matched treatment regimen with the L-MIND cohort.
To achieve this, 1:N nearest neighbour matching for nine baseline characteristics will be employed as described for the primary objective.
Data from patients who received pre-specified treatment regimens in different lines of therapy can be utilized in matched population sets under different treatment regimens.
Effectiveness endpoints:
OS serves as the primary endpoint, whereas ORR, CR, DoR, PFS, EFS, and TTNT serve as secondary endpoints. All time to event endpoints will be analysed using standard Kaplan-Meier methodology, log-rank test and hazard ratio will be estimated based on Cox proportional hazard model. ORR and CR will be compared between the cohorts using Fisher exact test, and Odds ratio estimated using logistic regression model.
For secondary objectives 2 and 3 descriptive statistics will be presented on various population sets, no hypothethesis testing will be performed.
Overall Survival (OS)
• Overall/Objective Response Rate (ORR)
• Complete Response Rate (CR)
• Duration of Response (DoR)
• Event Free Survival (EFS)
• Progression Free Survival (PFS)
• Time to next treatment (TTNT)
• Treatment discontinuation rate due to adverse events
• Duration of treatment exposure
1. Age e 18 years at the initial DLBCL diagnosis.
2. One of the following histologically confirmed diagnosis: DLBCL not otherwise specified (NOS); T-cell/histiocyte rich large B-cell lymphoma (THRLBCL); Epstein-Barr virus (EBV) positive DLBCL of the elderly (EBV-positive DLBCL), Grade 3b Follicular Lymphoma (FL), Composite lymphoma with a DLBCL component with a subsequent DLBCL relapse, according to the Revised European American Lymphoma/World Health Organization (REAL/WHO) classification. Additionally, patients with the evidence of histological transformation to DLBCL from an earlier diagnosis of low grade lymphoma (i.e., an indolent pathology such as FL, marginal zone lymphoma, chronic lymphocytic leukemia) into DLBCL with a subsequent DLBCL relapse are also eligible.
3. Relapsed or refractory DLBCL and received at least 2 systemic regimens for the treatment of DLBCL, including at least 1 anti-CD20 containing therapy.
1. Patients with central nervous system (CNS) involvement by lymphoma at initial DLBCL diagnosis.
2. Patients who were treated with CD19-targeted therapy or immunomodulatory drugs (IMiDs) (e.g., thalidomide, LEN) as a frontline DLBCL therapy.
3. Patients who underwent an allogeneic stem cell transplant.
4. Patients who had a prior history of malignancies other than DLBCL, unless the patient has been free of the disease for e5 years prior to inclusion.
Note: Patients with the following malignancies within the 5 years period are still eligible:
a. basal cell carcinoma of the skin
b. squamous cell carcinoma of the skin
c. carcinoma in situ of the cervix
d. carcinoma in situ of the breast
e. carcinoma in situ of the bladder
f. incidental histological finding of prostate cancer (Tumor/Node/Metastasis [TNM] stage of T1a or T1b)
5. Patients who received Tafasitamab.
Start of data collection: 01 Apr 2020 (actual)
End of data collection: 17 July 2020 (planned)
Globally: approximately 280 sites
Germany: approximately 40 sites
MorphoSys AG
Semmelweisstr. 7
82152 Planegg
Germany
Investigator fees: up to 930 EUR per patient entered into the eCRF (depending on the number of lines being entered)
Nein
