A Study to Evaluate the Safety and Pharmacokinetics of a Modified Tafasitamab IV Dosing Regimen Combined with Lenalidomide in Patients with Worsening (relapsed) or Unresponsive (refractory) Diffuse Large B-Cell Lymphoma (R/R DLBCL) (MINDway)
- Conditions
- Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)MedDRA version: 21.0Level: PTClassification code: 10012818Term: Diffuse large B-cell lymphoma Class: 100000004864Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-507993-42-00
- Lead Sponsor
- MorphoSys AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 51
1. Capable of giving signed informed consent as described in Appendix 2: Regulatory, Ethical, and Trial Oversight Considerations, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. Patient must be at least 18 years of age and of legal age (whichever is higher) in the jurisdiction in which the study is taking place at the time of signing the informed consent. 3. One of the following histologically confirmed diagnoses: • 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 • 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 follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia) into DLBCL with a subsequent DLBCL relapse are also eligible. 4. Tumor tissue for retrospective central pathology review must be provided as an adjunct to participation in this study. If archival formalin fixed paraffin embedded tumor tissue acquired =3 years prior to screening is not available, a fresh tumor tissue sample from the patient should be obtained. Archival formalin fixed- paraffin embedded tumor tissue acquired >3 years prior to screening is acceptable only in cases where a fresh tumor biopsy cannot be collected due to a safety risk, e.g., due to co-morbidity, or inaccessible tumor site., 5. Patients must have:a. Relapsed and/or refractory disease as defined in Appendix 3: Study Specific Definitions b. At least one bi-dimensionally measurable disease site. The lesion must have a greatest transverse diameter of = 1.5 cm and greatest perpendicular diameter of = 1.0 cm at baseline. The lesion must be positive on positron emission tomography (PET) scan (for definition see Juweid et al., 2007)c.Received at least one, but no more than three previous systemic regimens for the treatment of DLBCL and one therapy line must have included a cluster of differentiation-20 (CD20) targeted therapy (e.g., rituximab [RTX])d. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 6. Patients that are not eligible to undergo intensive salvage therapy including autologous stem cell transplantation (ASCT). The reason for a patient’s ineligibility must meet one of the criteria described below and documented in the patient’s source data:a. Inadequate performance status (Karnofsky performance status = 80%; seeAppendix 5: Karnofsky Performance Status Scale) b. Disease not responsive to salvage chemotherapy. Responsiveness is defined as a tumor demonstrating either complete response (CR) or partial response (PR) to salvage chemotherapy c. Inadequate major organ function (any of the below): i. symptomatic congestive heart failure ii. lung function-forced vital capacity (FVC), forced expiratory volume in 1 second (FEV-1), and corrected diffusion capacity of the lung for carbon monoxide (DLCO) = 60% iii. liver function-total serum bilirubin and transaminases > 2 x upper limit of normal (ULN) d. History or evidence of significant co-morbid medical or psychiat
1. General provisions: a. Patients who are legally institutionalized, or patients under judicial protection b. Concurrent enrollment in another interventional clinical study 2. Patients who have: a. Any other histological type of lymphoma including primary mediastinal (thymic) large B-cell (PMBL) or Burkitt lymphoma b. Known double/triple hit” genetics (high grade B-cell lymphoma) characterized by simultaneous detection of MYC with BCL2 and/or BCL6 translocation(s) defined by fluorescence in situ hybridization. MYC, BCL2, BCL6 testing prior to study enrollment is not required 3. Patients who have: a. Not discontinued (within 14 days prior to Day 1 dosing): CD20 targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma-specific therapy b. Undergone major surgery (within 4 weeks prior to Day 1 dosing) or suffered from significant traumatic injury c. Received live vaccines (within 4 weeks prior to Day 1 dosing) (See Appendix 7: Covid-19: Infection Prophylaxis and Vaccines) d. Required parenteral antimicrobial therapy for active, intercurrent infections (within 14 days prior to Day 1 dosing) 4. Patients who: a.Have, in the opinion of the investigator, not recovered sufficiently from the adverse toxic effects of prior therapies b. Were previously treated with tafasitamab or IMiDs® (e.g., thalidomide, LEN) c.Have a history of hypersensitivity to compounds of similar biological or chemical composition to tafasitamab, IMiDs® and/or the excipients contained in the study treatment formulations d. Have undergone ASCT within the period = 3 months prior to signing the ICF. Patients who have a more distant history of ASCT must exhibit full hematological recovery before enrollment into the study e. Have undergone previous allogenic stem cell transplantation f.Have a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or are at high risk for a thromboembolic event in the opinion of the investigator and who are not willing/able to take venous thromboembolism (VTE) prophylaxis during the entire treatment period g. Concurrently use other anticancer or experimental treatments, 5. History of other malignancy that could affect compliance with the protocol or interpretation of results. Exceptions:a.Patients with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for > 2 years prior to enrollment are eligible b. Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible 6. Patients with: a. Positive hepatitis B and/or C serology (see Appendix 8: Hepatitis Virus Serology for details) b. Known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV) c.Central nervous system (CNS) lymphoma involvement – present or past medical history d. History or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator’s opinion preclude participation in the study or compromise the patient’s ability to give informed consent e. History or evidence of rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption f.Gastrointestinal (GI) abnormalities (issue with absorption) inc
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To evaluate the safety and tolerability of tafasitamab administered once every 2 weeks (Q2W)/once every 4 weeks (Q4W) in combination with lenalidomide in R/R DLBCL patients<br>• To determine a recommended dose for tafasitamab Q2W/Q4W administration in combination with lenalidomide in R/R DLBCL patients;Secondary Objective: • To evaluate the pharmacokinetic profile of tafasitamab after Q2W/Q4W dosing in combination with lenalidomide • To assess anti-tumor activity of tafasitamab after Q2W/Q4W dosing in combination with lenalidomide • To assess the incidence of anti-drug antibodies to tafasitamab;Primary end point(s): Incidence and severity of TEAEs (TEAE, treatment-emergent adverse event)
- Secondary Outcome Measures
Name Time Method Secondary end point(s):• Tafasitamab serum concentrations after 3 (Ctrough and Cmax) and 12 (Ctrough) treatment cycles;Secondary end point(s):• Best Objective Response Rate (ORR) by Investigator assessment up to treatment Cycle 12 based on Cheson et al. (2007);Secondary end point(s):• Duration of Response (DoR) by Investigator assessment based on Cheson et al. (2007);Secondary end point(s):• Progression-Free Survival (PFS) by Investigator assessment based on Cheson et al. (2007);Secondary end point(s):• Number and percentage of patients developing anti- tafasitamab antibodies up to treatment Cycle 12