Phase Ib Study to Assess Safety and Preliminary Efficacy of Tafasitamab or Tafasitamab Plus Lenalidomide in Addition to R-CHOP in Patients With Newly Diagnosed DLBCL

Phase 1

Completed

• Conditions: Diffuse Large B-cell Lymphoma
• Interventions: Drug: Tafasitamab plus lenalidomide; Drug: Tafasitamab

• Registration Number: NCT04134936
• Lead Sponsor: MorphoSys AG

Brief Summary

This is an open-label, randomized, multicentre study to evaluate safety and preliminary efficacy of the human anti-CD19 antibody Tafasitamab in addition to R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) or Tafasitamab and Lenalidomide in addition to R-CHOP in adult patients with newly diagnosed, previously untreated Diffuse Large B-cell Lymphoma (DLBCL).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-11
• Study First Submitted QC: 2019-10-21
• Study First Posted: 2019-10-22
• Study Start: 2019-12-11
• Primary Completion: 2021-02-11
• Study Completion: 2022-08-10
• Results First Submitted: 2023-09-12
• Status Verified: 2024-10
• Results First Submitted QC: 2024-10-11
• Last Update Submitted: 2024-10-11
• Results First Posted: 2024-10-16
• Last Update Posted: 2024-10-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

1. Age >18 years

2. Histologically confirmed diagnosis of DLBCL, not otherwise specified (NOS)

3. Tumor tissue for retrospective central pathology review and correlative studies must be provided.

4. At least one bidimensionally measurable, PET positive disease site (greatest transverse diameter of ≥1.5 cm, greatest perpendicular diameter of ≥1.0 cm)

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

6. International Prognostic Index (IPI) status of 2 to 5

7. Appropriate candidate for R-CHOP

8. Left ventricular ejection fraction (LVEF) of ≥50% assessed by echocardiography or cardiac multi-gated acquisition (MUGA) scan

9. Adequate hematologic, liver and renal function

10. Females of childbearing potential (FCBP) must:

    • not be pregnant
    • refrain from breast feeding and donating oocyte
    • agree to ongoing pregnancy testing
    • commit to continued abstinence from heterosexual intercourse, or agree to use and be able to comply with the use of double-barrier contraception

11. Males must:

    • use an effective barrier method of contraception if sexually active with FCBP
    • refrain from donating sperm

12. In the opinion of investigator, the patient must be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events

Major

Exclusion Criteria

1. Any other histological type of lymphoma according to World Health Organization (WHO) 2016 classification of lymphoid neoplasms, known double- or triple-hit lymphoma

2. Transformed non-Hodgkin lymphoma (NHL) and/or evidence of composite lymphoma

3. History of radiation therapy to ≥25% of the bone marrow or history of anthracycline therapy

4. History of prior non-hematologic malignancy except for the following:

   • Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening
   • Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer
   • Adequately treated carcinoma in situ without current evidence of disease

5. History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening arrhythmias

6. Patients with:

   • positive test results for active hepatitis B and C
   • known seropositive for or history of active viral infection with human immunodeficiency virus (HIV)
   • known active bacterial, viral, fungal, mycobacterial, or other infection at screening
   • known central nervous system (CNS) lymphoma involvement
   • history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator opinion preclude participation in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	Tafasitamab plus lenalidomide	Tafasitamab plus lenalidomide in addition to R-CHOP
Arm A	Tafasitamab	Tafasitamab in addition to R-CHOP

Primary Outcome Measures

Name	Time	Method
Incidence and Severity of Treatment-emergent Adverse Events (TEAEs)	6 months approximately

Secondary Outcome Measures

Name	Time	Method
Best Objective Response Rate (ORR) Until the End of Study (EOS)	24 months approximately	The best ORR was defined as the proportion of patients with Complete Response (CR) or Partial Response (PR) as the best response until the EOS.
Metabolic, PET-negative Complete Response (CR) Rate Until the End of Study	24 months approximately
Anti-tafasitamab Antibodies Formation	12 months approximately
Objective Response Rate (ORR) at the End of Treatment (EOT)	6 months approximately	The ORR at EOT was defined as the proportion of patients with Complete Response (CR) or Partial response (PR) based on the response achieved at the EOT Visit/early treatment discontinuation visit.
Metabolic, PET-negative Complete Response (CR) Rate at the End of Treatment	6 months approximately
Incidence and Severity of Adverse Events (AEs) in the Follow-up (FU) Period	18 months for non-treatment emergent adverse events, 6 months for treatment emergent adverse events
Progression-free Survival (PFS) at 12 and 24 Months	24 months approximately	As many patients had their data censored, due to completing the study without disease progression or death due to any cause, the probability of PFS (%) was used.
Event-free Survival (EFS) at 12 and 24 Months	24 months approximately	As many patients had their data censored, due to completing the study without disease progression, death due to any cause, or the start of a new anti-lymphoma treatment, the probability of EFS (%) was used.
Time to Next Anti-lymphoma Treatment (TTNT)	24 months approximately	As many patients had their data censored, due to completing the study without needing to receive another anti-lymphoma treatment, the Probability of TTNT (%) was used. Time to next anti-lymphoma treatment survival % estimate was the estimated probability that a patient remained TTNT-free up to the specified point in time.
Overall Survival at 12 and 24 Months	24 months approximately	As many patients had their data censored, due to completing the study without death from any cause, the probability of OS (%) was used.

Trial Locations

Locations (1)

MorphoSys Research Site; 🇪🇸 Vitoria-Gasteiz 1009, Spain