E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia |
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E.1.1.1 | Medical condition in easily understood language |
Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009310 |
E.1.2 | Term | CLL |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10076596 |
E.1.2 | Term | Marginal zone lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012883 |
E.1.2 | Term | Diffuse lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080213 |
E.1.2 | Term | In situ follicular lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10026801 |
E.1.2 | Term | Mantle cell lymphoma refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10026800 |
E.1.2 | Term | Mantle cell lymphoma recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
* Dose confirmation period (Phase 1b): To determine the safety, tolerability, and DLTs of combination therapy with tafasitamab + parsaclisib in participants with R/R NHL or CLL who have been previously treated with at least 2 prior lines of systemic anti-lymphoma therapy.
* Dose expansion period (Phase 2a): To assess the preliminary efficacy of combination therapy with tafasitamab + parsaclisib in participants with R/R NHL or CLL who have been previously treated with at least 2 prior lines of systemic anti-lymphoma therapy. |
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E.2.2 | Secondary objectives of the trial |
To estimate the PK of tafasitamab when given as combination therapy with parsaclisib |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* Men and women aged ≥ 18 years at the time of consent.
* Ability to comprehend and willingness to sign a written ICF and comply with all study visits and procedures.
* Histologically confirmed R/R B-cell malignancy of the following types: a. Cohort 1: DLBCL not otherwise specified, T-cell/histiocyte-rich large B-cell lymphoma, Epstein-Barr virus–positive DLBCL of the elderly, Grade 3b FL, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma), histological transformation from an earlier diagnosis of low-grade lymphoma (such as FL, MZL, CLL) into DLBCL b. Cohort 2: MCL with documentation of either overexpression of cyclin D1 or t(11;14) c. Cohort 3: FL Grade 1, 2, and 3a d. Cohort 4: MZL, including extranodal, nodal, and splenic subtypes e. Cohort 5: CLL or SLL
* Received at least 2 prior systemic treatment regimens as follows: a. Cohorts 1 and 2 (DLBCL, MCL): Must have been previously treated with at least 1 prior chemoimmunotherapy regimen that included an anti-CD20 antibody. This includes treatments such as chemotherapy plus rituximab or obinutuzumab, with or without rituximab or obinutuzumab maintenance. Note: At least 6 doses of anti-CD20 chemoimmunotherapy must have been given in prior therapy. b. Cohorts 3 and 4 (FL, MZL): Must have been previously treated with at least 1 prior chemoimmunotherapy or immunotherapy regimen that included an anti-CD20 antibody. This includes treatments such as rituximab or obinutuzumab monotherapy or chemotherapy plus rituximab or obinutuzumab, with or without rituximab or obinutuzumab maintenance. Note: At least 6 doses of anti-CD20 immunotherapy must have been given in prior therapy. c. Cohort 5 (CLL/SLL): Must have been previously treated with at least 1 prior systemic therapy including a BTK inhibitor regimen or chemoimmunotherapy regimen that included an anti-CD20 antibody.
* Relapsed, progressive, or refractory NHL or CLL: a. Relapsed: PD after response of CR to prior therapy. b. Progressive: PD after response of PR or stable disease to prior therapy. c. Refractory: achieved less than PR to the last prior therapy, or achieved a CR or PR that lasted < 6 months before PD. |
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E.4 | Principal exclusion criteria |
* Any other histological type of lymphoma according to the WHO 2016 classification of lymphoid neoplasms, for example, primary mediastinal B-cell lymphoma, Burkitt lymphoma, B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma (gray zone lymphoma); primary effusion lymphoma; primary cutaneous DLBCL, leg type; intravascular B cell lymphoma.
* History of or evidence of CNS lymphoma (primary and secondary).
* Any anticancer and/or investigational therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, or tumor embolization) within 30 days or 5 half-lives (whichever is greater) prior to the first dose of study treatment (C1D1).
* Inadequate recovery (> Grade 1) from toxicity and/or complications from a major surgery before C1D1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
* Dose confirmation period (Phase 1b): Incidence and severity of TEAEs and incidence of DLTs.
* Dose expansion period (Phase 2a): ORR, defined as the percentage of participants having best response of CR/CMR or PR/PMR per investigator assessment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
* Dose confirmation period (Phase 1b): after 1 cycle (28 days)
* Dose expansion period (Phase 2a): ORR will be analyzed when all subjects in the respective cohort have received at least 1 post-baseline disease assessment or have progressed, withdrawn from the study, or died |
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E.5.2 | Secondary end point(s) |
PK parameters of tafasitamab when given in combination with parsaclisib. Ctrough (ie, predose), Cmax, tmax, Cmin, and AUCt will be summarized by descriptive statistics. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
France |
Germany |
Italy |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |