Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
183
Countries
1
Sites
1
Lymphoma
The primary objective is to evaluate the efficacy of R-Hyper-CVAD/R-MA
Key facts
- Sponsor
- Karolinska University Hospital
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Trial duration
- 8 Nov 2024 → ongoing
- Decision date (initial)
- 2024-03-08
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The primary objective is to evaluate the efficacy of R-Hyper-CVAD/R-MA
Secondary objectives 1
- The secondary objective is to evaluate the safety of R-Hyper-CVAD/R-MA
Conditions and MedDRA coding
Lymphoma
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Written informed consent according to ICH-GCP guidelines
- Age ≥ 18 and < 65 years
- Eligible to receive at least 4 courses of R-Hyper-CVAD/R-MA per investigator determination (a compound clinical judgement based on all available information, in which the clinical performance, comorbidity, biological age, the patient’s social situation and lymphoma status are considered.)
- Aggressive, untreated, de novo CD20+ aggressive B-cell lymphoma, including: Diffuse large B-cell lymphoma (NOS, GCB, non-GCB or ABC); Large B-cell lymphoma with 11q aberration; Primary diffuse large B-cell lymphoma of the testis; Primary cutaneous diffuse large B-cell lymphoma, leg type; Intravascular large B-cell lymphoma; HHV-8 and EBV-negative primary effusion-based lymphoma; EBV-positive diffuse large B-cell lymphoma, NOS; High-grade B-cell lymphoma, NOS; High-grade B-cell lymphoma with MYC and BCL2 rearrangements; High-grade B-cell lymphoma with MYC and BCL6 rearrangements; Primary mediastinal B-cell lymphoma; T cell/histiocyte-rich B-cell lymphoma; Follicular lymphoma grade 3B; Lymphomatoid granulomatosis grade 3; Mediastinal gray-zone lymphoma; Aggressive B-cell lymphoma, NOS or unclassifiable
- At least one of four, as per protocol defined, high-risk criteria must be fufilled
- Women of child-bearing potential, only after using a acceptable effective method of contraception (defined in the study protocol) during treatment and for six months after completion of treatment.
- Sexually active male participants must agree to use barrier prevention (condom) to ensure that embryos/fetuses are not exposed to study drugs via sperm, during treatment and for six months after completion of treatment; non-pregnant, fertile female partners to male participants are also recommended to use an acceptable method of birth control to avoid accidental pregnancy.
Exclusion criteria 14
- Pregnant or breast-feeding mother
- Psychiatric disorder or dementia which make the patient unable to give an informed consent and/or adhere to the schedule
- TdT-positive lymphoma
- CD34-positive lymphoma
- Previous organ transplantation
- Men and women of reproductive potential not agreeing to use an acceptable method of birth control (defined in study protocol) during treatment and for six months after completion of treatment
- Excluded diagnoses: CD20 negative lymphoma; Primary CNS lymphoma; Mantle cell lymphoma, including blastic/pleiomorphic types; Transformed lymphoma; Plasmablastic lymphoma; Lymphoblastic lymphoma; Post-transplant lymphoproliferative disorder; Burkitt leukaemia (≥25% Burkitt cells in bone marrow); Burkitt lymphoma
- Previous or concomitant diagnosis of another hematological malignancy
- Previous or concomitant diagnosis of another malignancy which is likely to cause death within 3 years
- Evidence of significant, uncontrolled concomitant disease(s) that could affect compliance with the protocol or interpretation of results
- Previous chemotherapy for any malignancy
- Estimated glomerular filtration rate <60 ml/min (unless due to lymphoma)
- Impaired liver function, defined as serum total bilirubin > 2 x ULN (> 3 x ULN if Gilbert’s syndrome) or serum ALT and AST ˃ 3 x ULN (unless due to lymphoma)
- Unstable angina pectoris, cardiac infarction within 3 months or congestive heart failure New York Heart Association Class II-IV (unless due to lymphoma)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 10
- Event-free survival (EFS) at 3 years
- EFS
- Progression-free survival (PFS)
- Overall survival (OS)
- Lymphoma-specific survival (LSS)
- Overall response rate (ORR)
- Complete response rate (CRR)
- Response rates after 6 cycles
- Response rates at final assessment in trial
- Response duration
Secondary endpoints 10
- Treatment-related mortality/Non-lymphoma mortality
- Time from diagnostic biopsy to start of chemotherapy and to start of steroids.
- Number and duration of scheduled and unscheduled hospital admissions
- Use of IV antibiotics
- Total number of hospital days
- Time between chemotherapy regimens and total time from starting to ending treatment within trial
- Reconstitution of T-cell (cellular and humoral) immunity
- Time on sick leave
- Long-term cardiac toxicity
- Second primary malignancies
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 11
Methotrexate Ebewe, 100 mg/ml, koncentrat till infusionsvätska, lösning
PRD765142 · Product
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 1000 mg/m2 milligram(s)/sq. meter
- Max total dose
- 4000 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BA01 — METHOTREXATE
- Marketing authorisation
- 42853
- MA holder
- EBEWE PHARMA
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB05101MIG · Substance
- Active substance
- Vincristine Sulfate
- Pharmaceutical form
- INJECTION
- Route of administration
- INTRAVENOUS BOLUS USE
- Max daily dose
- 4 mg milligram(s)
- Max total dose
- 48 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cytarabine STADA 100 mg/ml koncentrat till infusionsvätska, lösning
PRD1848083 · Product
- Active substance
- Cytarabine
- Substance synonyms
- ARA-C, CYTOSINE ARABINOSIDE
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 6000 mg/m2 milligram(s)/sq. meter
- Max total dose
- 12000 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BC01 — CYTARABINE
- Marketing authorisation
- 16727
- MA holder
- STADA ARZNEIMITTEL AG
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06859MIG · Substance
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 600 mg/m2 milligram(s)/sq. meter
- Max total dose
- 7200 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD7507295 · Product
- Active substance
- Etoposide
- Pharmaceutical form
- CAPSULE, SOFT
- Route of administration
- ORAL
- Max daily dose
- 200 mg/m2 milligram(s)/sq. meter
- Max total dose
- 3200 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01CB01 — ETOPOSIDE
- Marketing authorisation
- 10415
- MA holder
- CHEPLAPHARM ARZNEIMITTEL GMBH
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB01827MIG · Substance
- Active substance
- Doxorubicin Hydrochloride
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 50 mg/m2 milligram(s)/sq. meter
- Max total dose
- 200 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 21 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Etoposid Fresenius Kabi 20 mg/ml - koncentrat till infusionsvätska, lösning
PRD1982577 · Product
- Active substance
- Etoposide
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INFUSION
- Max daily dose
- 100 mg/m2 milligram(s)/sq. meter
- Max total dose
- 800 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01CB01 — ETOPOSIDE
- Marketing authorisation
- 47081
- MA holder
- FRESENIUS KABI AB
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Prednisolon Pfizer 10 mg tabletter
PRD495058 · Product
- Active substance
- Prednisolone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 50 mg/m2 milligram(s)/sq. meter
- Max total dose
- 2000 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB06 — PREDNISOLONE
- Marketing authorisation
- 10060
- MA holder
- PFIZER AB
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Nordimet 15 mg solution for injection in pre-filled pen
PRD4348203 · Product
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 15 mg milligram(s)
- Max total dose
- 120 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AX03 — -
- Marketing authorisation
- EU/1/16/1124/004
- MA holder
- NORDIC GROUP B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
MabThera 500 mg concentrate for solution for infusion
PRD2159886 · Product
- Active substance
- Rituximab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 375 mg/m2 milligram(s)/sq. meter
- Max total dose
- 3000 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XC02 — RITUXIMAB
- Marketing authorisation
- EU/1/98/067/002
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Dexametasona Krka 4 mg comprimidos
PRD4434320 · Product
- Active substance
- Dexamethasone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 15 mg/m2 milligram(s)/sq. meter
- Max total dose
- 660 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB02 — DEXAMETHASONE
- Marketing authorisation
- 5691639
- MA holder
- KRKA, D.D., NOVO MESTO
- MA country
- Portugal
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Karolinska University Hospital
- Sponsor organisation
- Karolinska University Hospital
- Address
- Eugeniavagen 3
- City
- Solna
- Postcode
- 171 64
- Country
- Sweden
Scientific contact point
- Organisation
- Karolinska University Hospital
- Contact name
- Björn Wahlin
Public contact point
- Organisation
- Karolinska University Hospital
- Contact name
- Björn Wahlin
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Sweden | Ongoing, recruiting | 183 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Sweden | 2024-11-08 | 2024-11-12 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-11-23 | Sweden | Acceptable with conditions 2024-03-04
|
2024-03-08 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-04-29 | Sweden | Acceptable 2024-07-05
|
2024-07-08 |