Study of Pixantrone in CD20+ Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma

Aggressive Non-Hodgkin Lymphoma Clinical Trial

Official title:

A Multicentre, Phase II, Open Label, Single Arm Study of Pixantrone in Patients With CD20-positive Relapsed or Refractory Aggressive Non-Hodgkin Lymphoma Treated With Rituximab, Ifosfamide and Etoposide.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03458260
• Other study ID #: PIVeR
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 26, 2018
• Est. completion date: March 2025

Study information

• Verified date: September 2023
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy of Pixantrone with rituximab, ifosfamide and etoposide as measured by the overall metabolic response rate after 2 cycles of treatment or at permanent treatment discontinuation.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 74
• Est. completion date: March 2025
• Est. primary completion date: June 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically proven CD20+ aggressive non-Hodgkin lymphoma (diffuse large B-cell lymphoma (DLBCL), de novo or transformed DLBCL from previously untreated low grade non-Hodgkin lymphoma or grade 3b follicular lymphoma) as per the World Health Organization (WHO) 2016 criteria

2. Relapsed or refractory disease, defined as follows:

1. Patients eligible for ASCT who failed to achieve a Complete Response (CR) after at least one salvage therapy (eg, Rituximab-Etoposide- Methylprednisolone - Cytarabine - Cisplatin (R-ESHAP) or Rituximab- Dexamethasone- High-dose Cytarabine - Cisplatin (R-DHAP), patients who were previously refractory to Rituximab-Ifosfamide-Cytarabine-Etoposide (R-ICE) (stable disease or progressive disease) are not eligible to the study)

2. Or patients in first relapse after Autologous Stem Cell Transplant (ASCT)

3. Or patients not eligible for ASCT who failed to achieve a CR after at least one prior treatment (and no more than 4 previous lines) or in relapse after at least one prior treatment (and no more than 4 previous lines).

3. Age > or =18 years

4. Eastern Cooperative Oncology Group (ECOG) performance status < or = 2

5. Subjects must have evaluable disease based on positron emission tomography (PET-CT) scan

6. Minimum life expectancy of 6 months

7. Signed written informed consent

8. Patient covered by any social security system

9. Men must agree to use a barrier method of contraception during the treatment period and until 6 months after the last dose of chemotherapy

10. Women of childbearing potential must agree to use an adequate method of contraception, such as oral contraceptives, intrauterine device, or barrier method of contraception during the treatment period and until 12 months after the last dose of chemotherapy

Exclusion Criteria:

1. Any other histological type of lymphoma (Burkitt lymphoma, mantle-cell lymphoma…)

2. Any history of previously treated indolent non-Hodgkin lymphoma

3. Symptomatic central nervous system or meningeal involvement by the lymphoma

4. Contraindication to any drug contained in the Pixantrone with rituximab, ifosfamide and etoposide regimen

5. Treatment with any investigational drug within 28 days before the first study drug administration

6. Any of the following lab abnormalities unless related to the lymphoma or bone marrow

infiltration:

1. Absolute neutrophil count (ANC) < 1.0 G/L

2. Platelet count < 100 G/L

3. Creatinine clearance < 40 mL/min for patients < 70 y, or creatinine clearance < 60 mL/min for patients > or = 70 y, by Modification of Diet in Renal Disease (MDRD) method.

4. Total bilirubin level > 1,5 x Upper Limit of Normal (ULN)

5. Serum ASpartate Transaminase (AST) or ALanine Transaminase (ALT)> 2,5x ULN

7. Known Human Immunodeficiency Virus (HIV) positive

8. Active hepatitis C virus (HCV) (Positive HCV serology with positive Polymerase Chain Reaction (PCR) for HCV RNA)

9. Active hepatitis B (HB) :

1. HBsAg positive

2. HBsAg negative, Ac anti-HBs positive and/or Ac anti-HB core (HBc) positive (Patients who are seropositive due to a history of hepatitis B vaccine are eligible. Patients with Ac anti-HBs positive and/or Ac anti-HBc positive and no history of hepatitis B vaccine are eligible only if PCR for HB virus DNA is negative)

10. Cumulative dose of doxorubicine or equivalent > 450mg/m2

11. Left ventricular ejection fraction (LVEF) < 50% measured by echocardiography or isotopic method

12. Congestive heart failure (any stage from New York Heart Association (NYHA) classification)

13. Uncontrolled arterial hypertension

14. Severe rhythmic heart disease

15. Uncontrolled ischemic heart disease, including patients with stable angina

16. Significant valvular heart disease

17. History of a myocardial infarction within 6 months prior to enrolment

18. Pregnant or lactating females

19. Prior history of malignancies with the exception of non-melanoma skin tumors (basal cell or squamous cell carcinoma) or in situ cervical carcinoma

20. Any serious active disease or co-morbid medical condition according to the investigator's decision

21. Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness

22. Use of any standard or experimental anti-cancer drug therapy within 28 days before the first study drug administration

23. Use of corticosteroids prior to baseline PET-CT

24. Person deprived of his/her liberty by a judicial or administrative decision

25. Person hospitalized without consent

26. Adult person under legal protection

Related Conditions & MeSH terms

• Aggression
• Aggressive Non-Hodgkin Lymphoma
• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Pixantrone
6 cycles - dose = 80mg/m²

Other:
• Ifosfamide
6 cycles - 1500 mg/m2
• Etoposide
6 cycles - 150 mg/m2
• Rituximab
6 cycles - 375 mg/m2

Procedure:
• Transplant
after 2 or 6 cycles

Locations

Country	Name	City	State
Belgium	AZ Sint Jan	Brugge
Belgium	Institut Jules Bordet - Centre des tumeurs de l'ULB	Brussels
Belgium	Centre Hospitalier de Jolimont	Haine-Saint-Paul
France	CH d'Avignon	Avignon
France	Centre Hospitalier de la Côte Basque	Bayonne
France	CHU Jean Minjoz	Besançon
France	Hôpital Haut-Lévèque	Bordeaux
France	Centre Hospitalier William Morey	Chalon-sur-Saône
France	Clinique Victor Hugo	Le Mans
France	CHRU de Lille	Lille
France	CHU Lyon Sud	Lyon
France	CHU de la Conception	Marseille
France	Centre Lacassagne	Nice
France	Hopital La Pitié Salpétriere	Paris
France	Hôpital St louis	Paris
France	CHU de Poitiers	Poitiers
France	Centre Hospitalier Annecy Genevois	Pringy
France	CH de Cornouaille	Quimper
France	Hôpital Robert Debré	Reims
France	CHU de Rouen	Rouen
France	CHU de Strasbourg	Strasbourg
France	CHU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Metabolic Response rate (OMR) according to local investigator	by local investigator according to Lugano classification 2014	After 42 days of treatment (2 cycles) or at permanent treatment discontinuation.
Secondary	Complete Metabolic Response rate (CMR) according to local investigator	according to local investigator	After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
Secondary	Overall Metabolic Response rate (OMR) according to central review	according to local investigator	After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
Secondary	Complete Metabolic Response rate (CMR) according to central review	according to local investigator	After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
Secondary	Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)		After 42 or 126 days of treatment (2 or 6 cycles of 21 days) or at permanent treatment discontinuation.
Secondary	Number of patients for whom Partial Metabolic Response (PMR) is transformed into CMR		After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
Secondary	Rate of ASCT	Number of patients who perform an ASCT out of total number of patients	After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
Secondary	Success of stem cell collection after treatment	Rate of successful stem cell collection	After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.