A Phase II Multicenter,Open-Label, Clinical And Pharmacokinetic Study Of Aplidin® As A 1-Hour Weekly IV Infusion, In Patients With Relapsed Or Refractory Indolent Non-Hodgkin’s Lymphoid Neoplasms.

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2004-002692-16-ES
• Date of registration: 30/03/2005
• Prospective Registration: No
• Primary sponsor: PharmaMar SA unipersonal
• Public title: A Phase II Multicenter,Open-Label, Clinical And Pharmacokinetic Study Of Aplidin® As A 1-Hour Weekly IV Infusion, In Patients With Relapsed Or Refractory Indolent Non-Hodgkin’s Lymphoid Neoplasms.
• Scientific title: A Phase II Multicenter,Open-Label, Clinical And Pharmacokinetic Study Of Aplidin® As A 1-Hour Weekly IV Infusion, In Patients With Relapsed Or Refractory Indolent Non-Hodgkin’s Lymphoid Neoplasms.
• Date of first enrolment: 27/10/2004
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-002692-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): Therapeutic use (Phase IV):

Countries of recruitment

Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent obtained before starting any study-specific procedure..
2. Histologically confirmed indolent lymphoid neoplasms, including the following:
2.1. Mature (peripheral) B-cell neoplasms
· B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma
· B-cell prolymphocytic leukemia
· Lymphoplasmacytic lymphoma
· Splenic marginal zone B-cell lymphoma (1/2 villous lymphocytes)
· Hairy cell leukemia
· Extranodal marginal zone B-cell lymphoma of MALT type
· Nodal marginal zone B-cell lymphoma (1/2 monocytoid B cells)
· Follicular lymphoma (except large cell)
· Mantle-cell lymphoma (except diffuse pattern or blastoid variant)
2.2 Mature (peripheral) T-cell neoplasms
· T-cell prolymphocytic leukemia
· T-cell granular lymphocytic leukemia
· Mycosis fungoides/Sezary syndrome
3. The lymphoproliferative malignancy either relapses following a response to standard or high-dose chemotherapy , or is refractory to previous chemotherapy and there is a clinical need to start a new chemotherapy.
3.1. Relapsed disease is defined as development of any of the following after a prior response of at least 6 months duration:
· Lymphadenopathy
· Splenomegaly
· Malignant lymphocytosis greater than 5000 x 109/L
· Infiltration of the bone marrow with malignant lymphocytes
3.2. Refractory disease
· No partial response (PR) to prior therapy OR
· Complete response or PR of less than 6 months duration
4. Disease is measurable: existence of a bidimensional lesion greater than 2 cm in its longer diameter or malignant lymphocytosis greater than 5000 x 109/L
5. Recovery from any non-hematological toxicity derived from previous treatments. The presence of alopecia and NCI-CTC grade < 2 symptomatic peripheral neuropathy is allowed.
6. Age > 18 years.
7. Performance status (ECOG) < 2 (Appendix 4)
8. Adequate renal, hepatic, and bone marrow function (assessed < 14 days before inclusion in the study):
8.1. Neutrophil count ³ 1.5 x 109/L
8.2. Platelet count ³ 100 x 109/L
8.3. Haemoglobin ³ 8.0 g/dL
8.4. Creatinine clearance ³ 40 ml/min (calculated from the Cockcroft and Gault formula, Appendix 5)
8.5. Serum bilirubin * 1.5 mg/dL and alkaline phosphatase * 2.5 x ULN (< 5 x ULN in case of extensive bone metastases)
8.6. AST, ALT < 2.5 x ULN (< 5 x ULN in case of liver metastasis).
8.7. Albumin > 25 g/L
9. Left ventricular ejection fraction within normal limits.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Prior therapy with Aplidin®.
2. Concomitant therapy with any anti-lymphoproliferative agent, including glucocorticoids at a daily dose greater than 10 mg prednisone or equivalent, except when they were indicated for symptom control and disease progression was documented while on esteroids.
3. Aggressive histological conversion.
4. HIV-associated lymphoma
5. CNS lymphoma
6. More than five previous lines of systemic biological agents or chemotherapies.
7. Prior gene therapy with viral vectors.
8. Wash-out periods since the end of the precedent therapy less than:
8.1. 6 weeks for nitroso-urea or high dose chemotherapy
8.2. 4 weeks for other chemotherapies or biological agents
8.3. 4 weeks for radiation or radionuclide therapy (6 weeks in case of prior extensive external beam radiation (more than 25% of bone marrow distribution).
8.4. 4 weeks for major prior surgery
8.5. 30 days for any investigational product
9. Pregnant or lactating women.
10. Men and women of reproductive potential who are not using effective contraceptive methods (one or more of the following):
10.1. Complete abstinence from intercourse from 2 weeks prior to administration of the study drug, throughout the study, and for at least 6 months after completion or premature discontinuation from the study to account for elimination of the investigational drug; or,
10.2. Patient or patient’s partner physical sterilization; or,
10.3. One of the following, for female patients or female partner of male patients:
· Implants of levonorgestrel; or,
· Injectable progestogen; or,
· Oral contraceptive (combined or progestogen only; subject taking oral contraceptives should have been on a stable regimen for at least 2 months prior to screening),or,
· Any intrauterine device (IUD) with published data showing that the lowest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or,
· Double barrier method (2 physical barriers or 1 physical barrier plus spermicide); or,
· Any other method with published data showing that the lowest expected failure rate for that method is less than 1% per year.
11. History of another neoplastic disease. The exceptions are:
11.1. Non-melanoma skin cancer
11.2. Carcinoma in situ of any site
11.3. Any other cancer curatively treated and no evidence of disease for at least 10 years.
12. Known symptomatic cerebral or leptomeningeal involvement.
13. Other relevant diseases or adverse clinical conditions:
13.1. Congestive heart failure or angina pectoris, myocardial infarction within 12 months before inclusion in the study.
13.2. Uncontrolled arterial hypertension (i.e. current arterial diastolic blood pressure over 100 mmHg).
13.3. Uncontrolled cardiac supraventricular arrhythmias (i.e. requiring a change in medication within the last 3 months or a hospital admission within the past 6 months).
13.4. Cardiac ventricular arrhythmia.
13.5. History of significant neurological or psychiatric disorders
13.6. Active infection; infection by HIV, HBV or HCV
13.7. Myopathy or any clinical situation that causes significant and persistent elevation of CK (>2.5 ULN in two different determinations performed with one week appart)
13.8. Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis)
13.9. Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months)
14. Treat

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non-Hodgkin’s Lymphomas (NHLs) relapsing or refractory

Intervention(s)

Product Name: Aplidin
Product Code: APLD
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: Cyoctodepsin
CAS Number: 137219-37-5
Current Sponsor code: APLD
Other descriptive name: Aplidine
Concentration unit: mg/l milligram(s)/litre
Concentration number: 0.5 -
INN or Proposed INN: Cyoctodepsin
CAS Number: 137219-37-5
Current Sponsor code: APLD
Other descriptive name: Aplidin
Concentration unit: mg/l milligram(s)/litre
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Main Objective: · To assess the anti-tumor activity of Aplidin® given as a 1-hour weekly IV infusion, in patients with Indolent non-Hodgkin’s Lymphoid neoplasm, relapsing or refractory to a prior therapy

Primary end point(s): Objective response rate (CR/CRu+PR/nPR)

Secondary Objective: · To further investigate the safety profile of Aplidin® given as 1-hour weekly IV infusion in this patient population.
· To obtain additional pharmacokinetic information for Aplidin® given as 1-hour weekly IV infusion in patients with indolent non-Hodgkin’s Lymphoid neoplasm (NHL).

Secondary ID(s)

APL-B-012-02

Ethics review

Status: Approved
Approval date: 24/06/2004
Contact:

Results

• Results available: Yes
• Date Posted: 05/08/2016
• Date Completed: 20/11/2007
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2004-002692-16/results