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 aggressive non-Hodgkin’s Lymphoma.
- Conditions
- Aggressive non-Hodgkin’s Lymphoma.For aggressive NHL patient cure is still the target of therapy and a CR is a prerequisite to achieve this goal. Salvage therapy needs more aggressive experimental treatment approaches including high-dose chemo-immunotherapy plus hematopoietic autologous stem cell transplantation, and in selected cases, allogeneic stem-cell transplantation.
- Registration Number
- EUCTR2004-001117-34-ES
- Lead Sponsor
- Pharma Mar S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 0
1.Written informed consent obtained before starting any study-specific procedure.
2. Histologically confirmed aggressive lymphomas, including the following:
2.1 B-Cell neoplasms.
2.1.1 Precursor B-cell neoplasm
2.1.1.1.1 Precursor B-lymphoblastic lymphoma
2.1.2 Mature (peripheral) B-cell neoplasms
2.1.2.1. 1 Follicular lymphoma (histologic conversion)
2.1.2.1. 2 Mantle-cell lymphoma (diffuse pattern or blastic variant)
2.1.2.1. 3 Diffuse large B-cell lymphoma
2.1.2.1. 4 Mediastinal large B-cell lymphoma
2.1.2.1. 5 Burkitt’s lymphoma/Burkitt cell leukemia
2.2 T-cell and NK-cell neoplasms
2.2.1 Precursor T-cell neoplasm
2.2.1.1.1 Precursor T-lymphoblastic lymphoma
2.2.2 Mature (peripheral) T-cell neoplasms
2.2.2.1.1 Aggressive NK-cell leukemia
2.2.2.1.2 Adult T-cell lymphoma/leukemia (HTLV1)
2.2.2.1.3 Extranodal NK/T-cell lymphoma, nasal type
2.2.2.1.4 Enteropathy-type T-cell lymphoma
2.2.2.1.5 Hepatosplenic gamma-delta T-cell lymphoma
2.2.2.1.6 Subcutaneous panniculitis-like T-cell lymphoma
2.2.2.1.7 Anaplastic large-cell lymphoma, T/null cell, primary cutaneous type
2.2.2.1.8 Peripheral T-cell lymphoma, not otherwise characterized
2.2.2.1.9 Angioimmunoblastic T-cell lymphoma
2.2.2.1.10 Anaplastic large-cell lymphoma, T/null cell, primary systemic type
3. Patient requires treatment because NHL relapses following a response to standard chemotherapy or high dose chemotherapy , or NHL is refractory (i.e. failure to achieve al least CR, PR or SD) to its more recent chemotherapy.
4. Prior autologous and/or allogeneic stem cell transplantation is allowed. In case of allogeneic hematopoietic stem cell transplantation (HSCT), patient has to be off immunosuppressive agents before he can enrolled.
5. 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
6. Recovery from any non-hematological toxicity derived from previous treatments. The presence of alopecia and NCI-CTC grade < 2 symptomatic peripheral neuropathy is allowed.
7. Age > 18 years.
8. Performance status (ECOG) < 2 (Appendix 2)
9. Adequate renal, hepatic, and bone marrow function (assessed < 14 days before inclusion in the study):
oNeutrophil count ³ 1.5 x 109/L
oPlatelet count ³ 100 x 109/L
oHaemoglobin ³ 8.0 g/dL
oCreatinine clearance ³ 40 ml/min (calculated from the Cockcroft and Gault formula, Appendix 3)
oSerum bilirubin * 1.5 mg/dL and alkaline phosphatase * 2.5 x ULN (< 5 x ULN in case of extensive bone involvement)
oAST, ALT < 2.5 x ULN (< 5 x ULN in case of liver involvement).
oAlbumin > 25 g/L
10. 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
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. Acute lymphoblastic leukemia.
4. CNS lymphoma.
5. HIV-associated lymphoma.
6. Prior gene therapy with viral vectors.
7. More than three previous lines of systemic biological agents or chemotherapies. (Bone marrow or stem cell transplantation as consolidation therapy of a previous response is understood as one line of chemotherapy).
8. Wash-out periods since the end of the precedent therapy less than:
o6 weeks for nitroso-urea or high dose chemotherapy
o4 weeks for other chemotherapies or biological agents
o4 weeks for radiation or radionuclide therapy (6 weeks in case of prior extensive external beam radiation (more than 25% of bone marrow distribution).
o4 weeks for major prior surgery
o30 days for any investigational product
o4 weeks for immunosuppressive therapy after allogeneic hematopoietic stem cell transplantation.
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):
·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,
·Patient or patient’s partner physical sterilization; or,
·One of the following, for female patients or female partner of male patients:
oImplants of levonorgestrel; or,
oInjectable progestogen; or,
oOral 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,
oAny 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,
oDouble barrier method (2 physical barriers or 1 physical barrier plus spermicide); or,
oAny 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:
oNon-melanoma skin cancer
oCarcinoma in situ of any site
oAny other cancer curatively treated and no evidence of disease for at least 10 years.
12. Known cerebral or leptomeningeal involvement.
13. Other relevant diseases or adverse clinical conditions:
oCongestive heart failure or angina pectoris, myocardial infarction within 12 months before inclusion in the study.
oUncontrolled arterial hypertension (i.e. current arterial diastolic blood pressure over 100 mmHg).
oUncontrolled cardiac supraventricular arrhythmias (i.e. requiring a change in medication within the last 3 months or a hospital admission within the past 6 months).
oCardiac ventricular arrhythmia.
oHistory of significant neurological or psychiatric disorders
oActive infection; infection by HIV, HBV or HCV
oMyopathy or any clinical situation that causes significant and persistent elevation of CK (>2.5 ULN in two different determinations performed with one week appart)
oSignificant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis)
oUncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method