Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Intravenously over 1 hour daily for 5 days, every 3 weeks.

PM00104

Roger Bryan Cohen, MD

Eunice Lee Kwak, MD

Phase I trial, dose escalating, prospective, open-label, non-randomized, multicenter study. The purpose is to determine the safety, tolerability, dose limiting toxicity (DLT) and recommended dose (RD) of PM00104, administered intravenously over 1 hour daily for 5 days every 3 weeks (this is considered as 1 cycle) to subjects with advanced malignant solid tumors or lymphoma.

Phase I trial, dose escalating, prospective, open-label, non-randomized, multicenter study. The purpose is to determine the safety, tolerability, dose limiting toxicity (DLT) and recommended dose (RD) of PM00104, administered intravenously over 1 hour daily for 5 days every 3 weeks (this is considered as 1 cycle) to subjects with advanced malignant solid tumors or lymphoma. Secondary objectives are to determine the preliminary pharmacokinetics of PM00104, to evaluate the relationship between pharmacokinetics/pharmacodynamics and to evaluate the preliminary antitumor activity of PM00104. Dose-escalation guidelines will follow an accelerated phase I design for conventional cytotoxic agents in order to minimize the number of subjects treated at the subtoxic dose levels. The trial will be conducted in compliance with the protocol, Good clinical practice (GCP) and applicable regulatory requirements.

A Phase I Study of Zalypsis (PM00104) in Subjects With Advanced Malignant Solid Tumors or Lymphoma

A Phase I Multicenter, Open-label, Dose-escalating Clinical and Pharmacokinetic Study of PM00104 Administered Intravenously Over 1 Hour Daily for 5 Days, Every 3 Weeks, to Subjects With Advanced Malignant Solid Tumors or Lymphoma.

DLTs were defined as follows:

* Hematological adverse events:

  * Any grade 4 neutropenia (absolute neutrophil count (ANC) \< 0.5 x109/l) for longer than five days;
  * Any grade 4 neutropenia accompanied by fever (at least 38.5°C);
  * Any grade 4 neutropenia and sepsis or other severe infection;
  * Any grade 4 thrombocytopenia.
* Any other grade 3/4 non-hematological adverse event (AE) and any increase of cardiac troponin I ≥0.1 ng/ml together with evidence of cardiac damage by electrocardiogram (ECG) or echocardiogram (ECHO), except for untreated nausea/vomiting or hypersensitivity reactions.
* Decrease in left ventricular ejection fraction (LVEF) \> 20% compared to the patient's baseline value and/or LVEF \< 50% below normal limits for the institution.
* Delay in the initiation of a subsequent dose exceeding two weeks due to drug related AEs

Best tumor response was defined as the best response achieved during the study according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response (CR): disappearance of all lesions; Partial response (PR): ≥10% decrease in target lesion size or ≥15% decrease in tumor density; Disease progression (PD): ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; Stable disease (SD): none of the CR, PR, or PD criteria met; RECIST,

PharmaMar

All patients treated with PM00104 were evaluable for safety

All patients were to receive treatment for at least one 3-week cycle, which consisted of PM00104 administrations daily for 5 days and all study evaluations up to the next treatment cycle. Cycles were to be repeated every three weeks until disease progression, unacceptable toxicity, intercurrent serious illness, withdrawal of informed consent by the patient, Investigator's opinion, or treatment delay \> 2 weeks. Patients were considered to be on study for the duration of their treatment and for the first 30 days following treatment discontinuation, defined as the day of the last PM00104 administration

Dose-level I

Dose-level II

Dose-level III

Dose-level IV

Dose-level V

Total

Age, Continuous

Sex: Female, Male

Caucasian

Asian

Race/Ethnicity, Customized

PS 0

PS 1

Eastern Cooperative Oncology Group (ECOG) performance status (PS). 0 Fully active, able to carry on all pre-disease performance without restriction; 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2 Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours; 3 Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours; 4 Completely disabled; cannot carry on any selfcare; totally confined to bed or chair; 5 Dead

ECOG PS

Primary tumor

Prior chemotherapy

Prior Surgery

Prior radiotherapy

This phase I study was prematurely closed due to a low recruiting rate as well as to the perception that this could be an unpractical dosing schedule when compared to other schedules evaluated in the clinical development program of PM00104.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase I Study of Zalypsis (PM00104) in Subjects With Advanced Malignant Solid Tumors or Lymphoma	NCT00359294	Solid Tumors Lymphoma	PM00104	18 Years -	PharmaMar
A Phase I Study of Zalypsis (PM00104) in Subjects With Advanced Malignant Solid Tumors or Lymphoma	NCT00359294	Solid Tumors Lymphoma	PM00104	18 Years -	PharmaMar

Spots Global Cancer Trial Database for pm00104

Every month we try and update this database with for pm00104 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pm00104

Every month we try and update this database with for pm00104 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pm00104 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.