Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Hematologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Tezacitabine

Enzyme Inhibitors

Tezacitabine as a bolus infusion daily x 5

Tezacitabine (FMdC)

Stefan Faderl, MD

The goal of this clinical research study is to find the highest dose of Tezacitabine (FMdC) which can be safely given as a continuous infusion by vein to patients with hematologic malignancies. The general safety and effectiveness of this drug will also be studied.

Patients with leukemias that have relapsed from previous therapies have a low cure rate. Hence the need to discover new antileukemic agents. Tezacitabine is a nucleoside analogue with equivalent or even superior activity when compared with ara-C in leukemic cell lines. It has shown significant antitumor activity in vitro and in vivo tumor models. Several phase I studies with various dosing schedules have been conducted in solid tumors where the dose-limiting toxicity (DLT) is mainly myelosuppression, usually a favorable feature for development of leukemia. In a phase I study in hematological malignancies, we used Tezacitabine as a bolus infusion daily x 5. The DLT consisted of grade 3 CNS toxicities and mucositis in 3/6 patients. The study is ongoing and we are currently evaluating a dose level of 7.5 mg/m2 as possible Maximum Tolerated Dose (MTD). However, in view of the fact that tezacitabine is a cell cycle specific agent with a short terminal plasma half-life of 2 to 6 hours, a continuous infusion dosing schedule may enhance the activity and reduce the incidence of adverse effects of tezacitabine.

Phase I Study of Continuous Infusion Schedule of FMdC in Hematologic Malignancies

Phase I Study of Continuous Infusion Schedule of (E)-2'-Deoxy-2'-(Fluoromethylene) Cytidine (Tezacitabine, FMdC) in Hematologic Malignancies

MTD determination made from dose level without a dose-limiting toxicity (DLT)

Chiron Corporation

M.D. Anderson Cancer Center

Immune System Diseases

Infections

Symptoms and General Pathology

Rare Diseases

Lymphoma

Leukemia

Leukemia, Lymphoid

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Mycoses

Leukemia, Lymphocytic, Chronic, B-Cell

Mycosis Fungoides

Lymphoma, T-Cell, Cutaneous

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Cutaneous T-cell Lymphoma

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Adenosine

Pentostatin

Patients received Deoxycoformycin (DCF)/Pentostatin administered by intravenous bolus daily over a consecutive 3-day period. This course was repeated at 3-week intervals.

Deoxycoformycin (DCF)

Razelle Kurzrock, MD

The purpose of this study is to determine the side effects and antitumor response of patients with lymphoid malignancies to Deoxycoformycin (DCF)/Pentostatin.

Deoxycoformycin(DCF)/Pentostatin is a T-cell cytotoxic drug with previously reported responses in lymphoid malignancies but larger studies are needed.

A Study Of Deoxycoformycin(DCF)/Pentostatin In Lymphoid Malignancies

A Phase II Study of Deoxycoformycin (DCF) in Lymphoid Malignancies

Overall responses (OR) of participants with lymphoid malignancies to Deoxycoformycin (DCF)/Pentostatin defined as Complete Response (CR) and Partial Response (PR).

Cohort 1, Schedule A, NUC-1031 I.V. 1000mg/m2, Days 1, 8, \& 15 every 28 days Cohort 1, Schedule B, NUC-1031 I.V. 500mg/m2, Days 1 \& 5, 8 \& 12, 15 \&19 every 28 days Cohort 2, Schedule A, NUC-1031 I.V. 2000mg/m2, Days 1, 8, \& 15 every 28 days Cohort 2, Schedule B, NUC-1031 I.V. 1000mg/m2, Days 1 \& 5, 8 \& 12, 15 \&19 every 28 days

NUC-1031

Dr Blagden, PhD FRCP

This is a two-part Phase I, open label, dose-escalation, study of NUC-1031 as a single agent in patients with advanced solid tumours who have failed to respond to or who have relapsed after treatment with standard therapy. NUC-1031 is a ProTide of gemcitabine, a drug that has been used widely and effectively against cancers for many years. Both NUC-1031 and gemcitabine work by preventing cancer cells from dividing by attacking their DNA (deoxyribonucleic acid). Non clinical studies have shown that NUC-1031 is more effective than gemcitabine because it is able to reach cancer cells by passive diffusion, is less easily degraded by the cancer cell, and delivers the monophosphate form of the active agent. The first part of the study is to determine recommended phase 2 dose by dose escalation and the second part is to explore preliminary anti-tumour activity.

This is a two-part, Phase I, open label study of NUC-1031 as a single agent, administered IV weekly on days 1, 8, \& 15 (Schedule A) or twice weekly on days 1 \& 5, 8 \& 12, 15 \&19 (Schedule B) of a 28 day- cycle regimen. An initial dose-escalation phase (Part I) will be followed by an expansion cohort phase (Part II) using the preferred regimen from Part I. In Part I, sequential patients will be assigned to increasing doses of NUC-1031 in a standard '3 + 3' design to determine the recommended Phase II dose (RP2D). There will be a review of all available data (in particular the safety profile and preliminary PK data through to at least the last scheduled day of Cycle 1) following enrolment of the second cohort of both schedule A and B to select the preferred administration schedule to take forward for ongoing evaluation.

In Part II (dose expansion) additional patients will be enrolled to receive NUC-1031 at the RP2D and dosing frequency determined from Part I of the study. During Part II, further information will be obtained regarding safety, PK, PD and preliminary anti-tumour efficacy of NUC-1031 at RP2D.

In both parts of the study, patients may continue to receive NUC-1031 for up to 6 cycles, until disease progression, for as long as the participant receives clinical benefit in the opinion of the CI, the occurrence of unmanageable drug related toxicity despite dose modification or if the study participant declines further treatment.

NUC-1031 in Patients With Advanced Solid Tumours

A Two-part, Phase I Open Label Dose-escalation Study to Assess the Safety, Pharmacokinetics and Clinical Activity of NUC-1031, a Nucleotide Analogue, in Patients With Advanced Solid Tumours.

Adverse events (AE) and changes from baseline in vital signs, clinical laboratory parameters, and electrocardiography (ECG) assessments will be assessed

Adverse events (AE) and changes from baseline in vital signs, clinical laboratory parameters, and electrocardiography (ECG) assessments

PK endpoints will include assessments such as systemic Clearance (CL), Apparent Volume of Distribution (Vd), Area Under the Curve (AUC), Maximum plasma (peak) drug concentration after single dose administration (Cmax), and t1/2.

Assessment of anti-tumour activity as defined by RECIST version 1.1

Urinary excretion of NUC-1031 and metabolites.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Study of Continuous Infusion Schedule of FMdC in Hematologic Malignancies	NCT00061620	Hematologic Mal...	Tezacitabine (F...	15 Years -	M.D. Anderson Cancer Center
A Study Of Deoxycoformycin(DCF)/Pentostatin In Lymphoid Malignancies	NCT00038025	Peripheral T-ce... Cutaneous T-cel... Chronic Lymphoc...	Deoxycoformycin...	16 Years -	M.D. Anderson Cancer Center
NUC-1031 in Patients With Advanced Solid Tumours	NCT01621854	Cancer	NUC-1031	18 Years -	Imperial College London

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