A Phase I/II Study of PBPC Mobilisation with VTP195183 Plus G-CSF Compared to Mobilisation with G-CSF Alone

Hematopoietic stem cells (HSC) are used to support the administration of high dose chemotherapy for a range of human cancers. For a safe HSC transplantation, a minimum of 5 million HSC per kilogram are required. HSC are collected from the bone marrow by using drugs such as G-CSF (filgrastim) which ‘mobilize’ them from the bone marrow into the bloodstream. HSC are collected from the bloodstream using an apheresis machine. Between 5 and 60% of patients fail to mobilize the minimum HSC dose required for safe transplantation, and this trial is investigating a way to enhance mobilization to overcome this problem. This trial aims to determine if a new vitamin A derivative is capable of enhancing HSC mobilization when used in conjunction with G-CSF. Patients will undergo two mobilization procedures. They will be given G-CSF alone, or a combination of the study drug plus G-CSF, and their stem cells will be collected. A comparison group of patients will be given G-CSF alone for both mobilizations. Stem cells collected from patients in this trial will be frozen and stored until they are required for transplantation into that patient. At that time, they will be monitored for how well they recover from their high dose chemotherapy and HSC transplantation.

Official Title

A Phase I/II Study of Peripheral Blood Progenitor Cells Mobilisation with VTP195183 Plus G-CSF Compared to Mobilisation with G-CSF Alone in Patients with Multiple Myeloma and Lymphoma.

Conditions

Study Type

Interventional

Study Design

Treatment, Randomized, Open Label, Active Control, Parallel Assignment

Further Details

Primary Outcomes: The primary objectives of this study are to determine:; 1. PBPC yield using the Retinoic Acid Receptor alpha (RARα) agonist VTP195183 plus G-CSF; 2. PB CD34+ kinetics using VTP195183 plus G-CSF; 3. PB CFU (colony) counts using VTP195183 plus G-CSF; 4. peripheral blood neutrophil protease levels using VTP195183 plus G-CSF; 5. The engraftment potential of human PBPC mobilized with VTP195183 plus G-CSF in a NOD-SCID/β2m-/- mouse modelSecondary Outcomes: The secondary objectives of this study are to determine:; 1. The toxicity of VTP195183 pretreatment when used with G-CSF; 2. The engraftment potential in the clinical transplant setting of autologous VTP195183 plus G-CSF mobilized PBPC after high dose chemotherapy for multiple myeloma and lymphoma (part 2)

Study Start

October 2005

Eligibility & Criteria

Ages Eligible for Study: 18 – 70 YearsGenders Eligible for Study: Both CriteriaInclusion Criteria:- Histologically proven multiple myeloma or lymphoma – Intent of treating physician to proceed to high dose therapy and autologous transplantation. – Not currently receiving thalidomide (within 1 week of commencing VTP195813 or G-CSF), cytotoxic agents or high dose prednisolone or Dexamethasone (at doses greater than 15mg prednisolone or equivalent per day). – Multiple myeloma patients must be taking regular bisphosphonate therapy – Absolute neutrophil count between 1.5 and 10 x 109/L – ECOG performance status 2 (Appendix 1) – Life expectancy of at least 2 months – Written informed consent signed by patient or legally authorized representative Exclusion Criteria:- Active infection or a fever 38.2C (fever due to B symptoms in lymphoma patients will not exclude a patient) – Use within the previous 30 days of other vitamin A preparations within the last 30 days (including oral vitamin supplements, oral retinoids for acne or other skin disorders, bexarotene or topical vitamin A preparations). – Pregnancy or breast feeding. Women of child-bearing potential, admitted to the trial must take adequate measures to prevent conception (at least two different forms of contraception during the study and for at least one month after completion of study drugs) and are to undergo a pregnancy test. – Significant non-malignant disease including HIV infection, uncontrolled hypertension (diastolic blood pressures > 115 mmHg), unstable angina. – Known allergy to E.coli-derived products – Current treatment with tetracycline antibiotics

Total Enrolment

30

Contact Details

Australia, VictoriaPeter MacCallum Cancer centre, Melbourne, Victoria, 3002, Australia; Recruiting Kirsten Herbert, MBBS Kirsten.Herbert@petermac.org Kirsten Herbert, MBBS, Principal Investigator