ATRA Plus G-CSF for Mobilization of Hematopoietic Stem and Progenitor Cells

Multiple Myeloma Clinical Trial

Official title:

A Phase I Study of Haematopoietic Stem Cell Mobilization Using G-CSF With ATRA in Patients With Cutaneous Lymphoma and Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00400556
• Other study ID #: 04/24
• Status: Completed
• Phase: Phase 1
• First received: November 15, 2006
• Last updated: November 15, 2006
• Start date: March 2005
• Est. completion date: May 2005

Study information

• Verified date: November 2006
• Source: Peter MacCallum Cancer Centre, Australia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

Hematopoietic stem and progenitor cells (HSPC) are used for transplantation in patients undergoing high dose therapy for the treatment of a range of cancers.

• HSPC are collected from the bloodstream after treatment with medications that cause the HSPC to move from the bone marrow into the bloodstream, a process called mobilization

• between 5 and 60% of patients can fail to collect enough HSPC for a transplant, using current mobilization techniques

• this study aims to assess the safety of combining a derivative of vitamin A, ATRA with G-CSF (the drug most commonly used to mobilize HSPC)

• ATRA has never been combined with G-CSF for mobilization of HSPC and therefore a study is needed to assess the safety of this combination, and whether it successfully mobilizes HSPC

Description:

HSPC mobilization is normally achieved using cytokines such as G-CSF, or occasionally GM-CSF, often in combination with myelosuppressive chemotherapy.

Studies in the mouse model have shown that retinoids (vitamin A derivatives) can be combined with G-CSF, and that this combination synergizes to enhance HSPC mobilization over that seen with G-CSF alone.

This trial aims to assess the safety and mobilization efficacy of combining mobilizing doses of G-CSF with a standard dose of ATRA, using a treatment regimen derived from the earlier murine studies.

In this phase I pilot study, six patients with multiple myeloma or cutaneous lymphoma will be treated with ATRA plus G-CSF, and safety and toxicity data collected for the two week study drug period plus a further two weeks' follow-up. The primary endpoint is safety and toxicity, the secondary endpoint is an observation of the mobilization efficacy as demonstrated by CD34+ cell counts over the study period. Patients will not undergo stem cell collection during this study, as this is purely an observational study. Participating patients will not be those who would normally be scheduled for stem cell collection and transplantation in the near future, but rather patients with stable disease who are not candidates for imminent transplantation, or who have collected adequate HSPC on previous mobilization attempts and are currently being observed.

Cutaneous lymphoma and multiple myeloma are chosen as suitable disease states for this study as there is in vitro evidence of a possible disease benefit of retinoids in these disorders. If disease response is noted during the study or follow up period, ongoing ATRA will be offered at the discretion of the treating physician.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: May 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• likely to comply with study protocol

• age of 18-70

• histologically proven multiple myeloma or lymphoma

• not currently receiving cytotoxic agents however thalidomide, prednisolone, dexamethasone are allowable

• multiple myeloma patients must be receiving regular bisphosphonates

• absolute neutrophil count between 1.5 and 10.0 x 10^9/L

• ECOG performance status </= 3

• life expectancy of at least two months

• written informed consent signed by patient or legally authorised representative

Exclusion Criteria:

• use of other vitamin A preparations within the last 30 days

• active infection or fever >/= 38.2 degrees celsius

• 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) and are to undergo a pregnancy test. Oral contraception must not include low-dose progestogens

• known allergy to E.coli derived products

• current treatment with tetracycline antibiotics

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cutaneous Lymphoma
• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• ATRA plus G-CSF (filgrastim, NEUPOGEN (R)) combination

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Center	East Melbourne	Victoria

Sponsors (2)

Lead Sponsor	Collaborator
Peter MacCallum Cancer Centre, Australia	The Leukemia and Lymphoma Society

Country where clinical trial is conducted

Australia, 

References & Publications (1)

Herbert KE, Walkley CR, Winkler IG, Hendy J, Olsen GH, Yuan YD, Chandraratna RA, Prince HM, Lévesque JP, Purton LE. Granulocyte colony-stimulating factor and an RARalpha specific agonist, VTP195183, synergize to enhance the mobilization of hematopoietic progenitor cells. Transplantation. 2007 Feb 27;83(4):375-84. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity data (NCI-CTC version 2.0 criteria)
Primary	skin toxicity
Primary	hepatotoxicity
Primary	mucosal toxicity
Primary	hematologic toxicity
Primary	neurologic toxicity
Primary	treatment response
Primary	CD34+ cell count peak level
Primary	time to CD34+ count peak level
Primary	time to reach level >5 x 10^6.L
Primary	area under curve for duration of time spent with CD34+ count >5 x 10^6/L
Primary	peripheral blood colony forming unit assays
Primary	peak CFU-GEMM level
Primary	time to peak CFU-GEMM level