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

November 15, 2006 updated by: Peter MacCallum Cancer Centre, Australia

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • Peter MacCallum Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peter MacCallum Cancer Centre, Australia

Collaborators

The Leukemia and Lymphoma Society

Investigators

  • Principal Investigator: Kirsten E Herbert, MBBS, Peter MacCallum Cancer Center
  • Principal Investigator: Miles Prince, MBBS, Peter MacCallum Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Study Completion

May 1, 2005

Study Registration Dates

First Submitted

November 15, 2006

First Submitted That Met QC Criteria

November 15, 2006

First Posted (Estimate)

November 17, 2006

Study Record Updates

Last Update Posted (Estimate)

November 17, 2006

Last Update Submitted That Met QC Criteria

November 15, 2006

Last Verified

November 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 04/24

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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