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

This study has been completed.
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by:
Peter MacCallum Cancer Centre, Australia
ClinicalTrials.gov Identifier:
NCT00400556
First received: November 15, 2006
Last updated: NA
Last verified: November 2006
History: No changes posted
  Purpose

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

Condition Intervention Phase
Multiple Myeloma
Cutaneous Lymphoma
Drug: ATRA plus G-CSF (filgrastim, NEUPOGEN (R)) combination
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Haematopoietic Stem Cell Mobilization Using G-CSF With ATRA in Patients With Cutaneous Lymphoma and Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Peter MacCallum Cancer Centre, Australia:

Primary Outcome Measures:
  • 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

Estimated Enrollment: 6
Study Start Date: March 2005
Estimated Study Completion Date: May 2005
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00400556

Locations
Australia, Victoria
Peter MacCallum Cancer Center
East Melbourne, Victoria, Australia, 3002
Sponsors and Collaborators
Peter MacCallum Cancer Centre, Australia
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
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00400556     History of Changes
Other Study ID Numbers: 04/24
Study First Received: November 15, 2006
Last Updated: November 15, 2006
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Peter MacCallum Cancer Centre, Australia:
mobilization
ATRA
G-CSF
filgrastim
retinoids
stem cell mobilization
hematopoietic stem and progenitor cells

Additional relevant MeSH terms:
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014