Stem Cell Factor (SCF) Priming of Haematopoietic Stem Cell Grafts in Malignant Lymphoma (SCF980266)

June 24, 2015 updated by: Aalborg University Hospital

A Randomized Study of Peripheral Blood Progenitor Cell Priming Comparing a Combination of r-metHuSCF and Filgrastim or Chemotherapy and Filgrastim on Mobilization and Engraftment in Patients With Relapsed or Refractory Lymphomas

Clinical Hypothesis:

It is expected that by removing chemotherapy and adding ancestim to the mobilization scheme in most of the subjects sufficient PBPC will be harvested with a minimum of toxicity and side effects.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Autologous stem cell transplantation is used to support high dose chemotherapy in haematological malignancies.1-2 Peripheral blood progenitor cells (PBPC) have replaced bone marrow cells as the preferred source for transplantation due to faster blood cell recovery.3-4 One variable of major impact for posttransplant care is the number of PBPC harvested.5-8 Therefore, several clinical studies have aimed to identify priming regimens that improve progenitor and stem cell mobilizations and collections without increased toxicity. Frequently, Filgrastim (r-met HuG-CSF) is administrated alone; however, Filgrastim combined with chemotherapy has proven more effective in context of CD34+ cell numbers harvested9-11 and this combination is considered the gold standard for priming and stem cell mobilization in relapsed malignant lymphoma.

Stem cell factor (SCF) is a glycoprotein growth factor that acts on haematopoietic blood cell progenitors.12 Whereas SCF alone exerts little colony-stimulating activity on normal human bone marrow cells in vitro, combination of SCF with other recombinant haematopoietic cytokines results in a synergistic increase in numbers of colonies.13 In vivo, the addition of SCF to G-CSF (Filgrastim) synergistically increases PBPC mobilization compared to Filgrastim alone.14-17 Several clinical trials have reported the ability of the combination of SCF with Filgrastim to mobilize PBPC in patients with lymphoma, multiple myeloma, breast and ovarian cancers even in heavily pretreated patients.18-26 Priming using chemotherapy is toxic and costly11 and new priming procedures need to be established, which is the background for this randomized pilot study. The hypothesis is that elimination of chemotherapy from the priming regimen may decrease the overall toxicity and the ability to collect a sufficient autograft which, however, may be circumvented by adding r-metHuSCF (Ancestim) to the priming regimen. The aim of this randomized phase II trial was to evaluate safety, toxicity and efficacy of growth factors in lymphoma patients considered candidates for high dose chemotherapy.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2

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

  • Denmark
      • Aalborg, Denmark, 9000
        • Aalborg Hospital
      • Copenhagen, Denmark, 2100
        • Rigshospitalet
      • Copenhagen, Denmark
        • Herlev University Hospital
  • Finland
      • Helsinki, Finland
        • University Hospital Helsinki
      • Turku, Finland
        • University Hospital Turku
  • Norway
      • Oslo, Norway
        • Radiumhospitalet
  • Sweden
      • Linköping, Sweden
        • University Hospital Linköping
      • Umeå, Sweden
        • University Hospital Umeå

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects with Hodgkin's disease and non-Hodgkin lymphomas (Real classification)

    • in relapse
    • refractory to initial chemotherapy
    • with partial response after initial therapy
  • Age > 18 years and < 65 years
  • ECOG performance status 0, 1 or 2
  • Life expectancy of > 6 months with treatment
  • ANC > or equal to 1.5 x 109/L, Platelets > or equal to 100 x 109/L
  • Serum creatinine < or equal to 150 µmol/L, bilirubin, aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT) less than twice the upper limit defined at the investigating laboratory
  • Prior to mobilization chemotherapy subject has given written informed consent, personally dated

Exclusion Criteria:

  • Prior DexaBEAM or miniBEAM therapy and prior bone marrow or PBPC transplant
  • Any history of seasonal or recurrent asthma within the preceding 10 years.
  • Any history of anaphylactic / anaphylactoid-type event manifested by disseminated urticaria, laryngeal oedema, and / or bronchospasm (example, food, insect bites, etc.). Subjects with drug allergies, manifested solely by rash and / or urticaria, are not excluded
  • Any history of angioedema or recurrent urticaria
  • Clinical or microbiological evidence of infection at the date of enrollment.
  • Subjects with a concurrent malignancy
  • Significant non-malignant disease including documented HIV infection, uncontrolled hypertension, unstable angina, congestive heart failure, poorly controlled diabetes, coronary angioplasty within six months, myocardial infarction within the last six months, or uncontrolled atrial or ventricular cardiac arrhythmias
  • Pregnant or breast feeding subjects or those of child-bearing potential who are not using adequate contraceptive precautions
  • Concurrent enrollment on any other protocol using an investigational drug
  • Haematopoietic growth factors administered within one week of study entry
  • Subjects with a psychiatric, addictive or any disorder which compromises ability to give truly informed consent for participation in this study
  • Known sensitivity to E. coli derived products
  • Concurrent use of beta adrenergic blocking agents

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: r-metHuSCF and Filgrastim
Patients were randomized in a 1:1 ratio to either chemotherapy combined with 10 µg/kg/d Filgrastim (control arm B), administered by subcutaneous injection for 14 days, or the combination of 10 µg/kg/d Filgrastim and SCF administered subcutaneously at a dose of 20 µg/kg/d (experimental arm A) for 8 days. Different injection sites were used for each cytokine.
Drug: r-metHuSCF and Filgrastim
Patients were randomized in a 1:1 ratio to either chemotherapy combined with 10 µg/kg/d Filgrastim (control arm B), administered by subcutaneous injection for 14 days, or the combination of 10 µg/kg/d Filgrastim and SCF administered subcutaneously at a dose of 20 µg/kg/d (experimental arm A) for 8 days. Different injection sites were used for each cytokine.
Other Names:
  • Stem Cell Factor and G-CSF
Drug: Chemotherapy plus Filgrastim
Patients were randomized in a 1:1 ratio to either chemotherapy combined with 10 µg/kg/d Filgrastim (control arm B), administered by subcutaneous injection for 14 days, or the combination of 10 µg/kg/d Filgrastim and SCF administered subcutaneously at a dose of 20 µg/kg/d (experimental arm A) for 8 days. Different injection sites were used for each cytokine.
Other Names:
  • Priming chemotherapy and G-CSF
Active Comparator: Cyclophosphamide and Filgrastim
Patients were randomized in a 1:1 ratio to either chemotherapy combined with 10 µg/kg/d Filgrastim (control arm B), administered by subcutaneous injection for 14 days, or the combination of 10 µg/kg/d Filgrastim and SCF administered subcutaneously at a dose of 20 µg/kg/d (experimental arm A) for 8 days. Different injection sites were used for each cytokine.
Drug: r-metHuSCF and Filgrastim
Patients were randomized in a 1:1 ratio to either chemotherapy combined with 10 µg/kg/d Filgrastim (control arm B), administered by subcutaneous injection for 14 days, or the combination of 10 µg/kg/d Filgrastim and SCF administered subcutaneously at a dose of 20 µg/kg/d (experimental arm A) for 8 days. Different injection sites were used for each cytokine.
Other Names:
  • Stem Cell Factor and G-CSF
Drug: Chemotherapy plus Filgrastim
Patients were randomized in a 1:1 ratio to either chemotherapy combined with 10 µg/kg/d Filgrastim (control arm B), administered by subcutaneous injection for 14 days, or the combination of 10 µg/kg/d Filgrastim and SCF administered subcutaneously at a dose of 20 µg/kg/d (experimental arm A) for 8 days. Different injection sites were used for each cytokine.
Other Names:
  • Priming chemotherapy and G-CSF

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety and Toxicity was assessed by morbidity, including unexpected adverse events associated with the priming and the transplantation phases during study, and measured and graded by CTC criteria.
Time Frame: From inclusion to 1 months post transplantation
From inclusion to 1 months post transplantation

Secondary Outcome Measures

Outcome Measure
Time Frame
To compare the time dependent level of blood circulating and harvested haematopoietic stem cells and progenitors (PBSC) in patients treated with either a combination of r-metHuSCF and Filgrastim, or conventional chemotherapy plus Filgrastim.
Time Frame: From inclusion to 1 months post transplantation
From inclusion to 1 months post transplantation

Collaborators and Investigators

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

Sponsor

Aalborg University Hospital

Collaborators

Turku University Hospital
Oslo University Hospital
Helsinki University Central Hospital
Rigshospitalet, Denmark
Umeå University
Amgen
Herlev Hospital
University Hospital, Linkoeping
Nordic Lymphoma Group

Investigators

  • Principal Investigator: Hans E Johnsen, MD DMSc, Aalborg Hospital and Herlev University Hospital

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

January 1, 1999

Primary Completion (Actual)

November 1, 2000

Study Completion (Actual)

November 1, 2009

Study Registration Dates

First Submitted

November 18, 2009

First Submitted That Met QC Criteria

November 19, 2009

First Posted (Estimate)

November 20, 2009

Study Record Updates

Last Update Posted (Estimate)

June 25, 2015

Last Update Submitted That Met QC Criteria

June 24, 2015

Last Verified

November 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCF 980266
  • H-KA-99040-GMS (Other Identifier: The Danish National Committee on Biomedical Research Ethics)

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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