Stem Cell Factor (SCF) Priming of Haematopoietic Stem Cell Grafts in Malignant Lymphoma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Malignant Lymphoma	Drug: r-metHuSCF and Filgrastim Drug: Chemotherapy plus Filgrastim	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Filgrastim Lenograstim Granulocyte colony-stimulating factor

U.S. FDA Resources

Further study details as provided by Aalborg Universityhospital:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Enrollment:	32
Study Start Date:	January 1999
Estimated Study Completion Date:	November 2009
Estimated Primary Completion Date:	November 2000 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: Stem Cell Factor and G-CSF 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 Name: 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 Name: 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 Name: 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 Name: Priming chemotherapy and G-CSF

Arms

Assigned Interventions

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 Name: Stem Cell Factor and G-CSF

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 Name: 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 Name: 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 Name: 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 Name: Priming chemotherapy and G-CSF

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01016795

Locations

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

Sponsors and Collaborators

Aalborg Universityhospital

Herlev Hospital

Rigshospitalet, Denmark

Helsinki University Central Hospital

Turku University Hospital

University Hospital, Linkoeping

Umeå University

Radiumhospitalet Oslo Norway

Nordic Lymphoma Group

Amgen

Investigators

Principal Investigator:

Hans E Johnsen, MD DMSc

Aalborg Hospital and Herlev University Hospital

More Information

No publications provided

Responsible Party:	Hans Erik Johnsen MD DMSc, Professor Clinical Haematology, Department of Haematology Aalborg Hospital Denmark
ClinicalTrials.gov Identifier:	NCT01016795 History of Changes
Other Study ID Numbers:	SCF 980266, H-KA-99040-GMS
Study First Received:	November 18, 2009
Last Updated:	November 19, 2009
Health Authority:	Denmark: Danish Dataprotection Agency Denmark: Danish Medicines Agency Denmark: The Danish National Committee on Biomedical Research Ethics Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by Aalborg Universityhospital:

SCF
Priming
Mobilization
Lymphoma
Clinical Trial

Additional relevant MeSH terms:

Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders

Immune System Diseases
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013

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