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
18 Years
65 Years
Both
Malignant Lymphoma
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Outcome Measure:
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.
Outcome Time Frame:
From inclusion to 1 months post transplantation
Safety Issue:
Yes
Principal Investigator
Hans E Johnsen, MD DMSc
Investigator Role:
Principal Investigator
Investigator Affiliation:
Aalborg Hospital and Herlev University Hospital
Authority:
Denmark: Danish Dataprotection Agency
Study ID:
SCF 980266
NCT ID:
NCT01016795
Start Date:
January 1999
Completion Date:
November 2009
Related Keywords:
- Malignant Lymphoma
- SCF
- Priming
- Mobilization
- Lymphoma
- Clinical Trial
- Lymphoma
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