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

NCT ID: NCT01016795

Last Updated: 2015-06-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-01-31
• Study Completion Date: 2009-11-30

Brief Summary

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.

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.

Conditions

Malignant Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

r-metHuSCF and Filgrastim

Intervention Type: DRUG

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.

r-metHuSCF and Filgrastim

Intervention Type: DRUG

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.

Chemotherapy plus Filgrastim

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

r-metHuSCF and Filgrastim

Intervention Type: DRUG

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.

Chemotherapy plus Filgrastim

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Stem Cell Factor and G-CSF; Stem Cell Factor and G-CSF; Priming chemotherapy and G-CSF

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Herlev Hospital

OTHER

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: collaborator

Helsinki University Central Hospital

OTHER

Sponsor Role: collaborator

Turku University Hospital

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Linkoeping

OTHER

Sponsor Role: collaborator

Umeå University

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: collaborator

Nordic Lymphoma Group

NETWORK

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: collaborator

Aalborg University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Department of Haematology Aalborg Hospital Denmark

Principal Investigators

Hans E Johnsen, MD DMSc

Role: PRINCIPAL_INVESTIGATOR

Aalborg Hospital and Herlev University Hospital

Locations

Aalborg Hospital

Aalborg, , Denmark

Rigshospitalet

Copenhagen, , Denmark

Herlev University Hospital

Copenhagen, , Denmark

University Hospital Helsinki

Helsinki, , Finland

University Hospital Turku

Turku, , Finland

Radiumhospitalet

Oslo, , Norway

University Hospital Linköping

Linköping, , Sweden

University Hospital Umeå

Umeå, , Sweden

Countries

Denmark; Finland; Norway; Sweden

Other Identifiers

H-KA-99040-GMS

Identifier Type: OTHER

Identifier Source: secondary_id

SCF 980266

Identifier Type: -

Identifier Source: org_study_id