Randomized Trial of G-CSF Alone Versus Intermediate-dose Ara-C Plus G-CSF Mobilization in Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma

Maria Sklodowska-Curie National Research Institute of Oncology

Status and phase: Unknown; Phase 3

Conditions: Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma

Treatments: Drug: Cytosine arabinoside with G-CSF (filgrastim); Drug: G-CSF (filgrastim)

Study type: Interventional

Funder types: Other

Identifiers

NCT02722733

HL/NHLMobil-COI-01

Details and patient eligibility

About

The purpose of the study is to compare safety and efficacy of stem cell mobilization using G-CSF (filgrastim) alone vs. intermediate-dose cytosine arabinoside plus G-CSF in Hodgkin's lymphoma and non-Hodgkin's lymphoma patients.

Full description

Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard treatment of eligible patients suffering from Hodgkin's Lymphoma or non-Hodgkin's Lymphoma (HL, NHL). AutoHSCT allows to further improve results of the therapy. Nowadays, 99% of the procedures are performed using peripheral blood as a source of stem cells. Hence, the crucial point is to harvest adequate number of stem cells allowing hematopoietic recovery. The number of 2 × 10^6 CD34+ cells/kg is considered the minimal level in autoHSCT. There are two main mobilization strategies being used: based on G-CSF alone or in combination with chemotherapy (cyclophosphamide (CY) at dose range 1.6 g/m2 is mainly used in HL and NHL setting). However, a proportion of patients (5-40%) fail to collect the minimum number of cells required. Novel agents, like plerixafor, CXCR4 inhibitor, may enable effective CD34+ cell harvest in "poor mobilizers". Nevertheless, the optimal first-line and cost-effective protocol for mobilization of hematopoietic stem cells has not been determined so far.

Randomized trials compare chemomobilization with the use of CY + G-CSF to G-CSF alone, which had been conducted so far, did not demonstrate clear advantage of addition of CY to the growth factor. Intermediate-dose cytosine arabinoside (AraC), 1.6 g/m2 plus filgrastim, has been shown to produce very high efficacy as a first or second-line mobilization regimen in patients with lymphoid malignancies. In a retrospective comparison, this strategy was significantly more effective than CY + G-CSF. This suggest that the type of chemotherapy agent added to G-CSF may play role in mobilization efficacy and that the combination of AraC and G-CSF may be more effective than G-CSF used alone. The goal of current study is to verify this hypothesis in randomized controlled trial.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Hodgkin's lymphoma and non-Hodgkin's lymphoma patients considered eligible for autologous stem cell transplantation procedure.
2. Must not have achieved complete remission after first line of therapy or must have relapsed lymphoma.
3. Must have received at least two lines of therapy including four or more cycles.
4. Must have achieved a partial (PR) or complete remission (CR) .
5. Must be 18-65 years of age.
6. Must have World Health Organization performance status 0-1.
7. Time from administration or discontinuation of any chemotherapy agent must be at least four weeks.
8. Hemoglobin level > 8 g/dl, Absolute neutrophil count (ANC) > 1.5 x 10^9/L, Platelet count >100 x 10^9/L.
9. Serum creatinine < 1.5 x upper limit of normal (ULN), serum bilirubin < 1.5 ULN, serum aspartate transaminase (AST/SGOT) < 2.5 x ULN, serum alanine transaminase (ALT/SGPT) < 2.5 x ULN.
10. Negative human immunodeficiency virus (HIV) infection test.
11. Negative pregnancy test.
12. Must understand and voluntarily sign informed consent form.

Exclusion criteria

1. Failure of prior, first-line mobilization regimen.
2. Infiltration of central nervous system.
3. Bone marrow plasma cell infiltration of above 20%.
4. Administration of nitrosourea derivatives (Carmustine, Lomustine) within 4 weeks before starting study treatment.
5. Administration of growth-factor other than G-CSF Administration of G-CSF within 14 days before starting study treatment.
6. Ongoing or active infection.
7. Coexisting neoplasm, other than Hodgkin's or non-Hodgkin's lymphoma.
8. Administration of radioimmunotherapy in past.
9. Pregnant or lactating females.
10. Patients treated with use of autologous or allogenic stem cell transplantation in the past.
11. Positive human immunodeficiency virus (HIV) infection test.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

G-CSF (filgrastim)

Active Comparator group

Description:

1.G-CSF at 10 μg/kg per day (divided into two doses every 12 hours) subcutaneously for up to 7 days.

Treatment:

Drug: G-CSF (filgrastim)

Cytosine arabinoside + G-CSF (filgrastim)

Active Comparator group

Description:

Cytosine arabinoside will be administered as a 2-hour i.v. infusion at a dose of 0.4 g/m2 twice daily on days 1 and 2 (total dose 1.6 g/m2). G-CSF 5-10 μg/kg per day (divided into two doses every 12 hours) will be started on day 5 subcutaneously and continued until last leukapheresis.

Treatment:

Drug: Cytosine arabinoside with G-CSF (filgrastim)