Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors
Condition: Childhood Germ Cell Tumor; Ovarian Cancer; Teratoma
MeSH terms: Neoplasms, Germ Cell and Embryonal; Teratoma
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Germ cell tumors (GCT) are highly sensitive to chemotherapy such that even with
      metastatic disease at diagnosis, many patients can be cured. Patients who fall into the poor
      risk category or others who relapse can be successfully salvaged with high dose chemotherapy
      and autologous stem cell transplant (AuSCT). As in other diseases such as myeloma, sequential
      high dose chemotherapy and AuSCT may improve overall and disease free survival.

      PURPOSE: Because prior investigations in GCT suggest that a subset of high risk or relapsed
      patients may be cured with sequential cycles of high dose chemotherapy and AuSCT, we propose
      investigating how well non-cross resistant conditioning regimens work in treating patients
      with relapsed or high risk GCT.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine overall survival (OS) of patients with germ cell tumors treated with tandem
           autologous stem cell transplantation with non-cross-resistant conditioning regimens.

      Secondary

        -  Determine disease-free survival (DFS) of patients treated with this regimen.

        -  Determine the toxicity of tandem transplants

        -  Determine the time to engraftment of neutrophils and platelets in patients treated for
           each transplant

        -  Determine the number of patients unable to adequately mobilize sufficient peripheral
           blood stem cells (PBSC) for tandem transplantation.

        -  Identify prognostic factors of patients unlikely to mobilize sufficient PBSC for tandem
           transplantation.

        -  Compare OS and DFS of patients undergoing single vs tandem transplantation.

      OUTLINE:

        -  Peripheral blood stem cell (PBSC) mobilization with filgrastim (G-CSF): Patients receive
           G-CSF subcutaneously (SC) beginning on day 1 and continuing until stem cell collection
           is complete. Patients undergo stem cell collection beginning on day 5 of G-CSF
           administration and continuing for at least 3 collections until the collection goal is
           met.

        -  Second PBSC mobilization with chemotherapy: Patients not meeting the collection goal
           receive cyclophosphamide IV over 2 hours on day 1 and G-CSF SC beginning on day 4 and
           continuing until stem cell collection is complete. Patients meeting the collection goal
           after PBSC mobilization via G-CSF alone or in combination with chemotherapy will undergo
           tandem autologous transplantation. If collection goal is not met but the patient has
           collected > or = 2 x 10^6 CD34 cells/kg, a single autologous transplant will be
           performed.

        -  Single stem cell transplantation (SCT): Patients receive paclitaxel IV over 3 hours on
           day -7 and ifosfamide IV on days -6 to -4. Patients undergo reinfusion of stem cells on
           day 0. Patients also receive G-CSF SC or IV beginning on day 1 and continuing until
           blood counts recover.

        -  Tandem SCT: Patients receive treatment as in single SCT. Beginning 30-90 days later,
           patients receive carboplatin IV over 60 minutes and thiotepa IV over 30 minutes on days
           -6 to -4 and etoposide IV over 60 minutes on days -6 to -3. Patients undergo reinfusion
           of stem cells on day 0. Patients also receive G-CSF SC or IV beginning on day 5 and
           continuing until blood counts recover.

      After completion of study treatment, patients are followed at 6, 9, and 12 months and then
      every 6 months for up to 2 years.

      PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.
    

Intervention name(s): carboplatin; etoposide; ifosfamide; paclitaxel; thiotepa; autologous hematopoietic stem cell transplantation; Mesna; filgrastim
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Procedure; Drug; Biological
Intervention description(s): Days -6, -5, -4: 500mg/m2^/day intravenously (IV) over 60 minutes; 600mg/m^2/day intravenously (IV) over 60 minutes on Days -6 through -3.; 2500 mg/m^2/day continuous infusion intravenously on Days -6, -5 and -4.; 225 mg/m^2 intravenous over 3 hours on Day -7.; 150mg/m^2/day intravenously IV over 30 minutes; Days -6, -5 and -4; Peripheral blood stem cell infusion (< 4 x 10^6 CD34+ cells/kg); 2500 mg/m^2/day continuous infusion intravenously on Days -6, -5 and -4.; Beginning Day 5, G-CSF 5 μg/kg/day until absolute neutrophil count (ANC) ≥ 1500/UL for 3 consecutive days.
Other intervention name(s): VP-16; Toposar; Mitoxana; Ifex; Taxol; N,N'N'-triethylenethiophosphoramide; PBSC; Uromitexan®; G-CSF
Intervention MeSH terms: Paclitaxel; Etoposide; Carboplatin; Ifosfamide; Thiotepa; Mesna
Intervention model: Single Group Assignment
Intervention model description: This trial is single arm study and it is non-randomized. Overall, if patients did not have enough cells to do two transplants then they only received one transplants.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: childhood extragonadal germ cell tumor; childhood malignant ovarian germ cell tumor; childhood malignant testicular germ cell tumor; stage III malignant testicular germ cell tumor; testicular choriocarcinoma and seminoma; testicular embryonal carcinoma and seminoma; testicular embryonal carcinoma and teratoma with seminoma; testicular embryonal carcinoma and yolk sac tumor with seminoma; testicular yolk sac tumor and teratoma with seminoma; testicular choriocarcinoma and embryonal carcinoma; testicular choriocarcinoma and teratoma; testicular choriocarcinoma and yolk sac tumor; testicular choriocarcinoma; testicular embryonal carcinoma and teratoma; testicular embryonal carcinoma and yolk sac tumor; testicular embryonal carcinoma; testicular yolk sac tumor and teratoma; testicular yolk sac tumor; testicular seminoma; stage IV extragonadal non-seminomatous germ cell tumor; stage IV extragonadal seminoma; stage I extragonadal non-seminomatous germ cell tumor; stage I extragonadal seminoma; stage II extragonadal non-seminomatous germ cell tumor; stage II extragonadal seminoma; stage III extragonadal non-seminomatous germ cell tumor; stage III extragonadal seminoma; stage II ovarian germ cell tumor; stage I malignant testicular germ cell tumor; stage II malignant testicular germ cell tumor; adult teratoma; childhood teratoma; testicular immature teratoma; testicular mature teratoma; adult central nervous system germ cell tumor; childhood central nervous system germ cell tumor