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
Intervention: carboplatin; etoposide; ifosfamide; paclitaxel; thiotepa; autologous hematopoietic stem cell transplantation; Mesna; filgrastim
Intervention description: 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.
Intervention MeSH terms: Paclitaxel; Etoposide; Carboplatin; Ifosfamide; Thiotepa; Mesna
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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)
Enrollment: 23.0
Sex: All
Minimum age: 10 Years
Maximum age: 69 Years
Healthy volunteers: No
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

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis: Poor Prognosis Non-Seminomas Germ Cell Tumor in ≥ PR1/CR1 or Good or
             Intermediate Prognosis Seminomas and Non- Seminomas Germ Cell Tumor in ≥ PR1 or ≥ CR2
             as defined by the International Germ Cell Cancer Consensus Classification. Patients
             with increasing tumor markers only (i.e. no imaging evidence of progressive disease)
             are eligible for transplant.

          -  Age: ≥ 10 years and < 70 years of age.

          -  Performance status: Karnofsky ≥ 80% (subjects ≥ 16 years of age) Lansky ≥ 80% for
             subject 10 - 15 years of age

          -  Life expectancy: Greater than 8 weeks.

          -  Patients must have normal organ function as defined below:

               -  Hematologic:

                    -  Hemoglobin > 8 gm/dL without transfusion and off erythropoietin for 14 days
                       or Aranesp for 21 days

                    -  White blood cells (WBC) > 2.5 x 10^9/L with an absolute neutrophile count
                       (ANC) > 1.5 x 10^9/L and off G-CSF or GM-CSF for 10 days or Neulasta for 21
                       days

                    -  Platelets > 100 x 10^9/L without transfusion and/or a bone marrow
                       cellularity of ≥ 20%

               -  Renal: Creatinine ≤ 2.0 mg/dl or creatinine clearance > 50 ml/min.

               -  Hepatic: Total bilirubin ≤ 2.0 mg/dl, AST and alkaline phosphatase < 5 x upper
                  limit of normal. No history of severe prior or ongoing chronic liver disease.

               -  Cardiac: Patients must be free of symptoms of uncontrolled cardiac disease
                  including unstable angina, decompensated congestive heart failure, or arrhythmia.
                  LVEF ≥45% by MUGA/ECHO.

               -  Pulmonary: Patients must have no significant obstructive airways disease (FEV1
                  must be ≥ 50% of predicted) and must have acceptable diffusion capacity
                  (corrected DLCO > 50% of predicted).

          -  Patients with a history of CNS tumor involvement are eligible if they have completed
             treatment for CNS disease (radiotherapy or surgery or chemotherapy), have recovered
             from or stabilization of the side effects associated with the therapy and have no
             evidence of progressive CNS disease at the time of enrollment.

        Exclusion Criteria:

          -  Patients with serious uncontrolled infections will not be eligible.

          -  Male and female patients of reproductive potential must use an approved contraceptive
             method if appropriate (for example, intrauterine device [IUD], birth control pills, or
             barrier device) during and for the duration of study participation. The drugs used in
             this study are pregnancy category D - clear evidence of risk in pregnancy.

          -  Pregnant and breast feeding women will not be eligible.

        Voluntary written informed consent before performance of any study-related procedure not
        part of normal medical care, with the understanding that consent may be withdrawn by the
        subject at any time without prejudice to future medical care.

        Additional Eligibility prior to Transplant Two:

          -  Total Collection of ≥ 4 x 10^6 CD34 cells/kg prior to transplant one

          -  Transplant able to occur between day +30 and day +90 from transplant one

          -  Recovery of blood counts as demonstrated by:

               -  WBC > 2.5 x 10^9/L with an ANC > 1.5 x 10^9/L and off G-CSF for 3 days

               -  Platelets > 50 x 10^9/L without transfusion in the prior 7 days

               -  Renal: Creatinine ≤ 2.0 mg/dl or creatinine clearance > 50 ml/min

               -  Hepatic: Total bilirubin ≤ 2.0 mg/dl, AST and alkaline phosphatase < 5 x upper
                  limit of normal

          -  Infection: Patients with serious uncontrolled infections at the time of planned
             transplant will be excluded

          -  Patients with progressive disease by Response Evaluation Criteria in Solid Tumors
             (RECIST) criteria by imaging techniques are not eligible to proceed to the second
             transplant. Tumor marker increase alone is not sufficient to diagnose disease
             progression.