Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors

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.

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.