Clinical trial NCT00432094: Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors
Official title: Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Childhood Germ Cell Tumor
Ovarian Cancer
Teratoma
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
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2007-02-07
Enrollment: 23
Sex: ALL
Minimum age (years): 10
Maximum age (years): 69
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

Brief 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.

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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 1 Year
Secondary outcomes:
measure: Disease-free Survival (DFS)
timeFrame: 1 Year
measure: Engraftment of Platelets
timeFrame: Day 100
measure: Numbers of Patients Unable to Mobilize Peripheral Blood Stem Cells
timeFrame: Pre-Transplant
measure: Engraftment of Neutrophils
timeFrame: Day 42
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Najla El Jurdi, MD
role: PRINCIPAL_INVESTIGATOR
References: