Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors
This study is currently recruiting participants.
Verified February 2013 by Masonic Cancer Center, University of Minnesota
Sponsor:
Masonic Cancer Center, University of Minnesota
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00432094
First received: February 5, 2007
Last updated: February 14, 2013
Last verified: February 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Childhood Germ Cell Tumor Ovarian Cancer Teratoma |
Drug: carboplatin Drug: etoposide Drug: ifosfamide Drug: paclitaxel Drug: thiotepa Procedure: autologous hematopoietic stem cell transplantation Drug: Mesna Biological: filgrastim |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors |
Resource links provided by NLM:
Drug Information available for:
Thiotepa
Ifosfamide
Mesna
Paclitaxel
Etoposide
Carboplatin
Etoposide phosphate
Filgrastim
Lenograstim
Granulocyte colony-stimulating factor
U.S. FDA Resources
Further study details as provided by Masonic Cancer Center, University of Minnesota:
Primary Outcome Measures:
- Overall survival (OS) [ Time Frame: 1 Year ] [ Designated as safety issue: No ]The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate.
Secondary Outcome Measures:
- Disease-free survival (DFS) [ Time Frame: 1 Year ] [ Designated as safety issue: No ]The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.
- Engraftment of platelets [ Time Frame: Day 42 and Day 100 ] [ Designated as safety issue: No ]Platelet engraftment is defined as 20,000/mm^3 (20 x 10^9/L) for 3 consecutive days unsupported by a platelet transfusion.
- Numbers of Patients Unable to Mobilize Peripheral Blood Stem Cells [ Time Frame: Pre-Transplant ] [ Designated as safety issue: No ]Number of patients unable to achieve adequate stem cell mobilization, need to undergo one or tandem transplantation. Stem cell mobilization = A process in which certain drugs are used to cause the movement of stem cells from the bone marrow into the blood. The stem cells can be collected and stored. They may be used later to replace the bone marrow during a stem cell transplant.
- Engraftment of neutrophils [ Time Frame: Day 42 and Day 100 ] [ Designated as safety issue: No ]Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 109/L) or greater.
| Estimated Enrollment: | 25 |
| Study Start Date: | December 2006 |
| Estimated Study Completion Date: | June 2014 |
| Estimated Primary Completion Date: | June 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 2 Transplants
Patients with Germ Cell Tumors (GCT) treated with a second tandem autologous stem cell transplant (AuSCT) with non-cross-resistant conditioning regimens.
|
Drug: carboplatin
Days -6, -5, -4: 500mg/m2^/day intravenously (IV) over 60 minutes
Drug: etoposide
600mg/m^2/day intravenously (IV) over 60 minutes on Days -6 through -3.
Other Names:
Drug: thiotepa
150mg/m^2/day intravenously IV over 30 minutes; Days -6, -5 and -4
Other Name: N,N'N'-triethylenethiophosphoramide
Procedure: autologous hematopoietic stem cell transplantation
Peripheral blood stem cell infusion (< 4 x 10^6 CD34+ cells/kg)
Other Name: PBSC
Biological: filgrastim
Beginning Day 5, G-CSF 5 μg/kg/day until absolute neutrophil count (ANC) ≥ 1500/UL for 3 consecutive days.
Other Name: G-CSF
|
|
Active Comparator: 1 Transplant
Patients with Germ cell tumors who receive one transplant only.
|
Drug: ifosfamide
2500 mg/m^2/day continuous infusion intravenously on Days -6, -5 and -4.
Other Names:
Drug: paclitaxel
225 mg/m^2 intravenous over 3 hours on Day -7.
Other Name: Taxol
Procedure: autologous hematopoietic stem cell transplantation
Peripheral blood stem cell infusion (< 4 x 10^6 CD34+ cells/kg)
Other Name: PBSC
Drug: Mesna
2500 mg/m^2/day continuous infusion intravenously on Days -6, -5 and -4.
Other Name: Uromitexan®
Biological: filgrastim
Beginning Day 5, G-CSF 5 μg/kg/day until absolute neutrophil count (ANC) ≥ 1500/UL for 3 consecutive days.
Other Name: G-CSF
|
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| Ages Eligible for Study: | 10 Years to 69 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00432094
Contacts
| Contact: Timothy Krepski | 612-273-2800 | tkrepsk1@fairview.org |
Locations
| United States, Minnesota | |
| Masonic Cancer Center at University of Minnesota | Recruiting |
| Minneapolis, Minnesota, United States, 55455 | |
| Contact: Brian McClune, DO 612-273-2800 bmcclune@umn.edu | |
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
| Principal Investigator: | Brian McClune, DO | Masonic Cancer Center, University of Minnesota |
More Information
Additional Information:
No publications provided
| Responsible Party: | Masonic Cancer Center, University of Minnesota |
| ClinicalTrials.gov Identifier: | NCT00432094 History of Changes |
| Other Study ID Numbers: | 2006LS032, UMN-MT2005-21, UMN-0608M90586 |
| Study First Received: | February 5, 2007 |
| Last Updated: | February 14, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Masonic Cancer Center, University of Minnesota:
|
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 |
Additional relevant MeSH terms:
|
Ovarian Neoplasms Teratoma Neoplasms, Germ Cell and Embryonal Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders Neoplasms by Histologic Type Etoposide |
Paclitaxel Isophosphamide mustard Ifosfamide Thiotepa Carboplatin Lenograstim Antineoplastic Agents, Phytogenic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Immunosuppressive Agents |
ClinicalTrials.gov processed this record on May 23, 2013