Auto Transplant for High Risk or Relapsed Solid Tumor - Full Text View

Purpose

This is a standard of care treatment guideline for high risk or relapsed solid tumors consisting of a busulfan, melphalan, thiotepa conditioning followed by an autologous peripheral blood stem cell transplant and, if appropriate, disease specific radiation therapy at day +60.

Condition	Intervention
Hematopoietic Stem Cell Transplantation Solid Tumor Transplantation, Autologous	Drug: Ifosfamide Drug: Etoposide phosphate Drug: Mesna Biological: Granulocyte colony-stimulating factor Drug: Busulfan Drug: Melphalan Drug: Thiotepa Biological: Autologous stem cell infusion Radiation: Radiation

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Alkylator-Intense Conditioning Followed by Autologous Transplantation for Patients With High Risk or Relapsed Solid Tumor

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Thiotepa Busulfan Melphalan Melphalan hydrochloride Ifosfamide Mesna Etoposide Etoposide phosphate Filgrastim Sargramostim 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 [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
Number of patients who have received autologous transplant for high risk or relapsed solid tumor and are alive at 1 year.

Secondary Outcome Measures:

Number of Patients Who Achieved Transplant Engraftment [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
Engraftment is defined as absolute neutrophil recovery > 500 cells/ul.
Disease Free Survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
Number of patients who do not have evidence of disease returning after transplant (alive and in remission).
Treatment-Related Mortality [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
Number of patients died due to treatment received.
Disease Free Survival [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
Number of patients who do not have evidence of disease returning after transplant (alive and in remission).

Estimated Enrollment:	20
Study Start Date:	October 2011
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Patients with High Risk or Relapsed Solid Tumor Treatment consists of a mobilization chemotherapy (ifosfamide 1.8 g/m^2/day intravenously [IV], etoposide 100 mg/mg^2 IV, mesna 1.8 g/m^2 divided in every 6 hours dosing, and granulocyte colony stimulating factor 10 mcg/kg subcutaneously or IV until absolute neutrophils > 1,000/mm^2) for 5 days in a 30-100 day pretransplant window, busulfan (1.1 mg/kg IV every 6 hours on days -8 through -6), melphalan (50 mg/mg^2 on days -5 and -4), thiotepa conditioning (250 mg/m^2 IV over 2 hours on days -3 and -2) followed by an autologous peripheral blood stem cell transplant (infusion on Day 0) and, if appropriate, disease specific radiation therapy at day +60.	Drug: Ifosfamide Ifosfamide 1.8 g/m^2/day intravenously (IV) over 1 hour; given in a window of 30-100 days before transplant for 5 days before conditioning regimen Other Names: Mitoxana Ifex Drug: Etoposide phosphate Etoposide 100 mg/m^2/day intravenously (IV) over 1 hour; given in a window of 30-100 days before transplant for 5 days prior to conditioning regimen. Other Names: Eposin Etopophos Vepesid VP-16 Drug: Mesna Mesna 1.8 g/m^2/day divided in every 6 hrs dosing; given in a window of 30-100 days before transplant for 5 days prior to conditioning regimen. Other Names: Uromitexan Mesnex Biological: Granulocyte colony-stimulating factor Beginning 24 hours after treatment with ifosfamide, etoposide and mesna, administer 10 mcg/kg/day subcutaneously (SQ) or intravenously (IV) until absolute neutrophil count (ANC) is greater than (>) 1,000/mm^2. Starting that day, increase dose to 15 mcg/kg/day SQ or IV given as a single injection for 3 doses. All patients should receive G-CSF, 5 ug/kg/day IV as a bolus injection each evening beginning on day 0 until the ANC is >2500 x 10^9/L for 2 consecutive days. G-CSF will subsequently be restarted at 5 ug/kg/day SC or IV if the ANC falls below 1000/mm^3. Other Name: G-CSF Drug: Busulfan Pretransplant conditioning regimen: if <12 kg, 1.1 mg/kg intravenously (IV) every 6 hours,if ≥ 12 kg, 0.8 mg/kg IV every 6 hours on Days 6-8 pretransplant. Other Name: Busulfex Drug: Melphalan Pretransplant conditioning regimen: 50 mg/m^2 intravenously (IV) over 30 min on Days 4 and 5 pretransplant. Other Name: 50 mg/m2 IV over 30 min Drug: Thiotepa Pretransplant conditioning regimen: 250 mg/m^2 intravenously (IV) over 2 hrs on days 2 and 3 before transplant. Other Name: Thioplex Biological: Autologous stem cell infusion On Day 0, stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines. Radiation: Radiation If a patient is considered for post-transplant irradiation, a disease appropriate full tumor restaging should be done prior to starting. Whole lung irradiation (1500cGy in 10 fractions) may be given in patients with prior lung metastasis. Areas of known metastatic disease or PET areas may receive "spot" irradiation using a dose and method determined to be tolerable by radiation oncology staff. Additional radiation will be given if primary disease has not been irradiated to maximum tolerated dose.

Arms

Assigned Interventions

Patients with High Risk or Relapsed Solid Tumor

Treatment consists of a mobilization chemotherapy (ifosfamide 1.8 g/m^2/day intravenously [IV], etoposide 100 mg/mg^2 IV, mesna 1.8 g/m^2 divided in every 6 hours dosing, and granulocyte colony stimulating factor 10 mcg/kg subcutaneously or IV until absolute neutrophils > 1,000/mm^2) for 5 days in a 30-100 day pretransplant window, busulfan (1.1 mg/kg IV every 6 hours on days -8 through -6), melphalan (50 mg/mg^2 on days -5 and -4), thiotepa conditioning (250 mg/m^2 IV over 2 hours on days -3 and -2) followed by an autologous peripheral blood stem cell transplant (infusion on Day 0) and, if appropriate, disease specific radiation therapy at day +60.

Drug: Ifosfamide

Ifosfamide 1.8 g/m^2/day intravenously (IV) over

1 hour; given in a window of 30-100 days before transplant for 5 days before conditioning regimen

Other Names:

Mitoxana
Ifex

Drug: Etoposide phosphate

Etoposide 100 mg/m^2/day intravenously (IV) over 1 hour; given in a window of 30-100 days before transplant for 5 days prior to conditioning regimen.

Other Names:

Eposin
Etopophos
Vepesid
VP-16

Drug: Mesna

Mesna 1.8 g/m^2/day divided in every 6 hrs dosing; given in a window of 30-100 days before transplant for 5 days prior to conditioning regimen.

Other Names:

Uromitexan
Mesnex

Biological: Granulocyte colony-stimulating factor

Beginning 24 hours after treatment with ifosfamide, etoposide and mesna, administer 10 mcg/kg/day subcutaneously (SQ) or intravenously (IV) until absolute neutrophil count (ANC) is greater than (>) 1,000/mm^2. Starting that day, increase dose to 15 mcg/kg/day SQ or IV given as a single injection for 3 doses. All patients should receive G-CSF, 5 ug/kg/day IV as a bolus injection each evening beginning on day 0 until the ANC is >2500 x 10^9/L for 2 consecutive days. G-CSF will subsequently be restarted at 5 ug/kg/day SC or IV if the ANC falls below 1000/mm^3.

Other Name: G-CSF

Drug: Busulfan

Pretransplant conditioning regimen: if <12 kg, 1.1 mg/kg intravenously (IV) every 6 hours,if ≥ 12 kg, 0.8 mg/kg IV every 6 hours on Days 6-8 pretransplant.

Other Name: Busulfex

Drug: Melphalan

Pretransplant conditioning regimen: 50 mg/m^2 intravenously (IV) over 30 min on Days 4 and 5 pretransplant.

Other Name: 50 mg/m2 IV over 30 min

Drug: Thiotepa

Pretransplant conditioning regimen: 250 mg/m^2 intravenously (IV) over 2 hrs on days 2 and 3 before transplant.

Other Name: Thioplex

Biological: Autologous stem cell infusion

On Day 0, stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.

Radiation: Radiation

If a patient is considered for post-transplant irradiation, a disease appropriate full tumor restaging should be done prior to starting. Whole lung irradiation (1500cGy in 10 fractions) may be given in patients with prior lung metastasis. Areas of known metastatic disease or PET areas may receive "spot" irradiation using a dose and method determined to be tolerable by radiation oncology staff. Additional radiation will be given if primary disease has not been irradiated to maximum tolerated dose.

Eligibility

Ages Eligible for Study:	up to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

All patients must have histological verification of malignancy at original diagnosis.

Eligible Diseases
- Ewing's Family Tumors (ES/PNET/DSRCT) - metastatic at time of diagnosis and/or relapsed after therapy
- Renal Tumors - relapsed (all histology - Wilm's tumor) or at diagnosis (clear cell sarcoma and Rhabdoid tumor)
- Hepatoblastoma - metastatic at time of diagnosis and/or relapsed after therapy
- Rhabdomyosarcoma - metastatic at time of diagnosis and/or relapsed after therapy
- Soft Tissue Sarcoma - chemotherapy responsive metastatic disease or chemotherapy responsive relapsed disease
- Primary Malignant Brain Neoplasms <18 years of age - at diagnosis and/or relapse
- Retinoblastoma - disseminated at diagnosis and/or relapsed
- Other High Risk Metastatic or Relapsed Solid Tumors - to be approved by 2 or more pediatric hematology/oncology and bone marrow transplant (BMT) physicians
Disease Status at Enrollment must have fit one of the following:
- no evidence of disease or
- stable, non-progressive disease (defined as non-progressive abnormalities on physical exam or CT and/or MRI) within 4 weeks of study entry
Age and Performance Status
- Age: 0 - 70 years
- Performance status: Karnofsky Performance Status at least 50% for patients > 16 years of age or Lansky Play Score at least 50 for patients less than or equal to 16 years of age. (Note: Neurologic deficits in patients with central nervous system (CNS) tumors must be stable for a minimum of 1 week prior to study entry
Organ Function
- Hematologic: hemoglobin of >9 gm/dl and platelet count > 20,000/μl. Patients may receive transfusions as necessary.
- Renal: Glomerular Filtration Rate (GFR) ≥ 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x upper limit of normal (ULN) for age
- Hepatic: aspartate aminotransferase or alanine aminotransferase (AST or ALT) ≤ 5 x ULN and bilirubin ≤ 5 x ULN
- Cardiac: ejection fraction ≥ 45% or no clinical evidence of heart failure
- Pulmonary: oxygen saturation > 92% at rest (on room air)

Exclusion Criteria:

Pregnant or breastfeeding
Active, uncontrolled infection and/or human immunodeficiency virus (HIV) positive

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01505569

Contacts

Contact: Patricia Kleinke, RN

612-273-2800

pkleink1@fairview.org

Locations

United States, Minnesota
Masonic Cancer Center, University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Michael Verneris, M.D. 612-626-2961 verneris@umn.edu
Contact: Patricia Kleinke, RN 612-273-2800 pkleink1@fairview.org
Principal Investigator: Michael Verneris, M.D.

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Michael Verneris, M.D.

Masonic Cancer Center, University of Minnesota

More Information

No publications provided

Responsible Party:	Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT01505569 History of Changes
Other Study ID Numbers:	2011OC057, MT2011-09C
Study First Received:	January 4, 2012
Last Updated:	November 13, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:

autologous transplantation
high risk solid tumor
relapsed solid tumor

Additional relevant MeSH terms:

Neoplasms
Mesna
Busulfan
Melphalan
Thiotepa
Ifosfamide
Isophosphamide mustard
Etoposide phosphate
Etoposide
Lenograstim
Protective Agents
Physiological Effects of Drugs

Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on May 23, 2013