Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

NCT01505569 | Completed

• 2 other identifiers: 2011OC057MT2011-09C
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This is a standard of care treatment guideline for high risk or relapsed solid tumors or CNS tumors consisting of a busulfan, melphalan, thiotepa conditioning (for solid tumors) or carboplatin and thiotepa conditioning (for CNS tumors) followed by an autologous peripheral blood stem cell transplant. For solid tumors, if appropriate, disease specific radiation therapy at day +60. For CNS tumors, the conditioning regimen and autologous peripheral blood stem cell transplant will be given for 3 cycles.

Conditions

Ewing's Family Tumors; Renal Tumors; Hepatoblastoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Primary Malignant Brain Neoplasms; Retinoblastoma; Medulloblastoma; Atypical Teratoid/Rhabdoid Tumor (AT/RT); CNS Tumors; Germ Cell Tumors; Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET)

Keywords

autologous transplantation; high risk solid tumor; relapsed solid tumor

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Number of patients who have received autologous transplant for high risk or relapsed solid tumor and certain CNS tumors and are alive at 1 year.

  1 Year

Secondary Outcomes (4)

• Number of Patients Who Achieved Transplant Engraftment

  Day 42

• Disease Free Survival

  1 Year

• Treatment-Related Mortality

  Day 100

• Disease Free Survival

  3 Years

Study Arms (5)

Arm A: Patients with High Risk or Relapsed Solid Tumor

OTHER

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; Drug: Etoposide; Drug: Mesna; Biological: G-CSF; Drug: Busulfan; Drug: Melphalan; Drug: Thiotepa; Biological: Autologous stem cell infusion; Radiation: Radiation

Arm B: Certain CNS Tumors

OTHER

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, carboplatin (dose based on GFR and age 17 mg/kg/day IV or 510 mg/m\^2/day IV) , thiotepa conditioning (10 mg/kg/day or 300 mg/m\^2 IV on days -3 and -2) followed by an autologous peripheral blood stem cell transplant (infusion on Day 0). This will be repeated up to 2 additional 30 day cycles.

Drug: Ifosfamide; Drug: Etoposide; Drug: Mesna; Biological: G-CSF; Drug: Thiotepa; Biological: Autologous stem cell infusion; Drug: Carboplatin

Arm C: Germ Cell Tumors

OTHER

1. High-Dose Chemotherapy (3 cycles) * Carboplatin AUC=8 \& Etoposide 400 mg/m\^2 daily, days -4, -3, and -2 every 21 days 2. Autologous Stem Cell Infusion ≥ 3 x 106 CD34+ cells/kg Day 0 Cycles 1, 2 and 3 3. TI Chemotherapy \& PBSC Collection. * Paclitaxel 200mg/m\^2 IV over 3 hours on Day 1 every 14 days for 2 cycles * Ifosfamide 2000 mg/m\^2 IV daily on Days 1-3 every 14 days for 2 cycles * Mesna 2000 mg/m\^2 on Days 1-3 every 14 days for 2 cycles * G-CSF 10 μg/kg sub q daily on day 3 until adequate CD34+ cell collection or day 15, whichever occurs first * Leukapheresis starting on approx. day 11 and continued daily until reaching the collection goal of ≥ 8 x 106 CD34+ cells/kg) or day 15, whichever occurs first

Drug: Ifosfamide; Drug: Etoposide; Drug: Mesna; Biological: G-CSF; Biological: Autologous stem cell infusion; Drug: Carboplatin; Drug: Paclitaxel; Procedure: Leukapheresis

Arm D: Certain CNS Tumors

OTHER

1. Mobilization Chemotherapy and PBSC Collection (day -100 to day -30) 2. Pre-Transplant Conditioning Chemotherapy (3 cycles) * Day -8, -7, -6: Carboplatin as calculated from AUC of 7 approx. * Day -5, -4, -3: Thiotepa 10 mg/kg, Etoposide 8.3 mg/kg * Day 0: Autologous Hematopoietic Cell Reinfusion * Day +1: Begin G-CSF(filgrastim) 5 mcg/kg

Drug: Etoposide; Biological: G-CSF; Drug: Thiotepa; Biological: Autologous stem cell infusion; Drug: Carboplatin

Arm E: Neuroblastoma

OTHER

1. Mobilization Chemotherapy and PBSC Collection (day -100 to day -30) 2. Pre-Transplant Conditioning Chemotherapy (day -7 to day -0) * Day -7: anti-seizure prophylaxis with lorazepam or levetiracetam * Day -6 - -3: Busulfan IV q24 hours x 4 doses * Day -1: Melphalan 140 mg/m2 IV * Day 0: Autologous Hematopoietic Cell Reinfusion

Biological: G-CSF; Drug: Busulfan; Drug: Melphalan; Biological: Autologous stem cell infusion; Drug: Anti-seizure prophylaxis; Drug: Ursodiol

Interventions

Ifosfamide DRUG

* Arms A\&B: 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 * Arm C: 2000 mg/m\^2 IV daily on Days 1-3 every 14 days for 2 cycles

Also known as: Mitoxana, Ifex

Arm A: Patients with High Risk or Relapsed Solid Tumor; Arm B: Certain CNS Tumors; Arm C: Germ Cell Tumors

Etoposide DRUG

* Arms A\&B: 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. * Arm C: 400 mg/m\^2 daily on days -4, -3, and -2 every 21 days * Arm D: Etoposide 8.3 mg/kg (or 250mg/m² if age \>36 mos.) approx. hour 75 on days -5, -4, and -3

Also known as: Eposin, Etopophos, Vepesid, VP-16

Arm A: Patients with High Risk or Relapsed Solid Tumor; Arm B: Certain CNS Tumors; Arm C: Germ Cell Tumors; Arm D: Certain CNS Tumors

Mesna DRUG

* Arms A\&B: 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. * Arm C: 2000 mg/m\^2 IV daily on Days 1-3 every 14 days for 2 cycles

Also known as: Uromitexan, Mesnex

Arm A: Patients with High Risk or Relapsed Solid Tumor; Arm B: Certain CNS Tumors; Arm C: Germ Cell Tumors

G-CSF BIOLOGICAL

* Arms A\&B: 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. 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 * Arm C: 10 μg/kg SQ daily beginning 6 hours after ifosfamide on day 3 until adequate CD34+ cell collection or day 15, whichever occurs first. * Arm D: Beginning day +1 following hematopoietic cell reinfusion, patients receive filgrastim at a dose of 5mcg/kg SQ once daily (or 5mcg/Kg IV either daily or twice daily, per institutional preference) * Arm E: 5 micrograms/kg/dose beginning on Day 0 and continue per institutional preference

Also known as: Granulocyte colony-stimulating factor

Arm A: Patients with High Risk or Relapsed Solid Tumor; Arm B: Certain CNS Tumors; Arm C: Germ Cell Tumors; Arm D: Certain CNS Tumors; Arm E: Neuroblastoma

Busulfan DRUG

Arm A: 1.1 mg/kg IV every 6 hours on days -8 through -6 Arm E: first dose of busulfan is dosed by mg/kg as appropriate for age and weight. Once the results of pharmacokinetic (PK) studies are known, subsequent daily doses are based upon those results,

Also known as: Busulfex

Arm A: Patients with High Risk or Relapsed Solid Tumor; Arm E: Neuroblastoma

Melphalan DRUG

Arm A: 50 mg/m\^2 intravenously (IV) over 30 min on Days -4 and -5 Arm E:140 mg/m2 AT LEAST 24 hrs after last busulfan dose. Day: -1

Also known as: 50 mg/m2 IV over 30 min

Arm A: Patients with High Risk or Relapsed Solid Tumor; Arm E: Neuroblastoma

Thiotepa DRUG

Arm A: 250 mg/m\^2 intravenously (IV) over 2 hrs on days -2 and -3 Arm B: 10 mg/kg/day or 300 mg/m\^2 IV on days -3 and -2 Arm D: Thiotepa 10 mg/kg (or 300mg/m² if age \>36 mos.) approx. hour 72 on days -5, -4, and -3

Also known as: Thioplex

Arm A: Patients with High Risk or Relapsed Solid Tumor; Arm B: Certain CNS Tumors; Arm D: Certain CNS Tumors

Autologous stem cell infusion BIOLOGICAL

Arms A, B \& C: On Day 0, stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines. Arm D: On day 0, peripheral blood hematopoietic progenitor cells (PHPCs) or bone marrow cells will be thawed and re-infused about 72 hours following completion of the last dose of chemotherapy. Arm E: stem cells will be infused on Day 0 of Consolidation. Where the DMSO volume in the stem cell product would exceed accepted level for infusion within a 24 hour period, stem cell products may be infused over 2 days to meet this standard.

Arm A: Patients with High Risk or Relapsed Solid Tumor; Arm B: Certain CNS Tumors; Arm C: Germ Cell Tumors; Arm D: Certain CNS Tumors; Arm E: Neuroblastoma

Radiation RADIATION

Arm A: 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.

Arm A: Patients with High Risk or Relapsed Solid Tumor

Carboplatin DRUG

Arm B: depending on age and GFR 17mg/kg/day IV over 4 hours or 510 mg/m\^2/day IV over 4 hours Arm C: AUC=8 daily on days -4, -3, and -2 every 21 days Arm D: as calculated from AUC of 7 approx. hour 0 on days -8, -7, and -6

Also known as: Paraplatin

Arm B: Certain CNS Tumors; Arm C: Germ Cell Tumors; Arm D: Certain CNS Tumors

Paclitaxel DRUG

Arm C: 200 mg/m2 IV over 3 hours on Day 1 every 14 days for 2 cycles

Also known as: Taxol, Onxal

Arm C: Germ Cell Tumors

Leukapheresis PROCEDURE

Arm C: Blood will be taken by a needle placed in one arm and processed through a machine, which spins the blood so that the white blood cells will be separated out in the machine for purposes of this research and the rest of the blood will be returned through a needle in the other arm.

Arm C: Germ Cell Tumors

Anti-seizure prophylaxis DRUG

Arm E: Lorazepam OR Levetaracetam * Lorazepam should be given 0.02-0.05 mg/kg/dose, given 30 minutes prior to each busulfan dose and then continuing every 6 hours, maximum dose: 2 mg. * Levetiracetam should be given 10 mg/kg/dose PO, administered BID, staring 12 hours prior to busulfan, maximum single dose: 1000mg.

Arm E: Neuroblastoma

Ursodiol DRUG

Arm E: 150 mg/m2/dose PO, administered BID, beginning on Day -7 and continuing a minimum of 28 days post-transplant, or until the end of Consolidation.

Arm E: Neuroblastoma

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have histological verification of malignancy at original diagnosis.
• Eligible Diseases
• Arm A: Solid Tumor
• 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
• CNS Lymphoma - primary or secondary CNS lymphoma.
• Other High Risk Metastatic or Relapsed Solid Tumors - to be approved by 2 or more pediatric hematology/oncology and bone marrow transplant (BMT) physicians
• Arm B: Certain CNS tumors
• Medulloblastoma: Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) who have high risk Medulloblastoma, defined as any one of the following:
• \> 1.5 cm2 residual disease following resection for any Medulloblastoma histology

You may not qualify if:

• Arm A, B, C, and D:
• Pregnant or breastfeeding
• Active, uncontrolled infection and/or human immunodeficiency virus (HIV) positive constitute progressive disease.
• Concomitant enrollment on clinical study (such as COG study) that does not allow co-enrollment on this standard of care protocol (Arm B only)
• Arm E: Pregnant or breastfeeding
• Active, uncontrolled infection and/or HIV positive
• Known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.
• Patients that are 12-18 months of age with INSS Stage 4 and all 3 favorable biologic features (ie, non- amplified MYCN, favorable pathology, and DNA index \> 1).

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Hepatoblastoma; Rhabdomyosarcoma; Sarcoma; Brain Neoplasms; Retinoblastoma; Medulloblastoma; Rhabdoid Tumor; Central Nervous System Neoplasms; Neoplasms, Germ Cell and Embryonal

Interventions

Ifosfamide; Etoposide; etoposide phosphate; Mesna; Granulocyte Colony-Stimulating Factor; Busulfan; Melphalan; Thiotepa; Radiation; Carboplatin; Paclitaxel; Leukapheresis; Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Complex and Mixed; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Nerve Tissue; Retinal Neoplasms; Eye Neoplasms; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases; Glioma; Neuroectodermal Tumors, Primitive

Intervention Hierarchy (Ancestors)

Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Butylene Glycols; Glycols; Alcohols; Mesylates; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Triethylenephosphoramide; Aziridines; Azirines; Physical Phenomena; Coordination Complexes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Cholanes

Study Officials

• Ashish Gupta, MBBS, MPH

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2012
• First Posted: January 6, 2012
• Study Start: October 20, 2011
• Primary Completion: February 1, 2024
• Study Completion: February 1, 2024
• Last Updated: February 26, 2024

Record last verified: 2024-02

Locations

US (1)