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NeuroblastomaPhase 2NCT00017368

Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Neuroblastoma

A Phase 2 study testing filgrastim, sargramostim and carboplatin in people with Neuroblastoma, run by Children's Oncology Group at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Read more about this study

Who is it for?
Ages Up to 30 years
Conditions the study is for
Neuroblastoma
What is being tested?
filgrastim, sargramostim and carboplatin
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
9 sitesin 2 countries
Study dates
Apr 2001to Jan 2012
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Newly diagnosed high-risk neuroblastoma
  • Histologically proven AND/OR
  • Bone marrow specimen showing clumps of tumor cells accompanied by elevated urinary catecholamines
  • Age 1-30:
  • Must meet one of the following INSS staging criteria:
  • Stage IV regardless of biologic factors
  • Stage IIa/IIb with MYCN oncogene amplification (greater than 10) and unfavorable pathology
  • Stage III with MYCN oncogene amplification (greater than 10) or unfavorable pathology
  • Initially stage I, II, or IVS, that has progressed without interval chemotherapy
  • Under age 1:
  • INSS stage III, IV, or IVS with MYCN amplification (greater than 10)
  • Must enter neuroblastoma biology study COG-ANBL00B1 within 2 weeks of diagnosis and before entry on this study

PATIENT CHARACTERISTICS:

Age:

  • 30 and under at original diagnosis

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Not specified

Renal:

  • Not specified

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics
  • No more than 1 prior course of chemotherapy on the intergroup low- or intermediate-risk neuroblastoma studies prior to determination of MYCN status and Shimada histology

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Prior emergent radiotherapy to sites of function- or life-threatening neuroblastoma allowed

Surgery:

  • Not specified

Other:

  • No other prior systemic therapy for neuroblastoma

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States8 sites

  • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish RiteCampus

    Atlanta, Georgia, 30342

  • Floating Hospital for Children

    Boston, Massachusetts, 02111

  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Baylor College of Medicine

    Houston, Texas, 77030

  • CCOP - Marshfield Clinic Research Foundation

    Marshfield, Wisconsin, 54449

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • CCOP - Columbia River Oncology Program

    Portland, Oregon, 97225

  • CCOP - Scott and White Hospital

    Temple, Texas, 76508

Other trials in United States

Australia1 site

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6001

Other trials in Australia

About this study

Official title: A Pilot Study Of Tandem High Dose Chemotherapy With Stem Cell Rescue Following Induction Therapy In Children With High Risk Neuroblastoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating children who have newly diagnosed neuroblastoma.

Read the detailed description

OBJECTIVES:

  • Determine the toxicity and feasibility of high-dose thiotepa and cyclophosphamide with autologous peripheral blood stem cell (PBSC) transplantation and sargramostim (GM-CSF) followed by high-dose carboplatin, etoposide, and melphalan with second PBSC transplantation, GM-CSF, and isotretinoin after induction in children with newly diagnosed high-risk neuroblastoma.
  • Determine the role of the meta-iodobenzylguanidine (MIBG) scan in assessing response to tandem transplantation and minimal residual disease therapy in these patients.
  • Determine the feasibility of quantitative polymerase chain reaction for neuroblastoma-specific ribonucleic acids at specific stages of treatment as a prognostic indicator of outcome in these patients.
  • Determine the immune recovery by quantitation of lymphocyte subsets in these patients and limited functional analysis after completion of this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to peripheral blood stem cell (PBSC) selection (selected PBSCs vs unselected PBSCs). (Selected PBSC stratum closed to accrual as of 7/17/02.)

  • Induction/harvest:
  • Course 1: Patients receive etoposide (VP-16) IV over 1 hour on days 2-4, cisplatin IV over 6 hours (beginning after VP-16 infusion) on days 1-5, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 6 and continuing until blood counts recover.
  • Course 2: Patients receive vincristine IV and doxorubicin IV over 15 minutes on day 1, cyclophosphamide IV over 6 hours on days 1 and 2, and sargramostim (GM-CSF) SC beginning on day 3 and continuing until PBSC are harvested. Beginning after completion of course 2 and when blood counts recover, autologous PBSC are harvested.
  • Course 3: Patients receive VP-16 IV over 1 hour and ifosfamide IV over 1 hour on days 1-5 and G-CSF SC beginning on day 6 and continuing until blood counts recover.
  • Course 4: Patients receive VP-16 IV over 1 hour on days 1-3, carboplatin IV over 2 hours (beginning after VP-16 infusion) on days 1 and 2, and G-CSF SC beginning on day 4 and continuing until blood counts recover.
  • Course 5: Patients receive treatment as in course 2 but supported by G-CSF. Courses 1-5 each last 3-4 weeks. Patients undergo resection of the primary tumor after course 4 or 5 unless primary resection was completed at diagnosis (which is not recommended), no primary site is found, or the primary site is unresectable. Patients complete courses 1-5 and then proceed to the first conditioning/PBSC transplantation (PBSCT) in the absence of disease progression or unacceptable toxicity.
  • First conditioning/PBSCT: Patients receive high-dose thiotepa IV on days -7 to -5 and cyclophosphamide IV over 1 hour on days -5 to -2. CD34+ PBSC are reinfused on day 0. GM-CSF is administered SC beginning on day 5 and continuing until blood counts recover. If blood counts have not recovered by day 28, unselected PBSC are reinfused. In the absence of disease progression or unacceptable toxicity, patients proceed to the second conditioning/PBSCT.
  • Second conditioning/PBSCT: Beginning within 6-8 weeks after initiating the first conditioning, patients receive high-dose carboplatin IV continuously and etoposide phosphate IV continuously on days -7 to -4 and melphalan IV on days -7 to -5. PBSC and GM-CSF are administered as in the first PBSCT.

Beginning no earlier than day 28 after the second PBSCT, patients undergo local radiotherapy to the primary site and sites that are positive by meta-iodobenzylguanidine scan after induction twice a day for 7 days (or once a day for 12 days if twice daily dosing is not possible). Beginning on day 90 after the second PBSCT, patients receive oral isotretinoin twice a day for 2 weeks. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 31-39 patients will be accrued for this study within 22 months.

Conditions
Neuroblastoma
Keywords
regional neuroblastoma, disseminated neuroblastoma, localized unresectable neuroblastoma, stage 4S neuroblastoma
Medical subject headings
Neuroblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00017368
Study groupRoleWhat they receive
All PatientsExperimentalNot described
Receives: Biological: filgrastim; Biological: sargramostim; Drug: carboplatin; Drug: cisplatin; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: etoposide phosphate; Drug: ifosfamide; Drug: isotretinoin; Drug: melphalan; Drug: thiotepa; Drug: vincristine sulfate; Procedure: conventional surgery; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Transplant-related mortality

    The endpoint used for early stopping rule 9.51 will be transplant-related mortality (TRM). A TRM is defined as any death occurring within 30 days after either the first or second HDC/SCR. The acceptable TRM rate is 7.5%. This rate is based on TRM rates previously observed in the prior CCG study 594, CCG study 3891, and POG study 9640 of 7%, 6%, and 0%, respectively.

Secondary outcomes (2)

  1. Incidence of symptomatic CMV, disseminated adenovirus infection, or EBV-LPD

    The endpoint to be used in assessing early stopping rule 9.52 will be the incidence of symptomatic CMV, disseminated adenovirus infection, or EBV-LPD. Patients with positive CMV antigenemia or CMV urine culture only (without symptoms of CMV infection), or patients who have a positive culture for adenovirus without evidence of dissemination, or patients with a positive EBV PCR who do not exhibit significant clinical signs (such as adenopathy) or symptoms will not trigger the stopping rule.

  2. Event-free Survival

    Assessment of feasibility and toxicity at the end of the study is time to event. Time to event is defined as the time from registration on the study until the first of the following events occurs: relapse, progression, secondary malignancy, or death, including toxic death. If none of those events occurs, then the time of last contact with the patient is used. Time to event will be used to calculate the one-year Event-free Survival (EFS) rate.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2003 (estimated)
  2. Study startApr 2001
  3. Primary completionSep 2005
  4. Study completionJan 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00017368
Sponsor's protocol ID
ANBL00P1
Other IDs
COG-ANBL00P1, CDR0000068681
Status last verified
Feb 2014
First submitted
6 Jun 2001
Last updated
13 Feb 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Marcus KJ, Shamberger R, Litman H, von Allmen D, Grupp SA, Nancarrow CM, Goldwein J, Grier HE, Diller L. Primary tumor control in patients with stage 3/4 unfavorable neuroblastoma treated with tandem double autologous stem cell transplants. J Pediatr Hematol Oncol. 2003 Dec;25(12):934-40. doi: 10.1097/00043426-200312000-00005.

    PubMed 14663275

  • Kletzel M, Katzenstein HM, Haut PR, Yu AL, Morgan E, Reynolds M, Geissler G, Marymount MH, Liu D, Kalapurakal JA, Shore RM, Bardo DM, Schmoldt J, Rademaker AW, Cohn SL. Treatment of high-risk neuroblastoma with triple-tandem high-dose therapy and stem-cell rescue: results of the Chicago Pilot II Study. J Clin Oncol. 2002 May 1;20(9):2284-92. doi: 10.1200/JCO.2002.06.060.

    PubMed 11980999

  • Donovan J, Temel J, Zuckerman A, Gribben J, Fang J, Pierson G, Ross A, Diller L, Grupp SA. CD34 selection as a stem cell purging strategy for neuroblastoma: preclinical and clinical studies. Med Pediatr Oncol. 2000 Dec;35(6):677-82. doi: 10.1002/1096-911x(20001201)35:63.0.co;2-h.

    PubMed 11107145

  • Grupp SA, Stern JW, Bunin N, Nancarrow C, Adams R, Gorlin JB, Griffin G, Diller L. Rapid-sequence tandem transplant for children with high-risk neuroblastoma. Med Pediatr Oncol. 2000 Dec;35(6):696-700. doi: 10.1002/1096-911x(20001201)35:63.0.co;2-0.

    PubMed 11107149

  • Grupp SA, Stern JW, Bunin N, Nancarrow C, Ross AA, Mogul M, Adams R, Grier HE, Gorlin JB, Shamberger R, Marcus K, Neuberg D, Weinstein HJ, Diller L. Tandem high-dose therapy in rapid sequence for children with high-risk neuroblastoma. J Clin Oncol. 2000 Jul;18(13):2567-75. doi: 10.1200/JCO.2000.18.13.2567.

    PubMed 10893288

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing filgrastim, sargramostim and carboplatin in people with Neuroblastoma, run by Children's Oncology Group at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Transplant-related mortality. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00017368, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2014.

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