Monoclonal Antibody Ch14.18, Sargramostim, Aldesleukin, and Isotretinoin After Autologous Stem Cell Transplant in Treating Patients With Neuroblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01041638
First received: December 31, 2009
Last updated: February 25, 2015
Last verified: November 2014
  Purpose

This phase III trial is studying the side effects of giving monoclonal antibody Ch14.18 together with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplant in treating patients with neuroblastoma. Monoclonal antibodies, such as Ch14.18, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood. Aldesleukin may stimulate the white blood cells to kill tumor cells. Isotretinoin may help neuroblastoma cells become more like normal cells, and to grow and spread more slowly. Giving monoclonal antibody Ch14.18 together with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplant may be an effective treatment for neuroblastoma.


Condition Intervention Phase
Disseminated Neuroblastoma
Localized Resectable Neuroblastoma
Localized Unresectable Neuroblastoma
Regional Neuroblastoma
Stage 4S Neuroblastoma
Biological: aldesleukin
Biological: sargramostim
Biological: monoclonal antibody Ch14.18
Drug: isotretinoin
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Comprehensive Safety Trial of Chimeric Antibody 14.18 (Ch14.18) With GM-CSF, IL-2 and Isotretinoin in High-Risk Neuroblastoma Patients Following Myeloablative Therapy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Percentage of Patients Who Experienced a Significant (CTC Grade 3-5) Nonhematologic Toxicity of Interest (Pain, Hypotension, Allergic Reactions, Capillary Leak Syndrome, or Fever). [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Designed to collect comprehensive safety/toxicity data, as well as additional efficacy data for the immunotherapy. To address the primary objective, descriptive analyses summarizing the number and type of AEs will be performed. The percentage of patients reporting each unacceptable (Grade 3 or higher) CTC toxicity code, tabulated by course, are reported.


Secondary Outcome Measures:
  • Event-free Survival [ Time Frame: From enrollment until the first occurrence of relapse, progressive disease, secondary malignancy, or death, or until last contact if no event occurred, up to 5 years ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier curves.

  • Overall Survival [ Time Frame: From enrollment until death, or until last contact with the patient, up to 5 years ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier curves.


Enrollment: 105
Study Start Date: December 2009
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chimeric Antibody 14.18 with GM-CSF, IL-2 and Isotretinoin
Patients receive sargramostim subcutaneously or IV over 2 hours on days 0-13 of courses 1, 3, and 5 (dose: 250 micrograms/m²/dose); monoclonal antibody Ch14.18 IV over 10 hours on days 3-6 of courses 1, 3, and 5 and on days 7-10 of courses 2 and 4 (dose: 25 mg/m2/dose); and oral isotretinoin twice daily on days 11-24 of course 1, on days 14-27 of courses 2, 4, and 6, and on days 10-23 of courses 3 and 5 (Weight based dosage: > 12 kg: 80 mg/m2/dose BID; total daily dose 160 mg/m2/day, divided BID. ≤ 12 kg: 2.67 mg/kg/dose BID; total daily dose is 5.33 mg/kg/day, divided BID. Round dose up to the nearest 10 mg). Patients also receive aldesleukin IV continuously on days 0-3 and on days 7-10 of courses 2 and 4 (actual dosage is body surface area based and varies by course). Treatment repeats every 24-32 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Biological: aldesleukin

Given IV - Doses and days vary by week of course:

Week 1 of Each Course: Dose: 3 Million International Units/m2/dose. Days: 0-3. Week 2 of Each Course: Dose: 4.5 Million International Units/m2/dose. Days: 7-10. Actual dosage is Body Surface Area calculated.

Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Biological: sargramostim
Given IV or SC
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Biological: monoclonal antibody Ch14.18
Given IV
Other Names:
  • Ch14.18
  • MOAB Ch14.18
Drug: isotretinoin
Given orally
Other Names:
  • 13-CRA
  • Amnesteem
  • Cistane
  • Claravis
  • Sotret

Detailed Description:

PRIMARY OBJECTIVES:

I. To comprehensively define the safety profile of monoclonal antibody Ch14.18 when administered with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplantation (ASCT) in patients with high-risk neuroblastoma.

SECONDARY OBJECTIVES:

I. To further describe and refine the event-free survival and overall survival estimates in patients treated with this regimen.

II. To further describe the baseline characteristics of patients treated with these regimen.

III. To further describe the safety and toxicity of this regimen, in terms of number of courses delivered per patient, number of dose reductions or stoppage, and number of toxic deaths, in these patients.

IV. To further describe the immune reconstitution following ASCT based on laboratory data obtained just before, during, and after treatment with this regimen.

V. To obtain correlative laboratory data to evaluate and describe mechanisms related to response, toxicity of immune activation, and allergic phenomena.

OUTLINE: This is a multicenter study.

Patients receive sargramostim subcutaneously or IV over 2 hours on days 0-13 of courses 1, 3, and 5; monoclonal antibody Ch14.18 IV over 10 hours on days 3-6 of courses 1, 3, and 5 and on days 7-10 of courses 2 and 4; and oral isotretinoin twice daily on days 11-24 of course 1, on days 14-27 of courses 2, 4, and 6, and on days 10-23 of courses 3 and 5. Patients also receive aldesleukin IV continuously on days 0-3 and on days 7-10 of courses 2 and 4. Treatment repeats every 24-32 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients may undergo blood and bone marrow sample collection periodically for correlative laboratory studies.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of neuroblastoma

    • High risk at diagnosis
  • Meets the International Neuroblastoma Response Criteria (INRC) for complete response, very good partial response, or partial response for primary site, soft tissue metastasis, and bone metastasis AND meets the protocol-specified criteria for bone marrow response

    • No more than 10% tumor (of total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy

      • Patients who have no tumor seen on a prior bone marrow aspirate/biopsy specimen and then have ≤ 10% tumor seen on any of the bilateral marrow aspirate/biopsy specimens done at pre-autologous stem cell transplantation (ASCT) and/or pre-study enrollment evaluation are eligible
  • Residual disease by MIBG scan, CT scan, MRI, bone marrow aspiration, or biopsy allowed
  • No progressive disease other than protocol-specified bone marrow response as described above
  • Must have completed therapy that included intensive induction chemotherapy followed by ASCT and radiotherapy within the past 100 days

    • Radiotherapy may be waived for patients who either had a small adrenal mass that was completely resected up-front or who never had an identifiable primary tumor
    • No more than 9 months between the date of starting the first induction chemotherapy after diagnosis to the date of ASCT (for patients who have undergone tandem ASCT, this is the date of the first stem cell infusion)

      • For patients who were initially diagnosed as non-high risk neuroblastoma, but later converted (and/or relapsed) to high-risk neuroblastoma, the 9 months restriction should start from the date of induction therapy for high-risk neuroblastoma (not from the initial induction therapy for non-high-risk disease) to the date of ASCT
  • Lansky performance status (PS) 50-100% (for patients ≤ 16 years of age) OR Karnofsky PS 50-100% (for patients > 16 years of age)
  • Life expectancy ≥ 2 months
  • Absolute phagocyte count ≥ 1,000/μL
  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:

    • 0.4 mg/dL (1 to 5 months of age)
    • 0.5 mg/dL (6 to 11 months of age)
    • 0.6 mg/dL (1 year of age)
    • 0.8 mg/dL (2 to 5 years of age)
    • 1.0 mg/dL (6 to 9 years of age)
    • 1.2 mg/dL (10 to 12 years of age)
    • 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years of age)
    • 1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years of age)
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT < 5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 55% by radionuclide angiography
  • FEV_1/FVC > 60% by pulmonary function test (if performed)
  • No evidence of dyspnea at rest
  • No CNS toxicity ≥ grade 2
  • Seizure disorder allowed provided patient is on anticonvulsants and it is well controlled
  • Sinusoidal obstruction syndrome allowed provided it is stable or improving
  • No other concurrent anticancer therapy
  • No prior anti-GD2 antibody therapy
  • No prior vaccine therapy for neuroblastoma
  • No concurrent pentoxifylline or immunosuppressive drugs (e.g., cyclosporine or corticosteroids [other than for the treatment of acute allergic reactions to immunotherapy or treatment of increased intracranial pressure in patients with CNS tumors])
  • No other concurrent cytokines or growth factors
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01041638

  Show 28 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Mehmet Ozkaynak, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01041638     History of Changes
Other Study ID Numbers: NCI-2011-01997, NCI-2011-01997, COG-ANBL0931, CDR0000662673, ANBL0931, ANBL0931, U10CA098543
Study First Received: December 31, 2009
Results First Received: February 3, 2015
Last Updated: February 25, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neuroblastoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Aldesleukin
Antibodies
Antibodies, Monoclonal
Immunoglobulins
Interleukin-2
Isotretinoin
Analgesics
Analgesics, Non-Narcotic
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antineoplastic Agents
Antiviral Agents
Central Nervous System Agents
Dermatologic Agents
Immunologic Factors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents

ClinicalTrials.gov processed this record on August 31, 2015