Anti-Angiogenic Therapy Post Transplant (ASCR) for Pediatric Solid Tumors

NCT01661400 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201209088
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine whether taking either of two low dose drugs that would prevent new blood vessels from growing after stem cell transplant is feasible, and what the side effects of taking each of these drugs after autologous transplant might be. The reason the investigators are looking at these drugs is because one of the things that allows tumors to grow quickly is their ability to stimulate the growth of new blood vessels. By suppressing the growth of new blood vessels after stem cell transplant, the investigators hope to prevent the tumors from coming back or continuing to grow.

Conditions

Glioma; Neuroectodermal Tumors, Primitive; Wilms Tumor; Rhabdomyosarcoma; Sarcoma, Ewing; Osteosarcoma; Retinoblastoma

Keywords

Glioma includes ependymoma and medulloblastoma

Outcome Measures

Primary Outcomes (2)

• Safety as measured by absence of grade 4 or 5 non-hematological or grade 5 hematological toxicity

  Through 1 year post-transplant

• Incidence of major transplant related toxicities (Grades IV and IV)

  Within the first year of transplant

Secondary Outcomes (1)

• Best overall response

  86 days

Study Arms (3)

Control

NO INTERVENTION

No intervention

Metronomic Cyclophosphamide

EXPERIMENTAL

Cyclophosphamide will be given PO once daily at 2.5 mg/kg/day for children \< 40kg or 100 mg daily for children \> 40kg beginning Day + 30 (30 days post transplant) and continue until at least Day +86

Drug: Metronomic Cyclophosphamide

Thalidomide

EXPERIMENTAL

Thalidomide will be initiated at 3mg/kg PO daily beginning Day + 30 (30 days post transplant) and continue until Day +86

Drug: Thalidomide

Interventions

Metronomic Cyclophosphamide DRUG

Also known as: Cytoxan®, CPM

Metronomic Cyclophosphamide

Thalidomide DRUG

Also known as: Thalomid®

Thalidomide

Eligibility Criteria

• Age: 6 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient must have an original diagnosis, benefited by autologous transplantation, confirmed by biopsy\* of high-grade glial tumor, low-grade glial tumor, ependymoma, medulloblastoma, primitive neuro-ectodermal tumor (PNET), Wilms' tumor, rhabdomyosarcoma, Ewing's sarcoma, retinoblastoma, or miscellaneous poor-prognosis solid tumors. Lymphomas and other lymphoid malignancies will not be studied in this protocol.
• \* Brain stem glioma patients who have progressed after radiation therapy do not require histologic confirmation. Brain stem gliomas are defined as intrinsic tumors of the pons causing diffuse enlargement. These patients are diagnosed on clinical and radiographic appearance of the lesion and the biopsy requirement will be waived for this group.
• Patient must be ≥ 6 months of age and ≤ 21 years of age at the time of study entry.
• Patient must have a Karnofsky performance status or Lansky\* play status ≥ 50
• \* For purpose of determining performance scores, wheelchair-bound patients will be considered ambulatory.
• Patient must have an adequate supply of stem cells for transplant harvested prior to study enrollment, with adequate supply defined as 3 x 10\^6 CD34+ cells/kg for peripheral blood stem cells (PBSC). Cell mobilization method will be left up to the treating physician's discretion and may include mobilization growth factor alone or mobilization after chemotherapy. If patient is unable to mobilize the proper amount of peripheral stem cells, bone marrow may be harvested as the source of hematopoietic stem cells. In this instance, 3 x 10\^8 mononuclear cells/kg will be considered adequate. If necessary, a combination of peripheral stem cells and bone marrow can be used.
• Prior radiation therapy and/or chemotherapy, including cyclophosphamide, are permitted.
• Prior anti-angiogenic therapy, including thalidomide and oral cyclophosphamide, is permitted.
• If on corticosteroids for mass effect and/or edema related to the tumor, patient must be on a stable or decreasing dose for at least 2 weeks prior to study entry.
• Patient must have a life expectancy \> 3 months.
• Patient must have an adequate bone marrow reserve as defined by:
• Hemoglobin ≥ 8.0 g/dl and
• Peripheral absolute neutrophil count (ANC) ≥ 750/mm3
• Patient must have adequate cardiac function tested within 4 weeks of study enrollment as defined by:
• Shortening fraction of ≥ 27% by echocardiogram or

You may not qualify if:

• Patient must not have any active, uncontrolled cardiac, hepatic, renal, or psychiatric disease defined as ≥ grade 3 based on NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
• Patient must not be receiving any other investigational agents.
• Patient must not have any active infection or concurrent illness obscuring toxicity or dangerously altering drug metabolism.
• Patient must not have any thromboembolic event (deep vein thrombosis or pulmonary embolism) less than 3 weeks prior to enrollment.
• Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents used in the study.
• Patient must not be pregnant or breastfeeding.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Glioma; Neuroectodermal Tumors, Primitive; Wilms Tumor; Rhabdomyosarcoma; Sarcoma, Ewing; Osteosarcoma; Retinoblastoma; Medulloblastoma

Interventions

Cyclophosphamide; Thalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Retinal Neoplasms; Eye Neoplasms; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Andrew Cluster, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2012
• First Posted: August 9, 2012
• Study Start: October 26, 2012
• Primary Completion: December 27, 2023
• Study Completion: December 27, 2023
• Last Updated: January 31, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)