search
Back to results

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

Primary Purpose

Glioma, Neuroectodermal Tumors, Primitive, Wilms Tumor

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Metronomic Cyclophosphamide
Thalidomide
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioma focused on measuring Glioma includes ependymoma and medulloblastoma

Eligibility Criteria

6 Months - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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
    • Ejection fraction of ≥ 50% by radionuclide angiogram
  • Patient must have adequate pulmonary function tested within 4 weeks of study enrollment as defined by:

    • Pulse oximetry > 94% on room air or O2 by nasal cannula and
    • No evidence of dyspnea at rest.
  • Patient must have adequate hepatic function as defined by:

    • Total bilirubin ≤ 1.5x upper limit of normal (ULN) for age and
    • SGOT (AST) or SGPT (ALT) ≤ 2.5 x ULN (SGOT ≤ 4x ULN if on Zantac)
  • Patient must have adequate renal function as defined by:

    • Serum creatinine < 1.5 mg/dl
    • Glomerular filtration rate (GFR), calculated via I-125 iothalamate clearance, 24-hour creatinine clearance, or Schwartz formula*, ≥ 70 mL/min and ≥ 50 mL/min/1.73 m2 done within 4 weeks of study entry
    • The Schwartz formula is an estimated glomerular filtration rate in children based upon serum creatinine and height. Height (Ht) should be measured in cm and serum creatinine (Cr) in mg/dL. Proportionality constant (k) is 0.55 for children and adolescent girls and 0.7 for adolescent boys aged 13-21. This constant is based upon a series of evaluations performed by Schwartz. Formula: GFR= (k x Ht)/Cr
  • Enrollment in the Celgene THALOMID REMSTM Program:

    1. If enrolled in Arm III of this study, patient must be registered at the Celgene THALOMID REMSTM Program prior to day +30 post-ASCR.
    2. If enrolled in Arm III of this study, patient must be willing to practice birth control as outlined in the THALOMID REMSTM Program from the beginning of the thalidomide treatment until at least 4 weeks following discontinuation of thalidomide therapy. Two reliable forms of contraception must be used simultaneously unless continuous abstinence from heterosexual sexual contact is chosen. Contraceptive methods must include at least one highly effective method (e.g. oral contraceptive pills, injections, hormonal patches, IUD, or implants), AND one additional effective barrier method (e.g. latex condom, diaphragm, cervical cap).

      If hormonal or IUD contraception is medically contraindicated, another highly effective method or two barrier methods must be used at the same time.

    3. Pregnancy surveillance:

    i. Patient must have a negative in office pregnancy test sensitive to within 50 mIU/mL (serum or urine) within 24 hours prior to beginning thalidomide even if continuous abstinence is the preferred method of birth control. ii. A pregnancy test must be performed weekly during the first 4 weeks of therapy and repeated monthly for patients with regular menses or every 2 weeks for patients with irregular menses iii. Negative pregnancy tests are valid for only 7 days. iv. If irregular bleeding or skipped menses, pregnancy test should be performed and pregnancy counseling given. v. If pregnancy occurs during treatment, thalidomide must be immediately discontinued. Any suspected lethal exposure must be reported immediately to Celgene Customer Care Center at 1-888-423-5346, and the patient referred to an OB/GYN experienced in reproductive toxicity for further evaluation and counseling.

  • Patient (or legally authorized representative) must be able to understand and willing to sign a written informed consent document.

Exclusion Criteria:

  • 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.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Experimental

Arm Label

Control

Metronomic Cyclophosphamide

Thalidomide

Arm Description

No intervention

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

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

Outcomes

Primary Outcome Measures

Safety as measured by absence of grade 4 or 5 non-hematological or grade 5 hematological toxicity
Incidence of major transplant related toxicities (Grades IV and IV)

Secondary Outcome Measures

Best overall response
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1.

Full Information

First Posted
July 30, 2012
Last Updated
January 29, 2023
Sponsor
Washington University School of Medicine
search

1. Study Identification

Unique Protocol Identification Number
NCT01661400
Brief Title
Anti-Angiogenic Therapy Post Transplant (ASCR) for Pediatric Solid Tumors
Acronym
ASCR
Official Title
Anti-Angiogenic Therapy After Autologous Stem Cell Rescue (ASCR) for Pediatric Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 26, 2012 (Actual)
Primary Completion Date
December 27, 2023 (Anticipated)
Study Completion Date
December 27, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma, Neuroectodermal Tumors, Primitive, Wilms Tumor, Rhabdomyosarcoma, Sarcoma, Ewing, Osteosarcoma, Retinoblastoma
Keywords
Glioma includes ependymoma and medulloblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
No Intervention
Arm Description
No intervention
Arm Title
Metronomic Cyclophosphamide
Arm Type
Experimental
Arm Description
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
Arm Title
Thalidomide
Arm Type
Experimental
Arm Description
Thalidomide will be initiated at 3mg/kg PO daily beginning Day + 30 (30 days post transplant) and continue until Day +86
Intervention Type
Drug
Intervention Name(s)
Metronomic Cyclophosphamide
Other Intervention Name(s)
Cytoxan®, CPM
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Other Intervention Name(s)
Thalomid®
Primary Outcome Measure Information:
Title
Safety as measured by absence of grade 4 or 5 non-hematological or grade 5 hematological toxicity
Time Frame
Through 1 year post-transplant
Title
Incidence of major transplant related toxicities (Grades IV and IV)
Time Frame
Within the first year of transplant
Secondary Outcome Measure Information:
Title
Best overall response
Description
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1.
Time Frame
86 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Ejection fraction of ≥ 50% by radionuclide angiogram Patient must have adequate pulmonary function tested within 4 weeks of study enrollment as defined by: Pulse oximetry > 94% on room air or O2 by nasal cannula and No evidence of dyspnea at rest. Patient must have adequate hepatic function as defined by: Total bilirubin ≤ 1.5x upper limit of normal (ULN) for age and SGOT (AST) or SGPT (ALT) ≤ 2.5 x ULN (SGOT ≤ 4x ULN if on Zantac) Patient must have adequate renal function as defined by: Serum creatinine < 1.5 mg/dl Glomerular filtration rate (GFR), calculated via I-125 iothalamate clearance, 24-hour creatinine clearance, or Schwartz formula*, ≥ 70 mL/min and ≥ 50 mL/min/1.73 m2 done within 4 weeks of study entry The Schwartz formula is an estimated glomerular filtration rate in children based upon serum creatinine and height. Height (Ht) should be measured in cm and serum creatinine (Cr) in mg/dL. Proportionality constant (k) is 0.55 for children and adolescent girls and 0.7 for adolescent boys aged 13-21. This constant is based upon a series of evaluations performed by Schwartz. Formula: GFR= (k x Ht)/Cr Enrollment in the Celgene THALOMID REMSTM Program: If enrolled in Arm III of this study, patient must be registered at the Celgene THALOMID REMSTM Program prior to day +30 post-ASCR. If enrolled in Arm III of this study, patient must be willing to practice birth control as outlined in the THALOMID REMSTM Program from the beginning of the thalidomide treatment until at least 4 weeks following discontinuation of thalidomide therapy. Two reliable forms of contraception must be used simultaneously unless continuous abstinence from heterosexual sexual contact is chosen. Contraceptive methods must include at least one highly effective method (e.g. oral contraceptive pills, injections, hormonal patches, IUD, or implants), AND one additional effective barrier method (e.g. latex condom, diaphragm, cervical cap). If hormonal or IUD contraception is medically contraindicated, another highly effective method or two barrier methods must be used at the same time. Pregnancy surveillance: i. Patient must have a negative in office pregnancy test sensitive to within 50 mIU/mL (serum or urine) within 24 hours prior to beginning thalidomide even if continuous abstinence is the preferred method of birth control. ii. A pregnancy test must be performed weekly during the first 4 weeks of therapy and repeated monthly for patients with regular menses or every 2 weeks for patients with irregular menses iii. Negative pregnancy tests are valid for only 7 days. iv. If irregular bleeding or skipped menses, pregnancy test should be performed and pregnancy counseling given. v. If pregnancy occurs during treatment, thalidomide must be immediately discontinued. Any suspected lethal exposure must be reported immediately to Celgene Customer Care Center at 1-888-423-5346, and the patient referred to an OB/GYN experienced in reproductive toxicity for further evaluation and counseling. Patient (or legally authorized representative) must be able to understand and willing to sign a written informed consent document. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Cluster, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

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

We'll reach out to this number within 24 hrs