Cyclophosphamide or Thalidomide after Stem Cell Transplant in Treating Younger Patients with Solid Tumors

Status: Active

Description

This early phase I pilot clinical trial studies cyclophosphamide or thalidomide following high dose chemotherapy and stem cell transplant in treating younger patients with solid tumors. Drugs such as cyclophosphamide and thalidomide suppress the growth of new blood vessels to tumors. Blocking blood flow to tumors after receiving high dose chemotherapy and a stem cell transplant may prevent the tumors from coming back or continuing to grow.

Eligibility Criteria

Inclusion Criteria

  • Patient must have an original diagnosis, benefited by autologous transplantation, confirmed by biopsy* of solid tumor, including but not limited to: 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 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 cluster of differentiation (CD)34+ 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
  • Hemoglobin >= 8.0 g/dl
  • Peripheral absolute neutrophil count (ANC) >= 750/mm^3
  • Shortening fraction of >= 27% by echocardiogram (within 4 weeks prior to study enrollment) OR
  • Ejection fraction of >= 50% by radionuclide angiogram (within 4 weeks prior to study enrollment)
  • Pulse oximetry > 94% on room air or oxygen (O2) by nasal cannula (within 4 weeks prior to study enrollment)
  • No evidence of dyspnea at rest (within 4 weeks prior to study enrollment)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x ULN (SGOT =< 4 x ULN if on Zantac)
  • 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 or >= 50 mL/min/1.73 m^2 done within 4 weeks prior to study entry
  • Enrollment in the Celgene THALOMID REMS Program: * If enrolled in Arm III of this study, patient must be registered at the Celgene THALOMID REMS Program * If enrolled in Arm III of this study, patient must be willing to practice birth control as outlined in the THALOMID REMS Program from the beginning of the study 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, intrauterine device [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: ** Patient must have a negative in office pregnancy test sensitive to within 50 mIU/mL (serum or urine) within 24 hours of beginning thalidomide even if continuous abstinence is the preferred method of birth control ** 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 ** Negative pregnancy tests are valid for only 7 days ** If irregular bleeding or skipped menses, pregnancy test should be performed and pregnancy counseling given ** 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 obstetrician (OB)/gynecologist (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 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version (v)4.0 (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

Locations & Contacts

Missouri

Saint Louis
Saint Louis Children's Hospital
Status: Active
Contact: Andrew Stephen Cluster
Phone: 314-454-6018
Email: acluster@wustl.edu
Siteman Cancer Center at Washington University
Status: Active
Contact: Andrew Stephen Cluster
Phone: 314-454-6018
Email: acluster@wustl.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the feasibility and safety of administering anti-angiogenic therapy following high-dose chemotherapy and autologous stem cell rescue in pediatric patients with solid tumors.

II. To determine major transplant related toxicities (grades IV and V) within the first year post transplant.

SECONDARY OBJECTIVES:

I. To measure the overall response to anti-angiogenic therapy following high-dose chemotherapy and autologous stem cell rescue in pediatric patients with solid tumors.

II. To assess the utility of a radiographic marker of neovascularization as measurement of anti-angiogenic activity in the treatment of solid tumors, with assessments before and after treatment: To determine if the use of anti-angiogenic therapy can result in anti-vascular and vascular normalization effects on tumors by magnetic resonance imaging (MRI) before and, in the case of patients with residual tumor, following treatment.

III. To explore if there is a correlation between previously identified single nucleotide polymorphisms (SNPs) and response and outcome of patients receiving thalidomide.

OUTLINE: Patients are assigned to 1 of 3 treatment arms.

ARM I: (closed to accrual 1/23/14)

PREPARATIVE REGIMEN: Patients receive carboplatin intravenously (IV) over 1 hour on days -8 to -6, etoposide IV over 3 hours on days -5 to -3, and thiotepa IV over 2 hours on days -5 to -3.

TRANSPLANT: Patients undergo autologous peripheral blood stem cell (PBSC) or bone marrow (BM) transplant on day 0.

FILGRASTIM THERAPY: Patients receive filgrastim subcutaneously (SC) or IV over 15-30 minutes beginning 24 hours after transplant and continuing until absolute neutrophil count (ANC) recovers.

ARM II: Patients receive preparative regimen, transplant, and filgrastim therapy as in Arm I and receive cyclophosphamide orally (PO) once daily (QD) on days 30-86.

ARM III: Patients receive preparative regimen, transplant, and filgrastim as in Arm I and receive thalidomide PO daily on days 30-86.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Saint Louis Children's Hospital

Principal Investigator
Andrew Stephen Cluster

Trial IDs

Primary ID 201209088
Secondary IDs NCI-2012-01541
Clinicaltrials.gov ID NCT01661400