Decitabine, Doxorubicin, and Cyclophosphamide in Treating Children With Relapsed or Refractory Solid Tumors or Neuroblastoma

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase I trial is studying the side effects and best dose of decitabine when given together with doxorubicin and cyclophosphamide in treating children with relapsed or refractory solid tumors or neuroblastoma. Drugs used in chemotherapy, such as decitabine, doxorubicin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Azacitidine; Cyclophosphamide; Decitabine; Doxorubicin; Lenograstim; Liposomal doxorubicin

Criteria

Inclusion Criteria:

• Histologically confirmed diagnosis of either of the following:

• Solid tumor (part A)

• No lymphoma

• Neuroblastoma (part B)

• Original diagnosis may be based on elevated urine vanillylmandelic acid (VMA) and homovanillic acid (HVA) and bone marrow examination

• Accessible disease by bone marrow aspirate or tumor biopsy

• No laparotomy, thoracotomy, endoscopy, or craniotomy for biopsy

• No known curative therapy OR therapy proven to prolong survival with an acceptable quality of life available

• No known brain or spinal cord metastases

• No CNS tumors

• Performance status - Karnofsky 50-100% (patients 11 to 21 years of age)

• Performance status - Lansky 50-100% (patients ≤ 10 years of age)

• Parts A and B without bone marrow infiltration:

• Absolute neutrophil count ≥ 1,000/mm^3

• Platelet count ≥ 100,000/mm^3 (transfusion independent)

• Part B with bone marrow infiltration (i.e., tumor metastatic to bone marrow with granulocytopenia, anemia, and/or thrombocytopenia):

• Absolute neutrophil count ≥ 750/mm^3

• Platelet count ≥ 50,000/mm^3 (transfusion independent)

• Hemoglobin ≥ 8.0 g/dL (transfusion allowed)

• No sickle cell anemia

• Bilirubin ≤ 1.5 mg/dL

• ALT ≤ 5 times upper limit of normal

• No significant hepatic dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results

• Creatinine based on age as follows:

• ≤ 0.8 mg/dL (5 years of age and under)

• ≤ 1.0 mg/dL (6 to 10 years of age)

• ≤ 1.2 mg/dL (11 to 15 years of age)

• ≤ 1.5 mg/dL (16 to 21 years of age)

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min

• No significant renal dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results

• Shortening fraction ≥ 28% by echocardiogram

• Ejection fraction of ≥ 45% by MUGA

• No significant pulmonary dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No prior allergic reaction attributed to compounds of similar chemical or biological composition to agents used in this study

• No uncontrolled serious infection

• No significant end-organ dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results

• Recovered from prior immunotherapy

• At least 7 days since prior biologic therapy

• More than 1 week since prior growth factor therapy (2 weeks for pegfilgrastim)

• More than 2 weeks since prior epoetin alfa

• At least 6 months since prior autologous stem cell transplantation

• At least 6 months since prior allogeneic bone marrow transplantation

• Patients must have full organ recovery and no evidence of graft-versus-host disease

• No concurrent immunomodulating agents

• No concurrent immunotherapy

• No concurrent biologic therapy

• No concurrent epoetin alfa

• Recovered from prior chemotherapy

• More than 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)

• Prior total lifetime cumulative anthracycline dose ≤ 450 mg/m^2 of doxorubicin or equivalent

• No other concurrent chemotherapy

• No concurrent hydroxyurea

• Recovered from prior radiotherapy

• More than 2 weeks since prior local palliative small port radiotherapy

• More than 6 months since prior substantial bone marrow irradiation (e.g., cranio-spinal irradiation, total body irradiation, or hemi-pelvic irradiation)

• No concurrent radiotherapy

• No other concurrent anticancer therapy

• No other concurrent investigational agents

• Concurrent oral iron supplementation for patients with a known iron deficiency or a microcytic hypochromic anemia allowed