Clinical Trial VICCPED0801
Phase I Feasibility Study of Clofarabine and Low Dose Total Body Irradiation (TBI) as a Non-myeloablative Preparative Regimen for Stem Cell Transplantation (SCT) for Hematologic Malignancies: a Multi-Center Study
- Protocol No. VICCPED0801
- Open Date: 06/06/2008
- Staging: Phase I
- Age Group: Children
- Scope: Local
- Objective: To determine the maximum feasible dose (MFD) of Clofarabine that can be administered in combination with 2Gy total body irradiation (TBI) as a non-myeloablative preparative regimen for allogeneic Stem Cell Transplantation (SCT) in pediatric patients with advanced hematological malignancies.
- Disease Sites: Pediatrics; Leukemia
- Therapies: Chemotherapy - cytotoxic; Radiotherapy
- Drugs: Clofarabine
- Participating Institutions: Vanderbilt University; Hackensack University Medical Center
- National Clinical Trial ID: NCT01041508
- Secondary Protocol No: TACL 2008-005
Patients are being asked to take part in this research study because they have advanced cancer of the blood. Patients with this cancer are going to have a stem cell transplant to treat the disease. Patients would have needed the stem cell transplant even if they were not taking part in this study. Stem cells are -seed cells- needed to make blood cells. Transplantation of blood stem cells is the only way to treat some diseases. Before the transplant, a patient must have -conditioning therapy- to prepare the body for the transplant. The aims of conditioning therapy are: - To kill cancer cells in the body - To kill normal cells in the bone marrow so that new marrow from the donor will have room to grow - To suppress the immune system so it won-t reject the donor cells During this study, a drug called Clofarabine will be given before the stem cell transplant. Clofarabine is approved by the Food and Drug Administration (FDA) to treat children, ages 1 to 21, who have a type of leukemia called relapsed or refractory acute lymphoblastic leukemia (ALL), only after at least 2 other types of treatment have failed. ALL is a cancer of the white blood cells. White blood cells fight infection in the body. Clofarabine is not approved by the FDA as a conditioning regimen for transplant and is also not approved at the dose level used in this study. The patient will also be given low-dose total body radiation to help their body accept the donor stem cells. The doses of Clofarabine and radiation given in this study are not strong enough to destroy the immune system so patients will be given drugs after the transplant to help the body accept the donor stem cells and prevent GVHD (graft versus host disease). GVHD is a problem that can happen after any type of transplant. It is caused by certain donor cells that attack parts of your body.
|Ages Eligible for Study:||1 Year to 21 Years|
|Genders Eligible for Study:||Both|
|Accepts Healthy Volunteers:||No|
• Patients must be greater than or equal to 1 and less than or equal to 21 years of age at the of study entry.
• Patients must have a diagnosis of ALL or AML.
• ALL patients must be in clinical remission defined as BM morphology <5% blasts and CNS 1 status.
• AML patients must be in M1 (<5% blasts) or M2 (<20% blasts) marrow status with CNS 1 status.
• Patient must have an ANC greater than or equal to 750/ul.
• Patient must have one of the appropriate donor types as described below:
1. HLA identical sibling donor.
2. Complete matched unrelated donor, (matched at A, B, C, DR B1 and DQ, B1 at the allelic level based on high resolution typing for Class I and II antigens, 10/10 match).
3. 1 allelic mis-matched unrelated donor (antigen mis-matches are not allowed).
• The stem cell source from the donor must be one of the following:
1. Bone Marrow or Peripheral blood stem cells (PBSC) from a matched related donor.
2. PBSC from an unrelated donor. (Bone marrow is not acceptable for unrelated donors)
• Karnofsky > 50% for patients > 10 years of age and Lansky > 50% for patients less than or equal to 10 years of age.
• Female patients of childbearing potential must have a negative serum pregnancy test confirmed within 2 weeks prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this study.
• Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study.
• Patients must have a calculated creatinine clearance ≥ 70mL/min/m2 as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1.73 m2) = k * Height (cm)/serum creatinine (mg/dl). K is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 adolescent boys.
• Total serum bilirubin < 2 mg/dL.
• Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 5 × ULN.
• Patient must have a shortening fraction (SF) > 25%. If the SF is <25%, patient must have an ejection fraction (EF) by MUGA of >30%.
• Patient must have pulmonary function as defined below:
1. DLCO >30%
2. FVC/TLC >30%
3. FEV1 > 30% of predicted
4. Patient is not on continuous oxygen If patient is not old enough or unable to comply with pulmonary function tests, they must have a pulse ox >92% in room air and not be on continuous oxygen.
• Patient must have signed informed consent
• Patients will be excluded if they have evidence of an active, progressive invasive infection. All patients with existing infections at the time study entry should be discussed with the study chair.
• Patients may have stable invasive infections and still be eligible.
• Patients with infections that are responsive to medical or surgical treatment as shown by radiographic and or microbial assessment may still be eligible.
• Patients will be excluded if they have an active, uncontrolled systemic fungal, bacterial, viral or other infection. All patients with existing infections at the time of study entry should be discussed with the study chair.
•An active uncontrolled infection is defined as exhibiting ongoing signs and symptoms related to the infection (fevers, positive blood cultures, chills, tachycardia, etc) despite appropriate antibiotics or other treatment.
• Patient has a diagnosis of CML or MDS.
• Patient has CNS 2 or CNS 3 status.
• Patient is HIV positive.
• Current or planned treatment with chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry.
• Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney (including dialysis patients), liver, or other organ system that may place the patient at undue risk to undergo treatment.
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, study participation, follow up, or interpretation of study results.