Trial Title:
Autologous Hematopoietic Cell Transplantation for Core-binding Factor (CBF) Acute Myeloid Leukemia (AML) in the First Complete Remission (CR1)
NCT ID:
NCT01146977
Condition:
Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cytarabine
Conditions: Keywords:
CBF(+)
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Unknown status
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
HDAC chemotherapy
Description:
If he/she decides not to participate, he/she will be treated with HDAC consolidation
chemotherapy, which is the current standard treatment.
Arm group label:
HDAC chemotherapy
Other name:
Cytarabine 3g/m2
Intervention type:
Other
Intervention name:
Autologous HCT
Description:
After achieving CR1, patient will be invited to this protocol and will be able to decide
whether to join or not after listening to the information.
If he/she decides to participate, request of health insurance support on the autologous
HCT will be submitted and further processes related to autologous HCT will continue.
Arm group label:
Autologous HCT
Summary:
Evaluation of efficacy of autologous hematopoietic cell transplantation (HCT) with
core-binding factor (CBF) positive acute myeloid leukemia (AML) in the first CR (CR1).
Detailed description:
5.2 AUTOLOGOUS PBSCS HARVESTING
5.2.1. PBSCs will be collected during recovery phase after the second cycle of HDAC
consolidation chemotherapy.
5.2.2. For mobilization, recombinant human granulocyte- colony-stimulating factor (G-CSF,
Filgrastim) will be given subcutaneously at a dose of 10 mcg/kg from day 9 of the 2nd
HDAC cycle until the completion of harvesting.
5.2.3. PBSCs harvesting will be performed via perm-cath or Quinton catheter, which will
be inserted with fluoroscopy-guided before starting and will be removed after finishing
harvest.
5.2.4. Harvest will be initiated from the day when the peripheral absolute neutrophil
count reach up to 0.2 x 109/mm3. Peripheral blood mononuclear cells will be collected by
leukapheresis method with 'CS-3000' (Baxter, Deerfield, IL) or other compatible machine.
Cell collection will be performed for at least 2 days and the duration of collection can
be extended until a target CD34+ cell dose of 5 x 106/kg (in terms of body weight of
recipient) is collected.
5.2.5. If adequate numbers of CD34+ cells are not collected, the 3rd HDAC chemotherapy
will be done and mobilization/harvest procedure will be repeated.
5.2.6. Stem cells harvested from patient will be frozen in liquid nitrogen tank for
future autologous HCT cell infusion.
5.3.PRETRANSPLANT WORKUP FOR AUTOLOGOUS HCT 5.3.1. Pre-workup for checking the current
disease status and feasibility for autologous HCT will be performed before the
conditioning and infusion of autologous HCT.
5.3.2. It is recommended that baseline workup for hematologic / non-hematologic status
will be performed at least 1 month prior to the initiation of conditioning. Bone marrow
aspirate/ biopsy with cytogenetics and diagnostic lumbar puncture can be performed
immediately before the initiation of conditioning.
5.3.3. Pretransplant workup tests are listed in Appendix IV.
5.4. CONDITIONING REGIMEN FOR AUTOLOGOUS HCT 5.4.1. On admission, 5.4.1.1.Menstruating
women will be given norethindrone (Norlutate) 10mg po daily until platelet count is
consistently over 100,000 /mcL.
5.4.1.2.Actual body weight (ABW) for busulfan will be calculated using following
guidelines; 5.4.1.2.1.If ABW is less or equal to ideal body weight (IBW), use ABW.
5.4.1.2.2.If ABW is greater than IBW but ABW is within 120% of IBW, use IBW. 5.4.1.2.3.If
ABW is 120% or greater than IBW, use IBW+25% (ABW-IBW). 5.4.1.2.4.IBW(ideal body weight)
will be calculated in 5.4.1.2.4.1.Male: 50 kg + 2.3kg (height[inch]-60)
5.4.1.2.4.2.Female: 45.5kg + 2.3kg (height[inch]-60) 5.4.1.2.4.3.1inch=2.54cm 5.4.2. On
day -8, preparation drugs will be administered to patient as below; 5.4.2.1.Hydration
with 0.9% normal saline will be started at 6PM and infused continuously at a rate of
100mL/hr through day -4.
5.4.2.2.Allopurinol 300mg/day will be taken p.o. once a day from day-8 to -2.
5.4.2.3.Heparin 100 U/kg/day in normal saline 500 mL will be infused continuously at a
rate of 20mL/hr through day 20 (6pm). Heparin should be discontinued if there is
clinically significant bleeding or aPTT level exceeds 1.2 time of the upper normal limit.
5.4.2.4.Dilantin 15mg/kg (ABW) in normal saline 300cc will be infused continuously at a
rate of 200mL/hr at 8PM, and then, 200mg will be taken p.o. twice a day through day -4.
Dilantin level should be monitored in the morning of day-7 and -6 to maintain the level
within 10 to 20 mg/L.
5.4.3. From day-7, conditioning drug will be administered to patient as below;
5.4.3.1.Busulfan 3.2mg/kg/day in normal saline of 10 times the volume of busulfan will be
infused continuously over 3 hours with an interval of 24 hours on days -7 to -5 (for 3
days).
5.4.3.2.Etoposide 200mg/m2/day in normal saline 1000mL will be infused continuously over
5 hours twice a day with an interval of 12 hours on day-3 to -2 (for 2 days).
5.4.3.3.Antiemetics such as serotonin antagonist or lorazepam are allowed.
5.5. AUTOLOGOUS PBSCS INFUSION 5.5.1. Autologous PBSCs will be infused on day0.
5.5.1.1.Premedication including pheniramine maleate (avil) 45.5mg i.v., acetaminophen
600mg p.o., hydrocortisone 250mg i.v. and furosemide 20mg i.v. will be given 30 minutes
before cell infusion.
5.5.1.2.PBSCs will be infused via saline infusion set without in-line filters.
5.5.1.3.Vital sign should be checked 4 times with 15 minutes of interval, 4 times with 30
minutes, and then 4 times with 1 hour. Electrocardiogram monitoring will be performed
from the start until the completion of PBSCs infusion.
5.5.1.4.Following medications should not be administered simultaneously with PBSCs;
5.5.1.4.1.Lipid-containing total parenteral nutrition fluid 5.5.1.4.2.Conventional or
liposomal amphotericin 5.6. SUPPORTIVE CARE 5.6.1. Recombinant human G-CSF (rhG-CSF) 450㎍
in 100 mL of D5W will be infused intravenously over 30 minutes from day 5 till
ANC>3,000/㎕.
5.6.2. Ciprofloxacin 500mg will be given p.o. twice a day (for selective bowel
decontamination) from day 1 till ANC>3,000/㎕. With the first fever spike, ciprofloxacin
can be replaced with broad spectrum antibiotics.
5.6.3. Micafungin 50mg will be infused intravenously once a day from day1 till
ANC>3,000/㎕.
5.6.4. Acyclovir 250mg/m2 will be infused twice a day from day1 till ANC>3,000/㎕.
5.6.5. In case of oral mucositis, sodium bicarbonate/saline mouthwash will be applied
four times a day until resolved.
5.6.6. Clotrimazole or Canesten® powder can be applied to groin, axilla, and perianal
area twice a day from day-8 until engraftment.
5.6.7. All cellular blood products must be transfused after leukocyte filtration and
irradiation.
5.6.8. For woman of childbearing potential, adequate consultation for ovarian protection
can be sought. For man who intend to have child(ren) in future, sperm banking can be
recommended and performed.
5.7. EVALUATION DURING TREATMENT 5.7.1. CBC with differential count, ALT/AST, bilirubin
with BUN/Cr, and electrolyte will be checked once daily.
5.7.2. Chemical battery with BUN/phosphorus, LDH and level of magnesium will be checked
three times a week.
5.7.3. Coagulation battery with fibrinogen/d-dimer will be checked at day 0, 7, 14, 21
and once a week thereafter until discharge.
5.7.4. Protein C, antithrombin III, t-PA antigen, and PAI-1 antigen will be checked at
day 0, 7, 14, and 21.
5.7.5. Urinalysis will be checked once a week. 5.7.6. Chest X-ray will be checked once a
week routinely and more frequently according to patient's condition.
5.7.7. Blood galactomannan (aspergillosis antigen, GM) assay can be recommended to be
checked once a week until ANC>3,000/ according to the physician's decision.
5.8. POST-HCT FOLLOW-UP INCLUDING MRD MONITORING 5.8.1. Patients will be followed with
physical examination and appropriate blood test including CBC at least every 3 months for
3 years, every 6 months for the next 2 years, and then annually thereafter.
5.8.2. Toxicities related to treatment will be assessed and reported according to NCI
CTCAE v3.0.
5.8.3. Minimal residual disease (MRD) monitoring with RQ-PCR for AML1/ETO or CBFβ/MYH11
will be performed before autologous HCT (bone marrow and peripheral blood, 1 month after
autologous HCT (bone marrow and peripheral blood), and thereafter, every 3 months
(peripheral blood only) until 3 years after autologous HCT.
5.8.4. If RQ-PCR is not available, RT-PCR and/or FISH can be used for MRD monitoring
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with CBF positive AML in CR1. CBF AML includes t(8;21)(q22;q22)
[AML1(RUNX1)/ETO(CBFα2T1)], inv(16)(q13q22) (CBFβ/MYH11),t(16;16)(p13;q22)
(CBFβ/MYH11) Using RT-PCR, FISH, or standard karyotype analysis technique.
- Patients who plan to receive the second cycle of HDAC consolidation chemotherapy.
- 15 years old or older and 65 years or younger
- Adequate performance status (Karnofsky score of 70 or more).
- Adequate hepatic and renal function (AST, ALT, and bilirubin < 3.0 x upper normal
limit, and creatinine < 2.0 mg/dL).
- Adequate cardiac function (left ventricular ejection fraction over 40% on heart scan
or echocardiography)
- Signed and dated informed consent must be obtained from patient.
Exclusion Criteria:
- Presence of significant active infection
- Presence of uncontrolled bleeding
- Any coexisting major illness or organ failure
- Patients with psychiatric disorder or mental deficiency severe as to make compliance
with the treatment unlike, and making informed consent impossible
- Nursing women, pregnant women, women of childbearing potential who do not want
adequate contraception
- Patients with a diagnosis of prior malignancy unless disease-free for at least 5
years following therapy with curative intent (except curatively treated nonmelanoma
skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)
Gender:
All
Minimum age:
15 Years
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Asan Medical Center
Address:
City:
Seoul
Zip:
138-736
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Yae Eun Jang, nurse
Phone:
82-2-3010-6378
Email:
redpin75@paran.com
Start date:
January 2010
Completion date:
December 2015
Lead sponsor:
Agency:
Cooperative Study Group A for Hematology
Agency class:
Other
Source:
Cooperative Study Group A for Hematology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01146977
http://www.google.co.kr
