Treatment of High Risk Adult Acute Lymphoblastic Leukemia (LAL-AR/2003)

Tracking Information
First Submitted Date ICMJE	February 25, 2009
First Posted Date ICMJE	February 27, 2009
Last Update Posted Date	January 11, 2018
Study Start Date ICMJE	January 2003
Estimated Primary Completion Date	December 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 26, 2009)	To evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels in HR Ph- adult ALL patients. [ Time Frame: 2 years ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00853008 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Treatment of High Risk Adult Acute Lymphoblastic Leukemia
Official Title ICMJE	Treatment of High Risk Adult Acute Lymphoblastic Leukemia
Brief Summary	Current therapeutic protocols for adult ALL consider MRD together with the baseline risk factors (age, WBC count, immunophenotype, cytogenetics) and speed in response to therapy for treatment decisions. On the other hand, the systematic use of allogeneic SCT for all adult patients (pts) with Ph- HR-ALL is still a matter of debate. The aim of the prospective study ALL-AR-03 from the Spanish PETHEMA Group was to evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels (assessed by cytofluorometry at the end of induction and consolidation therapy) in HR Ph- adult ALL patients.
Detailed Description	HR ALL included one or more of the following baseline parameters: age 30-60 yr, WBC count >25x109/L and 11q23 or MLL rearrangements. Induction therapy included vincristine, prednisone and daunorubicin for 4 weeks. In pts with slow cytologic response to therapy (≥10% blasts in bone marrow assessed on d14) intensified induction with high dose ARA-C and mitoxantrone was administered. Early consolidation therapy included 3 cycles with rotating cytotoxic drugs including high-dose methotrexate, high-dose ARA-C and high-dose asparaginase. Pts. with slow cytologic response on d14 or MRD level >0.05% after consolidation were assigned to allogeneic SCT (related or unrelated) and those with standard cytologic response on d14 and MRD level <0.05% after consolidation received 3 additional cycles of delayed consolidation (identical to those of early consolidation) followed by maintenance therapy up to 2yr in CR.
Study Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Acute Lymphoblastic Leukemia
Intervention ICMJE	Drug: Vincristine Vincristine (VCR): 1.5 mg/m2 (max 2 mg) IV d 1, 8, 15, 22 in induction VCR 2 mg, IV, d 1,8 in consolidation (cycle 1, 2); Drug: Daunorubicin Daunorubicin (DNR): 60 mg/m2 IV d 1, 8, 15, 22; Drug: Prednisone Prednisone (PDN): 60 mg/m2/d IV or PO, d 1-28; Drug: Mitoxantrone Mitoxantrone:12 mg/m2, IV d 15-17 in induction 12 mg/m2, IV,d 5 in cycle 2 consolidation; Drug: Cytosine Arabinoside ARA-C 2,000 mg/m2/12h IV, d18,19 (4 doses) in induction; Drug: Dexamethasone Dexamethasone 20 mg/m2,IV, d 1-5,10 mg/m2,IV, d 6 and 5 mg/m2,IV, d 7 in Consolidation (3 cycles); Drug: Methotrexate (MTX) Methotrexate (MTX)3 g/m2,IV, d1 (24h)in consolidation, cycles 1 and 2 MTX (15 mg/m2/wk, IM)in maintenance MTX 15 mg, IT; Drug: Cytarabine Cytarabine 2g/m2/12h, IV d5 in cycle 1 consolidation Cytarabine 2g/m2/12h, IV d 1,2 in cycle 3 consolidation Cytarabine 30 mg, intrathecal; Drug: ASP ASP 25,000 IU/m2, IV, d5 in consolidation (cycle 1, 2, 3); Drug: Mercaptopurine Mercaptopurine 100 mg/m2, PO, d 1-5 in consolidation; Drug: Teniposide Teniposide 150 mg/m2, IV d 3,4 in consolidation cycle 3; Drug: Hydrocortisone Hydrocortisone 20 mg, IT d 1, 28, 49, 77, 105, 175, 203, 231, 259,287, 311 intrathecal
Study Arms	Not Provided
Publications *	Ribera JM, Oriol A, Morgades M, Montesinos P, Sarrà J, González-Campos J, Brunet S, Tormo M, Fernández-Abellán P, Guàrdia R, Bernal MT, Esteve J, Barba P, Moreno MJ, Bermúdez A, Cladera A, Escoda L, García-Boyero R, Del Potro E, Bergua J, Amigo ML, Grande C, Rabuñal MJ, Hernández-Rivas JM, Feliu E. Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. J Clin Oncol. 2014 May 20;32(15):1595-604. doi: 10.1200/JCO.2013.52.2425. Epub 2014 Apr 21.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Estimated Enrollment ICMJE; (submitted: February 26, 2009)	100
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	January 2019
Estimated Primary Completion Date	December 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: High risk ALL adult patients (age> 15 years)no treated previously; High-risk ALL:; One or more of the following: Age 30-60 yr. WBC count >25x109/L 11q23 or ALL1/AF4; Very high-risk ALL:; HR ALL and one or the following: Slow cytologic response (>10% blasts in BM on d14 of induction therapy). MRD>0.05% (by flow cytometry) at the end of consolidation Exclusion Criteria: L3 ALL or B mature(sIg +) or t(8;14), t(2;8), t(8;22).; ALL Ph (BCR/ABL) positive.; Bifenotipics ALL as EGIL criteria.; Indifferentiated ALL.; Patients with cardiac pathology; Patients with chronic liver disease in activity fase; Pulmonary disease; Renal insufficiency not due to ALL; Neurological disorders not due to ALL; PS (grades 3 and 4) not due to ALL.
Sex/Gender	Sexes Eligible for Study: All
Ages	16 Years and older (Child, Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Spain
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00853008
Other Study ID Numbers ICMJE	LAL-AR/2003
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	PETHEMA Foundation
Study Sponsor ICMJE	PETHEMA Foundation
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Chair: Ribera Josep Mª, Dr PETHEMA Foundation
PRS Account	PETHEMA Foundation
Verification Date	January 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP