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

• ClinicalTrials.gov Identifier: NCT00853008
• Recruitment Status: Completed
• First Posted: February 27, 2009
• Last Update Posted: April 7, 2020
• Sponsor: PETHEMA Foundation
• Information provided by (Responsible Party): PETHEMA Foundation

Tracking Information

• First Submitted Date: February 25, 2009
• First Posted Date: February 27, 2009
• Last Update Posted Date: April 7, 2020
• Study Start Date: January 2003
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (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: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Treatment of High Risk Adult Acute Lymphoblastic Leukemia
• Official Title: 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: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Lymphoblastic Leukemia

Intervention

• 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.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: February 26, 2009): 100
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2012
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT00853008
• Other Study ID Numbers: 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: PETHEMA Foundation
• Collaborators: Not Provided

Investigators

• Study Chair: Ribera Josep Mª, Dr; PETHEMA Foundation

• PRS Account: PETHEMA Foundation
• Verification Date: April 2020