LAL0904: Chemotherapy With or Without Imatinib and/or Peripheral Stem Cell Transplant in Acute Lymphoblastic Leukemia

• Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto (Other)
• Overall Status: Completed
• CT.gov ID: NCT00458848
• Collaborator: (none)
• Enrollment: 470
• Locations: 66
• Duration (Months): 113
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. When the healthy stem cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving combination chemotherapy together with imatinib mesylate and peripheral stem cell transplant may be an effective treatment for acute lymphoblastic leukemia.

Nevertheless, in the last few years GIMEMA has pubblished a paper in which 100% of Ph+ ALL patients reach HCR only with Imatinib, without any chemiotherapy. Thus, this treatment will be implemented in patients pertaining to this category.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: asparaginase; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: idarubicin; Drug: imatinib mesylate; Drug: mercaptopurine; Drug: methotrexate; Drug: methylprednisolone; Drug: mitoxantrone hydrochloride; Drug: prednisone; Drug: vincristine sulfate; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: autologous hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 470 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Adult Acute Lymphoblastic Leukaemia (ALL): Imatinib in Combination With Chemotherapy in Ph+ Patients, and Post-remissional Treatment Intensification in High-risk Ph- Patients, With Minimal Residual Disease Monitoring.
• Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Reaching Disease Free Survival [At 60 months]

Secondary Outcome Measures

1. Number of Patients Reaching Complete Hematological Response After Induction Therapy [At the end of induction, day +50]

2. Percentage of Participants Reaching Overall Survival [At 60 months]

   Overall survival from diagnosis

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of acute lymphoblastic leukemia (ALL) meeting the following criteria:

• Negative myeloperoxidase stain

• Phenotype T (T-ALL) or B (B-ALL)

• No mature B-ALL (FAB L3, serum immunoglobulin-positive, terminal deoxynucleotidyl transferase-negative)

PATIENT CHARACTERISTICS:

• Creatinine ≤ 2.5 mg/dL (after adequate hydration)

• SGOT and SGPT ≤ 3 times upper limit of normal

• LVEF ≥ 50%

• No severe psychiatric disorders

• No other concurrent malignant disease

• No presence of documented infections not responding to antibiotic and/or antifungal therapy

• Not pregnant

PRIOR CONCURRENT THERAPY:

• No prior steroids

• No prior antiblastic chemotherapy

• No other concurrent chemotherapy or radiotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ospedale Civile Alessandria	Alessandria		Italy	I-15100
2	Ospedale Torrette University Ancona	Ancona		Italy	60020
3	Ospedale S. Donato	Arezzo		Italy	52100
4	Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"	Ascoli Piceno		Italy
5	S.G. Moscati Hospital	Avellino		Italy	83100
6	Universita Degli Studi di Bari	Bari		Italy	70124
7	University of Bologna Medical School	Bologna		Italy	40138
8	Spedali Civili di Brescia	Brescia		Italy	25123
9	A. Perrino Hospital	Brindisi		Italy	72100
10	Ospedale Binaghi	Cagliari		Italy	090100
11	Ospedale Ferrarotto	Catania		Italy	95124
12	Ospedale Regionale A. Pugliese	Catanzaro		Italy	88100
13	U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza	Cosenza		Italy
14	Universita di Ferrara	Ferrara		Italy	44100
15	Azienda Ospedaliera di Firenze	Florence		Italy	50011
16	Ospedali Riuniti Foggia	Foggia		Italy	71100
17	Ospedale Umberto I	Frosinone		Italy	03100
18	Ospedale S. Antonio Abate	Gallarate		Italy	21013
19	Ospedale San Martino	Genoa		Italy	16132
20	Ospedale L'Aquila	L'Aquila		Italy	67100
21	Ospedale Santa Maria Goretti	Latina		Italy	04100
22	Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE	Lecce		Italy
23	Ospedale Maggiore Lodi	Lodi		Italy	I-20075
24	Azienda Ospedaliera Universitaria - Policlinico G. Martino	Messina		Italy	98125
25	Ospedale Niguarda Ca'Granda	Milan		Italy	20162
26	Azienda Ospedaliera - Universitaria di Modena	Modena		Italy	41100
27	Azienda Ospedaliera di Rilievo Nazionale A.Cardarelli	Naples		Italy	80127
28	Federico II University Medical School	Naples		Italy	80131
29	Ospedale S. Gennaro ASL NA1	Naples		Italy	80131
30	Inferiore U.O. Medicina Interna Ematologia ed Oncologia P.O. Umberto I	Nocera Inferiore		Italy
31	Amedeo Avogadro University of Eastern Piedmont	Novara		Italy	I-28100
32	Ospedale San Francesco	Nuoro		Italy	08100
33	Azienda Ospedale S. Luigi at University of Torino	Orbassano		Italy	10043
34	Azienda Ospedaliera di Padova	Padova		Italy	35128
35	Policlinico - Cattedra di Ematologia	Palermo		Italy	90100
36	Ospedale Cervello	Palermo		Italy	90146
37	Ospedale La Maddalena - Palermo	Palermo		Italy
38	Fondazione I.R.C.C.S. Policlinico San Matteo	Pavia		Italy	27100
39	University of Pavia	Pavia		Italy	27100
40	Perugia Regional Cancer Center	Perugia		Italy	06122
41	Azienda Ospedale - d S. Salvatore	Pesaro		Italy	61100
42	Ospedale Civile Pescara	Pescara		Italy	65100
43	Azienda Ospedaliera Pisana	Pisa		Italy
44	Azienda Ospedaliera San Carlo - Potenza	Potenza		Italy	85100
45	Ospedale Sta. Maria Delle Croci	Ravenna		Italy	48100
46	Ospedale S. M. delle Croci	Ravenna		Italy	I-48100
47	Azienda Ospedaliera Bianchi Melacrino Morelli	Reggio Calabria		Italy	89100
48	Arcispedale S. Maria Nuova	Reggio Emilia		Italy	42100
49	Ospedale Oncologico Regionale	RIONERO in VULTURE		Italy	I-58028
50	Ospedale Sant' Eugenio	Rome		Italy	00144
51	Azienda Ospedaliera S. Camillo-Forlanini	Rome		Italy	00151
52	University Campus Bio-Medico	Rome		Italy	00155
53	Istituto Regina Elena	Rome		Italy	00161
54	Universita Degli Studi "La Sapeinza"	Rome		Italy	00161
55	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome		Italy	00168
56	H. San Giovanni-Addolorata Hospital	Rome		Italy	00184
57	Ospedale di Ronciglione	Ronciglione		Italy	01037
58	IRCCS "Casa Sollievo della Sofferenza"	San Giovanni Rotondo		Italy	71013
59	Istituto di Ematologia Universita - University di Sassari	Sassari		Italy	07100
60	Azienda Ospedale E. Morelli	Sondalo		Italy	23039
61	Ospedale S. Vincenzo	Taormina		Italy	98039
62	Ospedal SS Annunziata	Taranto		Italy	74100
63	Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino	Turin		Italy	10126
64	Ospedale Giovanni Bosco	Turin		Italy
65	Policlinico Universitario Udine	Udine		Italy	33100
66	Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi	Verona		Italy

Sponsors and Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

• Study Chair: Roberto Foa, MD, Universita Degli Studi "La Sapeinza"

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• GIMEMA Foundation Website

Publications

• Chiaretti S, Vitale A, Vignetti M, Piciocchi A, Fazi P, Elia L, Falini B, Ronco F, Ferrara F, De Fabritiis P, Luppi M, La Nasa G, Tedeschi A, Califano C, Fanin R, Dore F, Mandelli F, Meloni G, Foà R. A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia: final results of the GIMEMA LAL 0904 study. Haematologica. 2016 Dec;101(12):1544-1552. Epub 2016 Aug 11.

• Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
• ClinicalTrials.gov Identifier: NCT00458848
• Other Study ID Numbers: LAL0904; LAL0904; 2004-001738-11
• First Posted: Apr 11, 2007
• Last Update Posted: Feb 15, 2019
• Last Verified: Sep 1, 2018

• Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto: B-cell adult acute lymphoblastic leukemia; T-cell adult acute lymphoblastic leukemia; untreated adult acute lymphoblastic leukemia; L1 adult acute lymphoblastic leukemia; L2 adult acute lymphoblastic leukemia; TdT positive adult acute lymphoblastic leukemia
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Prednisone; Methylprednisolone; Methotrexate; Etoposide; Vincristine; Imatinib Mesylate; Daunorubicin; Asparaginase; Mitoxantrone; Mercaptopurine; Idarubicin

Study Results

Participant Flow

Pre-assignment Detail	We are reporting on the subset of patients that was treated according to amendment three, in which Imatinib was given only at induction.

Arm/Group Title	Philadelphia Positive, Imatinib Only in Induction Therapy
Arm/Group Description	These subset of patients was treated according to amendment three, in which Imatinib was given only at induction.
Period Title: Overall Study
STARTED	51
COMPLETED	51
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Philadelphia Positive, Imatinib Only in Induction Therapy
Arm/Group Description	In this protocol, adult Philadelphia positive acute lymphoblastic leukemia patients were treated with chemotherapy for induction and consolidation, followed by maintenance with imatinib. The protocol was subsequently amended and imatinib was incorporated in the induction and post-remission phase together with chemotherapy. Due to the toxicity of this combined approach, the protocol was further amended to a sequential scheme based on imatinib plus steroids as induction, followed by consolidation with chemotherapy plus imatinib and, when applicable, by a hematopoietic stem cell transplant. Thus, we have analyzed only this subset of patients as it was not feasible to analyzed all patients enrolled due also to the disease itself.
Overall Participants	51
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	45.94
Sex: Female, Male (Count of Participants)
Female	28 54.9%
Male	23 45.1%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
Italy	51 100%
White Blood Cells (WBC) at diagnosis-nsr (10^9 cells/L) [Median (Full Range) ]
Median (Full Range) [10^9 cells/L]	28.00
BCR transcript-molecular at diagnosis (participants) [Number]
p190	39 76.5%
p210	7 13.7%
p190/p210	5 9.8%
Pre-treatment response (participants) [Number]
Non responder-blasts reduction <75%	10 19.6%
Responder-blasts reduction >=75%	38 74.5%
Frequency missing	3 5.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Reaching Disease Free Survival
Time Frame	At 60 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Philadelphia Positive, Imatinib Only in Induction Therapy
Arm/Group Description	In this protocol, adult Philadelphia positive acute lymphoblastic leukemia patients were treated with chemotherapy for induction and consolidation, followed by maintenance with imatinib. The protocol was subsequently amended and imatinib was incorporated in the induction and post-remission phase together with chemotherapy. Due to the toxicity of this combined approach, the protocol was further amended to a sequential scheme based on imatinib plus steroids as induction, followed by consolidation with chemotherapy plus imatinib and, when applicable, by a hematopoietic stem cell transplant. Thus, we have analyzed only this subset of patients as it was not feasible to analyzed all patients enrolled due also to the disease itself.
Measure Participants	51
Number [percentage of participants]	45.8 89.8%

2. Secondary Outcome

Title	Number of Patients Reaching Complete Hematological Response After Induction Therapy
Time Frame	At the end of induction, day +50

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Philadelphia Positive, Imatinib Only in Induction Therapy
Arm/Group Description	In this protocol, adult Philadelphia positive acute lymphoblastic leukemia patients were treated with chemotherapy for induction and consolidation, followed by maintenance with imatinib. The protocol was subsequently amended and imatinib was incorporated in the induction and post-remission phase together with chemotherapy. Due to the toxicity of this combined approach, the protocol was further amended to a sequential scheme based on imatinib plus steroids as induction, followed by consolidation with chemotherapy plus imatinib and, when applicable, by a hematopoietic stem cell transplant. Thus, we have analyzed only this subset of patients as it was not feasible to analyzed all patients enrolled due also to the disease itself.
Measure Participants	51
Number [participants]	49 96.1%

3. Secondary Outcome

Title	Percentage of Participants Reaching Overall Survival
Description	Overall survival from diagnosis
Time Frame	At 60 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Philadelphia Positive, Imatinib Only in Induction Therapy
Arm/Group Description	In this protocol, adult Philadelphia positive acute lymphoblastic leukemia patients were treated with chemotherapy for induction and consolidation, followed by maintenance with imatinib. The protocol was subsequently amended and imatinib was incorporated in the induction and post-remission phase together with chemotherapy. Due to the toxicity of this combined approach, the protocol was further amended to a sequential scheme based on imatinib plus steroids as induction, followed by consolidation with chemotherapy plus imatinib and, when applicable, by a hematopoietic stem cell transplant. Thus, we have analyzed only this subset of patients as it was not feasible to analyzed all patients enrolled due also to the disease itself.
Measure Participants	51
Number [percentage of patients]	48.8

Adverse Events

Time Frame	34 months
Adverse Event Reporting Description	Only serious adverse events are reported.
Arm/Group Title	Philadelphia Positive, Imatinib Only in Induction Therapy
Arm/Group Description	In this protocol, adult Philadelphia positive acute lymphoblastic leukemia patients were treated with chemotherapy for induction and consolidation, followed by maintenance with imatinib. The protocol was subsequently amended and imatinib was incorporated in the induction and post-remission phase together with chemotherapy. Due to the toxicity of this combined approach, the protocol was further amended to a sequential scheme based on imatinib plus steroids as induction, followed by consolidation with chemotherapy plus imatinib and, when applicable, by a hematopoietic stem cell transplant. Thus, we have analyzed only this subset of patients as it was not feasible to analyzed all patients enrolled due also to the disease itself.
All Cause Mortality
	Philadelphia Positive, Imatinib Only in Induction Therapy
	Affected / at Risk (%)	# Events
Total	2/51 (3.9%)
Serious Adverse Events
	Philadelphia Positive, Imatinib Only in Induction Therapy
	Affected / at Risk (%)	# Events
Total	7/51 (13.7%)
Gastrointestinal disorders
Abdominal pain	1/51 (2%)	1
General disorders
Death	2/51 (3.9%)	2
Pyrexia	1/51 (2%)	1
Nervous system disorders
Headache	1/51 (2%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/51 (2%)	1
Vascular disorders
Intra-abdominal haematoma	1/51 (2%)	1
Other (Not Including Serious) Adverse Events
	Philadelphia Positive, Imatinib Only in Induction Therapy
	Affected / at Risk (%)	# Events
Total	0/51 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.