Treatment of Mature B-ALL and Burkitt Lymphoma (BL) in Adult Patients. BURKIMAB-14.

Study Overview
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Brief Summary
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Rituximab combined with a specific intensive chemotherapy is considered the standard treatment for newly diagnosed patients with mature B leukemia/lymphoma. However, the toxicity of this therapy is high. The purpose of this trial is to reduce the dose intensity of the chemotherapy blocks once the patient has achieved complete response. With this approach the investigators expect to maintain the efficacy and to reduce the toxicity of the chemotherapy, specially the rate of deaths in complete response.

Detailed Description
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Patients younger than 55 years in complete response after two blocks of rituximab and specific intensive chemotherapy will receive four additional blocks of rituximab and attenuated chemotherapy (reduction by 33% of the dose of cyclophosphamide, methotrexate and cytarabine) followed by additional rituximab doses as consolidation. Patients older than 55 years will receive the six blocks with attenuated chemotherapy.

Official Title
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Treatment of Mature B-ALL and Burkitt Lymphoma (BL) in Adult Patients. BURKIMAB-14.

Conditions
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Mature B-Cell Leukemia Burkitt Type, Burkitt Lymphoma (BL), Unclassifiable Lymphoma Between DCBL and BL

Intervention / Treatment
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* Drug: Rituximab
* Drug: Methotrexate
* Drug: Dexamethasone
* Drug: Iphosphamid
* Drug: Vincristine
* Drug: Etoposide
* Drug: Cytarabine
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vindesine
* Drug: Cytarabine
* Drug: Methotrexate
* Drug: Hydrocortisone
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old Patients diagnosed with de novo mature B-ALL, Burkitt lymphoma (BL). Under physician's criteria, patients with unclassified B-lymphoma with intermediate characteristics between DLBCL and BL could be included. Candidate to intensive treatment. Exclusion Criteria: Other ALL subtype different from mature B-ALL/BL Severe complications not due to mature B-ALL/BL (eg, sepsis, pneumonia, shock or hemorrhage) at diagnosis. Renal failure not due to mature B-ALL /BL Heart or liver failure Severe lung disease Secondary mature B-ALL/BL Hypersensitivity to foreign proteins Previous treatment with cytotoxic drugs Pregnancy/breastfeeding Severe psychiatric disease Lack of social or familiar support

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy<br>Pts with biological age up to 55 y with advanced stage will receive 6 cycles of intensive treatment: blocks (A1-B1-C1-A2-B2-C2). If after A1 and B1 cycles CR is observed, the rest of the cycles will be administered with reduced doses. In pts with biological age >55 y with advanced stage block will receive A and B with attenuated doses (A1*-B1*-A2*-B2*-A3*-B3*). Pts with biological age up to 55 y with localized stage (non-bulky I or II) with CR after 2 cycles will finish treatment after 4 blocks. If CR is not reached, patients will complete the 6 treatment cycles. Pts with a biological age >55 y with localized stage (non-bulky I or II) with CR after 2 cycles will finish treatment after 4 attenuated blocks (A1*-B1*-A2*-B2*). If CR is not reached, patients will complete the 6 cycles of treatment. | Drug: Rituximab<br>* Rituximab 375 mg/m² IV. Day 1. Cycles: A1/A1*, B1/B1*, C1/A2*, A2/B2*, B2/A3*, C2/B3*. Two additional doses after 6 cycles in case of localized stage patients without CR after four cycles or advanced stage patients.<br>Drug: Methotrexate<br>* Methotrexate 1500 mg/m² IV 24h-infusion. Day 2. Cycles: A1, B1, C1 (1000 mg/m² if patient in CR) , A2 (1000 mg/m² if patient in CR), B2 (1000 mg/m² if patient in CR) , C2 (1000 mg/m² if patient in CR) Methotrexate 500 mg/m² IV 24h-infusion. Day 2. Cycles: A1*, B1*, A2*, B2*, A3*, B3*<br>Drug: Dexamethasone<br>* Dexamethasone 10 mg/m² PO or IV bolus. Days: 2 to 6. Cycles: A1/A1*, B1/B1*, C1/A2*, A2/B2*, B2/A3*, C2/B3*.<br>Drug: Iphosphamid<br>* Iphosphamid 800 mg/m² IV in 1 hour. Days: 2 to 6. Cycles: A1, A2 (500 mg/m² if patient in CR). Iphosphamid 400 mg/m² IV in 1 hour. Days: 2 to 6. Cycles: A1*.<br>Drug: Vincristine<br>* Vincristine 2 mg IV bolus. Day 2. Cycles: A1, B1, A2, B2 Vincristine 1 mg IV bolus. Day 2. Cycles: B1*, B2*, B3*<br>Drug: Etoposide<br>* Etoposide (VP16) 100 mg/m² IV in 1 hour. Days: 5, 6. Cycle: A1, A2. Etoposide (VP16) 250 mg/m² IV in 1 hour. Days: 5, 6. Cycle: C1, C2. Etoposide (VP16) 60 mg/m² IV in 1 hour. Days: 5, 6. Cycle: A1*, A2*, A3*.<br>Drug: Cytarabine<br>* Cytarabine 150 mg/m² IV in 1 hour every 12 hours. Days: 5, 6. Cycles: A1, A2 Cytarabine 2 g/m² IV in 3 hours every 12 hours. Day: 6. Cycle: C1 (1.5 g/m² if patient in CR), C2 (1.5 g/m² if patient in CR) Cytarabine 60 mg/m² IV in 1 hour every 12 hours. Days: 5, 6. Cycles: A1*, A2*, A3*<br>Drug: Cyclophosphamide<br>* Cyclophosphamide 200 mg/m² IV in 1 hour. Days 1 to 5. Pre-phase. Cyclophosphamide 200 mg/m² IV in 1 hour. Days 2 to 6. Cycles: B1, B2, B1*, B2*, B3*<br>Drug: Doxorubicin<br>* Doxorubicin 25 mg/m² IV in 15 min. Days 5 and 6. Cycles: B1/B1*, B2, B2*, B3*<br>Drug: Vindesine<br>* Vindesine 3 mg/m2 (max 5 mg) IV bolus. Day 2. Cycles: C1, C2<br>Drug: Cytarabine<br>* Cytarabine 30 mg IT. Days 2 and 6. Cycles A1, B1, A2, B2<br>Drug: Methotrexate<br>* Methotrexate 12 mg IT. Day 1. Pre-phase Methotrexate 12 mg IT. Days 2 and 6. Cycles: A1, B1, A2, B2 Methotrexate 15 mg IT. Day 2. Cycles: A1*, B1*, A2*, B2*, A3*, B3*<br>Drug: Hydrocortisone<br>* Hydrocortisone 20 mg IT. Days 2 and 6. Cycles: A1, B1, A2, B2<br>Drug: Prednisone<br>* Prednisone 60 mg/m2 PO or IV bolus. Days 1 to 5. Pre-phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Defined as the time from diagnosis to death by any cause or last follow-up. | Throughout the study period. Approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Defined as the time from diagnosis to progression disease, relapse or death by any cause or last follow-up. | Throughout the study period. Approximately 3 years | 
| Number of patients with toxicity during the treatment period. | Number of patients experiencing different toxicities during the treatment period, classified according to severity and graded according to NCTCAE V4.0 | Throughout the study period. Approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Burkitt lymphoma, Mature B-ALL, Adult