Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Childhood Acute Lymphoblastic Leukemia

Anti-Inflammatory Agents

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Micronutrients

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Hematinics

Vitamins

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Cytarabine

Doxorubicin

Liposomal doxorubicin

Dexamethasone

Leucovorin

Methotrexate

Vincristine

Dexamethasone acetate

Pegaspargase

Asparaginase

Ixazomib

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Antiviral Agents

Antidotes

Protective Agents

Trace Elements

Tubulin Modulators

Antimitotic Agents

HIV Protease Inhibitors

Protease Inhibitors

Folinic Acid

Folate

Vitamin B9

Patients will be treated on ixazomib at 1.6 mg/m\^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m\^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m\^2 on Days 2 and 15, Doxorubicin at 60 mg/m\^2 on Days 1, Dexamethasone IV/PO at 10 mg/m\^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. This arm is the starting Dose Level for patients being enrolled.

Patients will be treated on ixazomib at 2.0 mg/m\^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m\^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m\^2 on Days 2 and 15, Doxorubicin at 60 mg/m\^2 on Days 1, Dexamethasone IV/PO at 10 mg/m\^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. Patients will be treated at this arm Dose Level once patient accrual at Dose Level 1 has been completed and dose escalation is allowed as defined by the 3+3 design.

Patients will be treated on ixazomib at 1.2 mg/m\^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m\^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m\^2 on Days 2 and 15, Doxorubicin at 60 mg/m\^2 on Days 1, Dexamethasone IV/PO at 10 mg/m\^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. This arm Dose Level -1 is needed only if de-escalation from Dose Level 1 is required.

Patients will be treated on ixazomib at 1.6 mg/m\^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m\^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m\^2 on Days 2 and 15, Doxorubicin at 60 mg/m\^2 on Days 1, Dexamethasone IV/PO at 10 mg/m\^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. Leucovorin PO/IV at 5 mg/m\^2/dose X 2 doses given 24 and 30 hours after IT Methotrexate or Triple IT will also be given on this arm. This arm is only for patients with Down syndrome (Stratum B).

Days 1, 4, 8, and 11. Note: at least 72 hours must have elapsed between doses

Dose Phase 1 - Assigned upon study entry.

Phase 2 - PO formulation at RP2D

IV push over 1 minute or infusion via minibag as per institutional policy

Days 1, 8, 15 and 22

Dose: ≥ 1 year: 1.5mg/m2/dose (maximum dose 2mg)

≥ 6 months and \< 1 year: 1.2mg/m2/dose

\< 6 months: 1mg/m2/dose

Days 1-14

Dose: ≥ 1 year: 10mg/m2/day, divided BID (i.e., 5mg/m2/dose, BID)

≥ 6 months and \< 1 year: 8mg/m2/day, divided BID (i.e., 4 mg/m2/dose, BID)

\< 6 months: 7mg/m2/day, divided BID (i.e., 3.5 mg/m2/dose, BID)

Days 2, 15

Dose ≥ 1 year: 2,500 International units (IU)/m2/dose

≥ 6 months and \< 1 year: 2,000 IU/m2/dose

\< 6 months: 1,750 IU/m2/dose

Patient with allergic reaction to Pegaspargase can be given Erwinase IM/IV on Mon/Wed/Fri (or every other day per institutional standard) x 6 doses for each dose of Pegaspargase.

Dosing guideline for Erwinase:

* 1 year: 25,000 IU/m2/dose
* 6 months and \< 1 year: 20,000 IU/m2/dose

\< 6 months: 17,500 IU/m2/dose

Day 1

Dose ≥ 1 year: 60mg/m2/dose

≥ 6 months and \< 1 year: 48 mg/m2/dose

\< 6 months: 42mg/m2/dose

For patients with CNS 1 or CNS 2, on Days 1, 15, and 29

Methotrexate (IT)

For patients with CNS 3, on Days 1, 8, 15, 22, and 29

Triple IT (Methotrexate, Hydrocortisone, Cytarabine)

For patients with Down syndrome only, on Days 2, 9, 16, 23, and 30 (based on dates when IT Methotrexate or Triple IT is given)

Terzah Horton, MD

This is a phase 1/2 study of a drug called Ixazomib in combination with cytotoxic chemotherapy consisting of Vincristine, Dexamethasone, Asparaginase, and Doxorubicin (VXLD).

The phase 1 study is to determine the maximum tolerated dose (MTD) of the PO formulation, followed by a screening phase 2 study to investigate the efficacy of ixazomib in combination with chemotherapy in children with relapsed ALL and lymphoblastic lymphoma (LLy). The single arm, screening phase 2 design will allow us to use a minimal number of patients to obtain preliminary information about treatment efficacy. Discovering a safe and tolerable dose of ixazomib in a PO formulation and the preliminary efficacy data will significantly increase the possibility of ixazomib moving forward in frontline pediatric treatment protocols in both intense chemotherapy courses and maintenance courses.

PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

A TACL Phase 1/2 Study of PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma IND# 140730

The incidence of dose limiting toxicity (DLT) will be measured only during block 1

Takeda

Children's Hospital Los Angeles

Therapeutic Advances in Childhood Leukemia Consortium

Neuroprotective Agents

Cyclophosphamide

Prednisone

Daunorubicin

Prednisolone

Ifosfamide

Mercaptopurine

Thioguanine

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Vindesine

Isophosphamide mustard

Antineoplastic Agents, Alkylating

Alkylating Agents

1. cytoreductive prephase with prednisone
2. standard induction phase (protocol Ia-prednisone)
3. consolidation phase (protocol Ib)
4. non-HR extra-compartment phase (protocol M)
5. maintenance therapy

1. cytoreductive prephase with prednisone
2. experimental induction phase (protocol Ia-dexamethasone)
3. consolidation phase (protocol Ib)
4. non-HR extra-compartment Phase (protocol M)
5. maintenance therapy

1. cytoreductive prephase with prednisone
2. standard induction phase (protocol Ia-prednisone)
3. consolidation phase (protocol Ib)
4. non-HR extra-compartment phase (protocol M)
5. reintensification phase (protocol II)
6. maintenance therapy

1. cytoreductive prephase with prednisone
2. experimental induction phase (protocol Ia-dexamethasone)
3. consolidation phase (protocol Ib)
4. non-HR extra-compartment phase (protocol M)
5. reintensification phase (protocol II)
6. maintenance therapy

1. cytoreductive prephase with prednisone
2. standard induction phase (protocol Ia-prednisone)
3. consolidation phase (protocol Ib\*)
4. HR extra-compartment phase (intensified protocol M)
5. reintensification phase (protocol II)
6. maintenance therapy

1. cytoreductive prephase with prednisone
2. experimental induction phase (protocol Ia-dexamethasone)
3. consolidation phase (protocol Ib\*)
4. HR extra-compartment phase (intensified protocol M)
5. reintensification phase (protocol II)
6. maintenance therapy

Part of standard chemotherapy and included in the experimental treatment phase protocol Ib\* (Randomization 2) and in the experimental treatment phase Intensified Protocol M (Randomization R2)

No involvement of CNS: Part of standard chemotherapy and included in the experimental treatment phase protocol Ib\* (Randomization 2) and in the experimental treatment phase Intensified Protocol M (Randomization R2).

Involvement of CNS: Part of standard chemotherapy and included in the experimental treatment phase Protocol Ia-Dexamethasone (Randomization R1), in the experimental treatment phase Protocol Ib\* (Randomization R2) and in the experimental treatment phase Intensified Protocol M (Randomization R2)

Part of the experimental therapy in Randomization R1 (Protocol Ia-Dexamethasone) and in Randomization R2 (Intensified Protocol M)

Part of standard chemotherapy and included in the experimental treatment phase Protocol Ia-Dexamethasone (Randomization R1), in the experimental treatment phase Protocol Ib\* (Randomization R2) and in the experimental treatment phase Intensified Protocol M (Randomization R2)

Part of the experimental therapy in Randomization R2 (Intensified Protocol M)

6-Mercaptopurine

Part of standard chemotherapy and included in the experimental treatment phase Protocol Ia-Dexamethasone (Randomization R1) and in the experimental treatment phase Protocol Ib\* (Randomization R2)

PEG asparaginase

No involvement of CNS: Part of standard chemotherapy. Involvement of CNS: Part of standard chemotherapy and included in the experimental treatment phase Protocol Ia-Dexamethasone (Randomization R1), in the experimental treatment phase Protocol Ib\* (Randomization R2) and in the experimental treatment phase Intensified Protocol M (Randomization R2

Part of standard chemotherapy and included in the experimental treatment phase Protocol Ia-Dexamethasone (Randomization R1) and in the experimental treatment phase Intensified Protocol M (Randomization R2)

Birgit Burkhardt, Prof. Dr. Dr.

Primary objectives:

* Randomization R1, all patients eligible: To examine, whether the cumulative incidence of relapses with involvement of the CNS (CNS relapse, pCICR) can be decreased by a modified induction therapy including dexamethasone (experimental arm) instead of prednisone (standard arm)
* Randomization R2, only patients with high risk LBL eligible: to examine, whether the probability of event-free survival (pEFS) in these patients can be improved by receiving an intensified treatment arm versus a standard treatment arm (as used in the EURO-LB 02)

The trial LBL 2018 is a collaborative prospective, multi-national, multi-center, randomized clinical trial for the treatment of children and adolescents with newly diagnosed lymphoblastic lymphoma.

The LBL 2018 trial will be open for the qualified centers of following participating study Groups (core study cohort): AIEOP (Italy), BFM (Austria, Czech Republic, Germany, Switzerland), BSPHO (Belgium), CoALL (Germany), DCOG (The Netherlands), NOPHO (Denmark, Finland, Norway, Sweden), PPLLSG (Poland), SEHOP (Spain) and SFCE (France). HKPHOSG (Hong Kong), HPOG (Hungary), ISPHO (Israel), NSPHO (Moscow), SHOP (Portugal) and SPS (Slovak Republic) start patient recruitment into the extended study cohort (without randomization). Over the trial period study groups may switch from the extended study cohort to the core study cohort.

Primary objectives:

* Randomization R1, all patients eligible: To examine, whether the cumulative incidence of relapses with involvement of the CNS (CNS relapse, pCICR) can be decreased by a modified induction therapy including dexamethasone (experimental arm) instead of prednisone (standard arm)
* Randomization R2, only patients with high risk LBL eligible: to examine, whether the probability of event-free survival (pEFS) in these patients can be improved by receiving an intensified treatment arm versus a standard treatment arm (as used in the EURO-LB 02)

Patients are stratified into 3 different risk groups according to CNS status, immunophenotype, genetic markers and stage of disease at diagnosis: high risk group (HR), standard risk group I/II (SR I/II) and standard risk group (SR).

Patients in the risk groups SR I/II and SR are randomized (R1) in two arms after a cytoreductive prephase with prednisone. Patients in standard arm receive the standard induction phase with prednisone. Patients in the experimental arm receive an induction phase with dexamethasone instead of prednisone.

In SR group, induction phase is followed by the consolidation phase, the non-HR extra-compartment phase with HD-MTX (high-dose methotrexate), the reintensification phase and the maintenance therapy for the total therapy duration of 24 months. In SR I/II group, patients receive no reintensification phase. The Induction phase is followed by the consolidation phase, the non-HR extra-compartment phase and the maintenance therapy for the total therapy duration of 24 months.

Patients in the HR group are eligible for randomization (R1) as outlined above. In addition high risk patients are eligible for second randomization (R2) at the end of induction phase. In the standard arm, HR-patients receive the consolidation phase and the non-HR extra-compartment phase. In the experimental arm, HR-patients receive a consolidation phase including two additional doses of PEG asparaginase and the HR-intensified extra-compartment phase consisting of two high risk courses alternating with two HD-MTX courses. Either phase is followed by the reintensification phase and the maintenance therapy for the total therapy duration of 24 months.

Patients with involvement of the CNS (CNS positive) are stratified to the high risk group (HR) and are eligible for both randomizations (R1 and R2). Additionally, patients with CNS involvement (CNS positive) receive intensified intrathecal therapy. Intrathecal therapy consists of TIT (triple intrathecal therapy) after diagnosis of CNS involvement. TIT is administered twice weekly until clearance of blasts in the cerebrospinal fluid is achieved. Further intrathecal therapy is provided at the same points of time as for patients without CNS involvement, but TIT instead of MTX IT. In addition, patients receive four additional doses of TIT during maintenance. Cranial irradiation is omitted for patients with CNS involvement.

International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma

LBL 2018 - International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma

The time to relapse is defined as the time from randomization to the first relapse or the date of last follow-up. Other events (non-response, progressive disease, relapse, second malignancy or death before and in CR) will be taken into account as competing events.

The pEFS is defined as the time from randomization to the first event (non-response, progressive disease, relapse, second malignancy or death from any cause) or date of last follow-up.

Survival (pOS) is defined as time from diagnosis to death due to any cause or to the date of last contact for patients alive

Deutsche Krebshilfe e.V., Bonn (Germany)

University Hospital Muenster

Zhen zijun

Sun xiaofei

With the development of molecular biology and precise medical treatment, new challenges have been raised in the diagnosis and treatment of non-Hodgkin lymphoma (NHL) in children. In recent years, the criteria for clinical staging and efficacy evaluation of NHL in children have been updated. Recent clinical studies of COG in the United States and LMB in France have confirmed that molecular biological markers such as Notch1, PTEN and LOH6q are significantly associated with the prognosis of T-lymphoblastic lymphoma (T-LBL). These molecular biological markers should be included in the new risk stratification system. High-intensity treatment of high-risk patients will improve survival. Recent studies have also suggested that PET/CT is helpful in evaluating residual lesions in patients with lymphoma after chemotherapy. In order to keep pace with the times in the diagnosis, clinical staging, risk stratification, efficacy evaluation and treatment of NHL in children. SCCCG-LBL-2017 was formulated by South China Children's Cancer Group of Non-Hodgkin lymphoma, which mainly updated in clinical staging, efficacy evaluation, risk stratification, treatment,etc..

Research purpose:

1. To investigate the efficacy and safety of SCCCG-LBL-2017 in Chinese children with LBL.
2. To explore the feasibility of risk stratification of T-LBL by combining genotyping.
3. To investigate the correlation between MDD and MRD in lymphoblastic lymphoma and prognosis.
4. To investigate the role of PET/CT in the assessment of residual lymphoblastic lymphoma.
5. To explore the effect of reducing HD-MTX dosage and shortening maintenance therapy time on the efficacy and survival of low-risk LBL patients.
6. To explore the effect of prolonging the duration of maintenance therapy on the efficacy and survival of high-risk LBL patients.

A Prospective Multicenters Clinical Cohort Study of Stratified Treatment of Chinese Children With LBL

A Prospective Multicenter Cohort Study on the Efficacy and Safety of Stratified Treatment of Chinese Children With Lymphoblastic Lymphoma Based on Risk Factors

EFS is defined as time from start of treatment/randomization up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.

OS is defined as time from start of treatment/randomization up to death of any

RFS is defined as time from start of treatment/randomization up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease, or relapse.

Complete response, partial remission, objective effect, stable disease or progressive disease

Rate of patients with acute toxicity defined as grade III/IV/V AE

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma	NCT03817320	ALL, Childhood Lymphoblastic L... Lymphoblastic L...	Ixazomib Vincristine Dexamethasone Asparaginase Doxorubicin Methotrexate (I... Triple IT (Meth... Leucovorin	1 Year - 21 Years	Therapeutic Advances in Childhood Leukemia Consortium
International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma	NCT04043494	Lymphoblastic L...	Cyclophosphamid... Cytarabine Dexamethasone Daunorubicin Doxorubicin Ifosfamide 6-Mercaptopurin... Methotrexate PEG asparaginas... Prednisone Prednisolone Thioguanine Vincristine Vindesine	- 18 Years	University Hospital Muenster
A Prospective Multicenters Clinical Cohort Study of Stratified Treatment of Chinese Children With LBL	NCT03971318	Lymphoma, Non-H... Lymphoblastic L... PTEN Loss NOTCH1 Gene Mut... Pediatric Cance...		1 Year - 18 Years	Sun Yat-sen University
International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma	NCT04043494	Lymphoblastic L...	Cyclophosphamid... Cytarabine Dexamethasone Daunorubicin Doxorubicin Ifosfamide 6-Mercaptopurin... Methotrexate PEG asparaginas... Prednisone Prednisolone Thioguanine Vincristine Vindesine	- 18 Years	University Hospital Muenster
PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma	NCT03817320	ALL, Childhood Lymphoblastic L... Lymphoblastic L...	Ixazomib Vincristine Dexamethasone Asparaginase Doxorubicin Methotrexate (I... Triple IT (Meth... Leucovorin	1 Year - 21 Years	Therapeutic Advances in Childhood Leukemia Consortium

Spots Global Cancer Trial Database for lymphoblastic lymphoma, childhood