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Enzyme

Combination Chemotherapy for T-Cell Leukemia/Lymphoma

Phase 3
Waitlist Available
Led By Stuart S Winter
Research Sponsored by National Cancer Institute (NCI)
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
For the management of airway compromise, patients who have received emergent chest irradiation up to 600 cGy will be eligible for this study
A diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (cluster of differentiation [CD]19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a; if surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including transmission disequilibrium test (TdT), CD34 or CD99 will be assessed for expression; cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory
Must not have
For T-NHL patients the following additional exclusion criteria apply: B-precursor lymphoblastic lymphoma, Morphologically unclassifiable lymphoma, Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma, CNS3-positive or testicular involvement
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 4 years from end of induction
Awards & highlights
No Placebo-Only Group
Pivotal Trial

Summary

This trial is studying different combination chemotherapy regimens for T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma.

Who is the study for?
This trial is for young patients with newly diagnosed T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. It's not open to those with Down syndrome, unclassifiable lymphoma, CNS3-positive/testicular involvement, pregnant/lactating females, or B-precursor lymphoblastic lymphoma.
What is being tested?
The study tests different combination chemotherapy regimens to see which is more effective against T-cell leukemia/lymphoma. Patients receive a common induction therapy first and then get assigned varying treatments based on their risk level and response.
What are the potential side effects?
Chemotherapy drugs may cause side effects like nausea, hair loss, fatigue, increased infection risk due to low blood cell counts, mouth sores, and potential damage to organs such as the heart or liver.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
Select...
I've had emergency chest radiation up to 600 cGy for airway issues.
Select...
My leukemia is classified as T-ALL based on specific cell markers.
Select...
I have been newly diagnosed with T-ALL or T-NHL at stage II-IV.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
Select...
My T-NHL does not include specific types like B-precursor lymphoblastic lymphoma or involve the brain/testicles.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~4 years from end of induction
This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 years from end of induction for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV)
Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV)
Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV)
+2 more
Secondary study objectives
Cumulative Incidence of CNS Relapse for T-ALL by Risk Group

Side effects data

From 2021 Phase 3 trial • 3154 Patients • NCT00075725
79%
Neutrophil count decreased
66%
Febrile neutropenia
64%
Infections and infestations - Other, specify
47%
Alanine aminotransferase increased
38%
White blood cell decreased
35%
Platelet count decreased
32%
Anemia
25%
Aspartate aminotransferase increased
23%
Hypokalemia
15%
Mucositis oral
11%
Catheter related infection
11%
Anaphylaxis
9%
Dehydration
9%
Hyperglycemia
9%
Lung infection
9%
Fever
9%
Hyponatremia
8%
Diarrhea
8%
Upper respiratory infection
8%
Vomiting
8%
Lymphocyte count decreased
7%
Anorexia
6%
Otitis media
6%
Enterocolitis infectious
5%
Fibrinogen decreased
5%
Hypertension
4%
Hypoglycemia
4%
Abdominal pain
4%
Peripheral sensory neuropathy
4%
Skin infection
4%
Oral pain
4%
GGT increased
4%
Hypoxia
4%
Weight loss
3%
Sinusitis
3%
Constipation
3%
Urinary tract infection
3%
Activated partial thromboplastin time prolonged
3%
Blood bilirubin increased
3%
Peripheral motor neuropathy
3%
Hypoalbuminemia
3%
Lipase increased
3%
Hypophosphatemia
3%
Hyperkalemia
2%
Pain in extremity
2%
Headache
2%
Nausea
2%
Bronchial infection
2%
Blood and lymphatic system disorders - Other, specify
2%
Seizure
2%
Pneumonitis
2%
Serum amylase increased
2%
Hypocalcemia
2%
Pancreatitis
1%
Back pain
1%
Wound infection
1%
Nervous system disorders - Other, specify
1%
Pleural effusion
1%
Fatigue
1%
Agitation
1%
Syncope
1%
Gait disturbance
1%
Epistaxis
1%
Ileus
1%
Personality change
1%
Pain
1%
Bronchospasm
1%
Abdominal distension
1%
Abdominal infection
1%
Alkaline phosphatase increased
1%
Anorectal infection
1%
Bone infection
1%
Dysphasia
1%
Flu like symptoms
1%
Gastritis
1%
Hypotension
1%
INR increased
1%
Insomnia
1%
Muscle weakness lower limb
1%
Myalgia
1%
Otitis externa
1%
Sepsis
1%
Typhlitis
1%
Vascular disorders - Other, specify
1%
Cough
1%
Gum infection
1%
Hypermagnesemia
1%
Investigations - Other, specify
1%
Mucosal infection
1%
Portal hypertension
1%
Thromboembolic event
1%
Rectal mucositis
1%
Respiratory, thoracic and mediastinal disorders - Other, specify
100%
80%
60%
40%
20%
0%
Study treatment Arm
Prednisone and High Dose Methotrexate < 10 Yrs Old
Prednisone and High Dose Methotrexate (Non Randomly Assigned)
Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old
Dexamethasone, High Dose Methotrexate (IM) < 10 Years
Prednisone, Capezzi Methotrexate >= 10 Years
Prednisone, Capizzi Methotrexate <10 Years
Dexamethasone and Capizzi Methotrexate Patients < 10 Years
Dexamethasone, High Dose Methotrexate (Non Randomly Assigned)
Prednisone and High Dose Methotrexate >=10 Years
Dexamethasone, High Dose Methotrexate (IM) >= 10 Years
Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random)
Prednisone, Capezzi Methotrexate (Down's Syndrome)

Awards & Highlights

No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.
Pivotal Trial
The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

17Treatment groups
Experimental Treatment
Active Control
Group I: Group 0 Induction TherapyExperimental Treatment6 Interventions
All patients (T-ALL and T-LLy) receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; prednisone IV or PO twice daily BID on days 1-28; pegaspargase IM (may give IV over 1 to 2 hours) on day 4, 5, or 6; daunorubicin hydrochloride IV on days 1, 8, 15 and 22; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease).
Group II: Group I Arm III (Maintenance chemotherapy)Active Control3 Interventions
Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL) and all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL).
Group III: Group I Arm I (Interim maintenance chemotherapy)Active Control4 Interventions
Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase\* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS also receive leucovorin calcium PO 48 and 60 hours after each methotrexate IT dose (DS patients excluded as of 09/29/10). Note: \*Patients with an allergy to pegaspargase receive Erwinia asparaginase on days 2, 4, 6, 8, 10, 12, 22, 24, 26, 28, 30, and 32.
Group IV: Group I Arm II (Delayed intensification chemotherapy)Active Control8 Interventions
Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49.
Group V: Group I Arm III (Delayed intensification chemotherapy)Active Control9 Interventions
Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10).
Group VI: Group I Arm III (Consolidation chemotherapy)Active Control8 Interventions
Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT.
Group VII: Group I Arm II (Consolidation chemotherapy)Active Control8 Interventions
Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33 (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35. Patients with high risk T-LLy were either randomized to Arm I or Arm II. Patients with T-LLy who failed induction therapy were assigned to Arm II.
Group VIII: Group I Arm I (Consolidation chemotherapy)Active Control8 Interventions
Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT. Patients with standard risk T-LLy received Arm I, and those with high risk T-LLy were randomized between Arm I and Arm II combination chemotherapy.
Group IX: Group I Arm I (Delayed intensification chemotherapyActive Control9 Interventions
Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10). Standard risk T-LLy patients were assigned to Arm I and those with high risk were randomized between Arm I and Arm II.
Group X: Group I Arm II (Maintenance chemotherapy)Active Control5 Interventions
Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL).
Group XI: Group I Arm III (Interim maintenance chemotherapy)Active Control5 Interventions
Patients receive HDMTX IV over 24 hours and vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses.
Group XII: Group I Arm IV (Delayed intensification chemotherapy)Active Control9 Interventions
Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age); doxorubicin IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49.
Group XIII: Group I Arm IV (Interim maintenance chemotherapy)Active Control5 Interventions
Patients receive HDMTX IV over 24 hours and vincristine IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses.
Group XIV: Group I Arm IV (Maintenance chemotherapy)Active Control5 Interventions
Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine, prednisone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL).
Group XV: Group I Arm I (Maintenance chemotherapy)Active Control5 Interventions
Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL), all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL).
Group XVI: Group 1 Arm IV (Consolidation chemotherapy)Active Control7 Interventions
Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33 (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35.
Group XVII: Group I Arm II (Interim maintenance chemotherapy)Active Control4 Interventions
Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase\* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Note: \*Patients with an allergy to pegaspargase receive Erwinia asparaginase on Monday, Wednesday and Friday for two consecutive weeks starting the day of asparaginase substitution.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Cytarabine
2016
Completed Phase 3
~3330
Vincristine Sulfate
2005
Completed Phase 3
~10270
Prednisone
2014
Completed Phase 4
~2500
Daunorubicin Hydrochloride
2011
Completed Phase 3
~5330
Methotrexate
2019
Completed Phase 4
~4400
Pegaspargase
2005
Completed Phase 3
~9260

Find a Location

Who is running the clinical trial?

National Cancer Institute (NCI)Lead Sponsor
13,920 Previous Clinical Trials
41,015,039 Total Patients Enrolled
Stuart S WinterPrincipal InvestigatorChildren's Oncology Group

Media Library

Asparaginase (Enzyme) Clinical Trial Eligibility Overview. Trial Name: NCT00408005 — Phase 3
Acute Lymphoblastic Leukemia Research Study Groups: Group I Arm III (Maintenance chemotherapy), Group I Arm I (Interim maintenance chemotherapy), Group I Arm II (Delayed intensification chemotherapy), Group I Arm III (Delayed intensification chemotherapy), Group I Arm III (Consolidation chemotherapy), Group I Arm II (Consolidation chemotherapy), Group I Arm I (Consolidation chemotherapy), Group I Arm I (Delayed intensification chemotherapy, Group I Arm II (Maintenance chemotherapy), Group I Arm III (Interim maintenance chemotherapy), Group I Arm IV (Delayed intensification chemotherapy), Group I Arm IV (Interim maintenance chemotherapy), Group I Arm IV (Maintenance chemotherapy), Group I Arm I (Maintenance chemotherapy), Group 0 Induction Therapy, Group 1 Arm IV (Consolidation chemotherapy), Group I Arm II (Interim maintenance chemotherapy)
Acute Lymphoblastic Leukemia Clinical Trial 2023: Asparaginase Highlights & Side Effects. Trial Name: NCT00408005 — Phase 3
Asparaginase (Enzyme) 2023 Treatment Timeline for Medical Study. Trial Name: NCT00408005 — Phase 3
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