Combination Chemotherapy for T-Cell Leukemia/Lymphoma

No longer recruiting at 234 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticonvulsants

Disqualifiers: Pregnancy, Down syndrome, CNS3-positive, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which combination of chemotherapy drugs best treats T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LLy) in young patients. Chemotherapy uses drugs to stop cancer cells from growing or dividing. The trial evaluates different drug combinations to identify the most effective one with the fewest side effects. Participants should have newly diagnosed T-ALL or T-LLy and should not have received prior chemotherapy, except for steroids or certain specific treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, patients with a prior seizure disorder requiring anti-convulsant therapy are not eligible to receive nelarabine, which suggests that some medications may affect eligibility or treatment options.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the drugs used in the trial have varying safety levels, depending on the specific drug and its administration. For example, studies have found that pegaspargase, a type of asparaginase, is usually well-tolerated but can cause allergic reactions in some individuals. Monitoring for blood clotting issues during treatment is important.

Cyclophosphamide, another drug in the trial, is approved for treating various cancers, including blood cancers, but can cause side effects like nausea and hair loss. It also carries risks of infertility and secondary cancers.

Daunorubicin and doxorubicin are chemotherapy drugs that can be effective but may cause heart problems and lower blood cell counts. Dexamethasone, a steroid used in cancer treatment, can help reduce inflammation but might affect mood and cause weight gain.

Methotrexate is approved for treating leukemia but can lead to liver and kidney problems. Nelarabine, used specifically for T-cell leukemia, can cause nerve damage in some patients.

Vincristine is also part of the treatment plan and is approved for treating leukemia. It can cause nerve damage and constipation but is generally considered effective.

Overall, these drugs have long been used in cancer treatment and have well-known safety profiles. Monitoring and managing side effects is crucial for using these medications safely. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination chemotherapy for T-cell leukemia and lymphoma because it uses a multi-drug approach, potentially improving outcomes for patients. Unlike traditional treatments that may focus on fewer drugs, this regimen includes a mix of medications like vincristine sulfate, pegaspargase, and nelarabine, each attacking cancer cells in different ways. This diverse mechanism of action may enhance effectiveness and address the disease from multiple angles. Additionally, the inclusion of high-dose methotrexate, along with tailored dosing schedules, could lead to better disease control and reduced relapse rates. Overall, this treatment aims to provide a more comprehensive attack on cancer cells, offering hope for better patient outcomes.

What evidence suggests that this trial's treatments could be effective for T-cell leukemia/lymphoma?

This trial will evaluate the effectiveness of various chemotherapy combinations for T-cell leukemia and lymphoma. Asparaginase, one of the drugs tested, has been linked to an 87.5% chance of children with acute lymphoblastic leukemia remaining disease-free for 10 years. Cyclophosphamide, another drug in this trial, shows a high success rate, with 77% of T-cell lymphoma patients responding to treatment and 53% achieving complete remission. Methotrexate, especially in high doses, significantly improves survival, with 71.1% of certain T-cell non-Hodgkin lymphoma patients remaining event-free for 5 years. Nelarabine, also part of this trial, has shown a 91% chance of young patients with T-cell acute lymphoblastic leukemia staying disease-free for 4 years. Vincristine, when used with other drugs, leads to a 77% complete remission rate in certain lymphomas. These findings suggest that the combinations tested in this trial could effectively treat T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Stuart S Winter

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I have not had chemotherapy, except for steroids or IT cytarabine.

My leukemia is classified as T-ALL based on specific cell markers.

I have been newly diagnosed with T-ALL or T-NHL at stage II-IV.

Exclusion Criteria

My T-NHL does not include specific types like B-precursor lymphoblastic lymphoma or involve the brain/testicles.

Patients with Down syndrome are ineligible to enroll onto this study

Pregnant or lactating females are ineligible

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

All patients receive a combination of chemotherapy drugs including cytarabine, vincristine sulfate, prednisone, pegaspargase, daunorubicin hydrochloride, and methotrexate

4 weeks

Weekly visits for drug administration

Consolidation Chemotherapy

Patients receive methotrexate, cyclophosphamide, cytarabine, mercaptopurine, vincristine sulfate, and pegaspargase. Some patients also receive nelarabine and testicular radiotherapy

8 weeks

Bi-weekly visits for drug administration

Interim Maintenance Chemotherapy

Patients receive vincristine sulfate, escalating doses of methotrexate, and pegaspargase. Some patients receive high dose methotrexate with leucovorin rescue

8 weeks

Visits every 10 days for drug administration

Delayed Intensification Chemotherapy

Patients receive vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, methotrexate, nelarabine, cyclophosphamide, cytarabine, and thioguanine

8 weeks

Weekly visits for drug administration

Maintenance Chemotherapy

Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate, and nelarabine. Treatment repeats every 84 days until 2-3 years from the start of interim maintenance therapy

2-3 years

Monthly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Asparaginase
• Cyclophosphamide
• Daunorubicin Hydrochloride
• Dexamethasone
• Doxorubicin Hydrochloride
• Mercaptopurine
• Methotrexate
• Nelarabine
• Pegaspargase
• Prednisone
• Radiation Therapy
• Thioguanine
• Vincristine Sulfate

Trial Overview 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.

How Is the Trial Designed?

Group I: Group 0 Induction Therapy Experimental Treatment 6 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 Control 3 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 Control 4 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 Control 8 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 Control 9 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 Control 8 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 Control 8 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 Control 8 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 chemotherapy Active Control 9 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 Control 5 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 Control 5 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 Control 9 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 Control 5 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 Control 5 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 Control 5 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 Control 7 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 Control 4 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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

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Proven Efficacy and Safety Explore the safety and efficacy data supporting the treatment of acute lymphoblastic leukemia (ALL) with ONCASPAR® (pegaspargase).

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Efficacy and Safety of a Pegasparaginase-Based ... The DDGP regimen was well tolerated and showed statistically significant survival benefit over the SMILE regimen in treating newly diagnosed ENKL.

9. sciencedirect.com sciencedirect.com/science/article/pii/S2468124524000135

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Managing toxicities with asparaginase-based therapies in ... The best management of several key toxicities that can occur in adults treated with asparaginase including hepatotoxicity, pancreatitis, hypertriglyceridaemia, ...