Advertisement

Topics

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia

2014-08-27 03:41:15 | BioPortfolio

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. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating T-cell acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating young patients with newly diagnosed T-cell acute lymphoblastic leukemia.

Description

OBJECTIVES:

Primary

- Compare the relative safety and efficacy of augmented Berlin-Frankfurt-Münster-86 multiagent chemotherapy with or without nelarabine in younger patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL).

- Compare the relative safety and efficacy of interim maintenance therapy comprising high-dose methotrexate (with leucovorin calcium rescue) and mercaptopurine vs escalating-dose methotrexate ( without leucovorin calcium rescue) and pegaspargase in these patients.

Secondary

- Determine the relative safety and efficacy of withholding radiotherapy in patients with low -risk T-ALL and administering prophylactic cranial radiotherapy in patients with intermediate- or high-risk T-ALL.

OUTLINE: This is a randomized, controlled, factorial-group, multicenter study.

- Induction therapy (weeks 1-5): Patients receive cytarabine intrathecally (IT) on day 1; vincristine IV and daunorubicin hydrochloride IV on days 1, 8, 15, and 22; prednisone IV or orally twice daily on days 1-28; pegaspargase intramuscularly (IM) on day 4, 5, OR 6; and methotrexate (MTX) IT on days 8 and 29*. Patients with Down syndrome (DS) also receive oral leucovorin calcium at 48 and 60 hours after each MTX dose.

After completion of induction therapy, patients undergo risk assessment. Patients with M1 marrow and minimal residual disease (MRD) < 1% (defined as low- and intermediate-risk) proceed to consolidation therapy at day 36 or when blood counts recover (whichever occurs later). Patients with M2 marrow (5-25% blasts) and/or MRD ≥ 1% (defined as high-risk) proceed to consolidation therapy as soon as possible (i.e., they should not wait until day 36 or for blood counts to recover). Patients with M3 marrow (≥ 25% blasts) (defined as induction failure) proceed to consolidation therapy as soon as possible.

NOTE: *Patients with CNS3 disease also receive MTX IT on days 15 and 22.

- Consolidation therapy (weeks 6-13): During the safety phase portion of the study, patients with low-risk or intermediate-risk disease are randomized to arms I or III. Patients with high-risk disease are randomized to arms I, II, III, or IV. During the efficacy phase portion of the study, patients with low-risk disease are randomized to arms I and III. Patients with intermediate-risk or high-risk disease are randomized to arms I, II, III, or IV. The safety phase ends when the first 20 high-risk patients to receive nelarabine have been evaluated. Patients with DS are nonrandomly assigned to arm I. Patients with induction failure are nonrandomly assigned to arm IV.

- Arm I: Patients receive MTX IT on days 1, 8, 15, and 22*; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; oral mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43 and 50; and pegaspargase IM on days 15 and 43. Patients with DS also receive oral leucovorin calcium at 48 and 60 hours after each MTX dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic cranial radiotherapy (CRT) (1,200 cGy/dose) once daily on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT.

NOTE: *Patients with CNS3 disease omit MTX IT on days 15 and 22; patients with high-risk disease omit MTX IT on day 1 and add an extra dose at day 29.

- Arm II: Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; MTX IT on days 15, 22*, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV or SC on days 8-11, 15-18, 50-53 and 57-60; oral mercaptopurine on days 8-21 and 50-63; vincristine IV on days 22, 29, 64, and 71; and pegaspargase IM 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. Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT once daily on days 22-28 and 29-35.

NOTE: *Patients with CNS3 disease omit MTX IT on day 22.

- Arm III: Patients receive MTX, cyclophosphamide, cytarabine, mercaptopurine, vincristine, and pegaspargase as in arm I. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy as in arm I.

- Arm IV: Patients receive nelarabine, MTX, cyclophosphamide, cytarabine, mercaptopurine, vincristine, and pegaspargase as in arm II. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy as in arm II.

Once blood counts recover, patients proceed to interim maintenance therapy according to their randomized/assigned arm. Patients not achieving M1 marrow by the end of consolidation therapy are removed from the study.

- Interim maintenance therapy (weeks 14-21 for arms I and III; weeks 17-24 for arms II and IV):

- Arm I: Patients receive vincristine IV and escalating doses of MTX IV on days 1, 11, 21, 31, and 41; pegaspargase* IM on days 2 and 22; and MTX IT on days 1 and 31. Patients with DS also receive oral leucovorin calcium 48 and 60 hours after each MTX IT dose.

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.

- Arm II: Patients receive vincristine, escalating doses of MTX, pegaspargase, and MTX IT as in arm I.

- Arm III: Patients receive high-dose methotrexate (HDMTX) IV over 24 hours and vincristine IV on days 1, 15, 29, and 43; oral mercaptopurine on days 1-56; and MTX IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or orally once every 6 hours for 3 doses.

- Arm IV: Patients receive HDMTX, vincristine, mercaptopurine, MTX IT, and leucovorin calcium as in arm III.

Once blood counts recover, patients proceed to delayed instensification therapy according to their randomized/assigned arm.

- Delayed intensification therapy (weeks 22-30 for arms I and III; weeks 25-33 for arms II and IV):

- Arm I: Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or orally twice daily 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 over 15 minutes on days 1, 8, and 15; pegaspargase IM on day 4, 5, OR 6, AND day 43; MTX IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV or SC on days 29-32 and 36-39; and oral thioguanine on days 29-42. Patients with DS also receive oral leucovorin calcium at 48 and 60 hours after each MTX dose.

- Arm II: Patients receive vincristine IV on days 1, 8, 15, and 50; dexamethasone IV or orally twice daily 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 over 15 minutes on days 1, 8, and 15; pegaspargase IM on day 4, 5, OR 6 AND day 50; MTX 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 or SC on days 36-39 and 43-46; and oral thioguanine on days 36-49.

- Arm III: Patients receive vincristine, dexamethasone, doxorubicin hydrochloride, pegaspargase, MTX IT, cyclophosphamide, cytarabine, and thioguanine as in arm I. Patients with intermediate- or high-risk disease (CNS1 or CNS2 disease) undergo prophylactic CRT (1,200 cGy/dose) once daily on days 50-54 and 57-59.

- Arm IV: Patients receive vincristine, dexamethasone, doxorubicin hydrochloride, pegaspargase, MTX IT, nelarabine, cyclophosphamide, cytarabine, and thioguanine as in arm II. Patients with intermediate- or high-risk disease (CNS 1 or CNS2 disease) undergo prophylactic CRT on days 50-54 and 57-59.

All patients with CNS3 disease at diagnosis undergo CRT (1,800cGy/dose) once daily on days 50-54 and 57-61.

Once blood counts recover, patients proceed to maintenance therapy according to their randomized/assigned arm.

- Maintenance therapy (week 31 until the end of therapy for arms I and III; weeks 34-69 for arms II and IV):

- Arm I: Patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily on days 1-5, 29-33, and 57-61; oral mercaptopurine once daily on days 1-84; oral MTX on days 8, 15, 22, 29*, 36, 43, 50, 57, 64, 71, and 78; and MTX 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) and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys).

NOTE: *Patients with low-risk disease receive MTX IT, instead of oral MTX, on day 29 during the first 4 courses of therapy.

- Arm II: Patients receive vincristine IV on days 1 and 57; oral dexamethasone on days 1-5 and 57-61; oral mercaptopurine once daily on days 1-84; oral MTX on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; MTX IT on day 1; and nelarabine IV over 60 minutes on days 29-33. Treatment (that includes nelarabine) repeats every 84 days for 3 courses. Patients then receive treatment (without nelarabine) as follows: vincristine IV on days 1 and 57; oral dexamethasone on days 1-5, 29-33, and 57-61; oral mercaptopurine on days 1-84; oral MTX on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and MTX IT on day 1. 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) and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys).

- Arm III: Patients receive vincristine, dexamethasone, mercaptopurine, oral MTX*, and MTX IT as in arm I. 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) and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys).

NOTE: *Patients with low-risk disease receive MTX IT, instead of oral MTX, on day 29 during the first 4 courses of therapy.

- Arm IV: Patients receive vincristine, dexamethasone, mercaptopurine, oral MTX, MTX IT, and nelarabine as in arm II. Patients then receive treatment (without nelarabine) as follows: vincristine, dexamethasone, mercaptopurine, oral MTX, and MTX 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) and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys).

After completion of study therapy, patients are followed periodically for at least 10 years.

PROJECTED ACCRUAL: A total of 1,380 patients will be accrued for this study.

Study Design

Allocation: Randomized, Control: Active Control, Primary Purpose: Treatment

Conditions

Leukemia

Intervention

cyclophosphamide, cytarabine, dexamethasone, doxorubicin hydrochloride, leucovorin calcium, mercaptopurine, methotrexate, nelarabine, pegaspargase, thioguanine, vincristine sulfate, radiation therapy

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock
Arkansas
United States
72205

Status

Recruiting

Source

National Cancer Institute (NCI)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:41:15-0400

Clinical Trials [3427 Associated Clinical Trials listed on BioPortfolio]

Dexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

RATIONALE: Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin calcium, work in different ways to stop cancer cells from dividing so they stop growi...

LBL-2016 for Children or Adolescents in China

The outcomes of children with lymphoblastic lymphoma (LBL) in China in our previous study were not unexpected. In this study, through further modification treatment protocols and strengthe...

Azacitidine and Combination Chemotherapy in Treating Infants With Acute Lymphoblastic Leukemia and MLL Gene Rearrangement

This pilot trial studies the side effects of azacitidine and combination chemotherapy in infants with acute lymphoblastic leukemia and myeloid/lymphoid or mixed-lineage leukemia (MLL) gene...

Prednisolone or Dexamethasone Combined With Chemotherapy in Treating Young Patients With Newly Diagnosed Lymphoblastic Lymphoma

RATIONALE: Drugs used in chemotherapy, such as prednisolone and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them fr...

Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: ...

PubMed Articles [2723 Associated PubMed Articles listed on BioPortfolio]

Phase 2 trial of bortezomib in combination with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with bortezomib, rituximab, methotrexate, and cytarabine for untreated mantle cell lymphoma.

Although the outcomes of patients with mantle cell lymphoma (MCL) have improved, there is still no cure. Bortezomib has a 33% response rate in relapsed/refractory MCL and has shown additive and/or syn...

Thiotepa, Etoposide, Cyclophosphamide, Cytarabine, and Melphalan (TECAM) Conditioning Regimen for Autologous Stem Cell Transplantation in Lymphoma.

High-dose chemotherapy and autologous stem cell transplantation (ASCT) is the current standard of care for relapsed non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Conditioning regimens with hig...

Two multicenter Phase I randomized trials to compare the bioequivalence and safety of a generic doxorubicin hydrochloride liposome injection with Doxil or Caelyx in advanced ovarian cancer.

To compare the pharmacokinetic bioequivalence and safety of a generic pegylated liposomal doxorubicin formulation (SPIL DXR hydrochloride liposome injection) with that of the reference products, Caely...

Cyclophosphamide's addition in relapsed/refractory multiple myeloma patients with biochemical progression during lenalidomide-dexamethasone treatment.

The aim of this study was to evaluate the addition of Cyclophosphamide in relapsed-refractory Multiple Myeloma patients (RRMM) who experienced biochemical relapse or progression without CRAB, during t...

Impact of homologous recombination deficiency biomarkers on outcomes in patients with triple-negative breast cancer treated with doxorubicin-based adjuvant chemotherapy (SWOG S9313).

Homologous recombination deficiency (HRD) causing alterations have been reported in triple-negative breast cancer (TNBC). We hypothesized that TNBCs with HRD alterations might be more sensitive to ant...

Medical and Biotech [MESH] Definitions

The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.

Congener of CYTARABINE that is metabolized to cytarabine and thereby maintains a more constant antineoplastic action.

A naphthalene derivative and CALCIMIMETIC AGENT that increases the sensitivity of PARATHYROID GLAND calcium-sensing receptors to serum calcium. This action reduces parathyroid hormone secretion and decreases serum calcium in the treatment of PARATHYROID DISEASES.

A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)

Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.

More From BioPortfolio on "Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Head and neck cancers
Cancer can occur in any of the tissues or organs in the head and neck. There are over 30 different places that cancer can develop in the head and neck area. Mouth cancers (oral cancers)  - Mouth cancer can develop on the lip, the tongue, the floor...

Pharmacy
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Cancer Disease
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...


Searches Linking to this Trial