Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Study for Treatment of Cancer in Children With Ataxia-telangiectasia

This study has been completed.
Sponsor:
Collaborators:
Children's Hospital of Philadelphia
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00187057
First received: September 12, 2005
Last updated: August 26, 2013
Last verified: August 2013
  Purpose

This is a pilot/feasibility study designed to investigate the feasibility of treating children with Ataxia-Telangiectasia (A-T) and cancer with regimens nearly as intense as non-A-T patients with cancer would receive.


Condition Intervention
Ataxia-Telangiectasia
Drug: vinblastine, vincristine, prednisone, daunorubicin
Drug: doxorubicin, methotrexate, cyclophosphamide, L-asparaginase
Drug: etoposide, cytarabine, mercaptopurine
Drug: dexamethasone, procarbazine
Procedure: chemotherapy, intrathecal chemotherapy, steroid therapy

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study I for Treatment of Cancer in Children With Ataxia-Telangiectasia

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • To determine the feasibility of delivering modified intensive chemotherapy to children with A-T who present with cancer. [ Time Frame: The completion of treatment ] [ Designated as safety issue: Yes ]

Enrollment: 6
Study Start Date: September 2002
Study Completion Date: June 2013
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1
Acute Lymphoblastic Leukemia (ALL) Low Risk
Drug: vinblastine, vincristine, prednisone, daunorubicin
See Detailed Description section for details of treatment interventions.
Drug: doxorubicin, methotrexate, cyclophosphamide, L-asparaginase
See Detailed Description section for details of treatment interventions.
Drug: etoposide, cytarabine, mercaptopurine
See Detailed Description section for details of treatment interventions.
Drug: dexamethasone, procarbazine
See Detailed Description section for details of treatment interventions.
Procedure: chemotherapy, intrathecal chemotherapy, steroid therapy
See Detailed Description section for details of treatment interventions.
2
Acute Lymphoblastic Leukemia (ALL) - High Risk
Drug: vinblastine, vincristine, prednisone, daunorubicin
See Detailed Description section for details of treatment interventions.
Drug: doxorubicin, methotrexate, cyclophosphamide, L-asparaginase
See Detailed Description section for details of treatment interventions.
Drug: etoposide, cytarabine, mercaptopurine
See Detailed Description section for details of treatment interventions.
Drug: dexamethasone, procarbazine
See Detailed Description section for details of treatment interventions.
Procedure: chemotherapy, intrathecal chemotherapy, steroid therapy
See Detailed Description section for details of treatment interventions.
3A
B-Cell Non-Hodgkins Lymphoma (Group A)
Drug: vinblastine, vincristine, prednisone, daunorubicin
See Detailed Description section for details of treatment interventions.
Drug: doxorubicin, methotrexate, cyclophosphamide, L-asparaginase
See Detailed Description section for details of treatment interventions.
Drug: etoposide, cytarabine, mercaptopurine
See Detailed Description section for details of treatment interventions.
Drug: dexamethasone, procarbazine
See Detailed Description section for details of treatment interventions.
Procedure: chemotherapy, intrathecal chemotherapy, steroid therapy
See Detailed Description section for details of treatment interventions.
3B
B-Cell Non-Hodgkins Lymphoma (Group B)
Drug: vinblastine, vincristine, prednisone, daunorubicin
See Detailed Description section for details of treatment interventions.
Drug: doxorubicin, methotrexate, cyclophosphamide, L-asparaginase
See Detailed Description section for details of treatment interventions.
Drug: etoposide, cytarabine, mercaptopurine
See Detailed Description section for details of treatment interventions.
Drug: dexamethasone, procarbazine
See Detailed Description section for details of treatment interventions.
Procedure: chemotherapy, intrathecal chemotherapy, steroid therapy
See Detailed Description section for details of treatment interventions.
4
Hodgkins Disease
Drug: vinblastine, vincristine, prednisone, daunorubicin
See Detailed Description section for details of treatment interventions.
Drug: doxorubicin, methotrexate, cyclophosphamide, L-asparaginase
See Detailed Description section for details of treatment interventions.
Drug: etoposide, cytarabine, mercaptopurine
See Detailed Description section for details of treatment interventions.
Drug: dexamethasone, procarbazine
See Detailed Description section for details of treatment interventions.
Procedure: chemotherapy, intrathecal chemotherapy, steroid therapy
See Detailed Description section for details of treatment interventions.

  Hide Detailed Description

Detailed Description:

Approximately 10-30% of A-T patients will develop a malignancy during their lifetime. The vast majority of these cancers are of lymphoid origin. There is no consensus regarding the optimal strategy for treating children with A-T who develop hematopoietic malignancies. Historically, many of these children have been treated with therapy that is much less intensive than the conventional approach for non-A-T patients with similar malignancies during the corresponding treatment era. Although these less intensive approaches may have stemmed from perceptions that these children would not tolerate intensive therapy, there is in fact no data to suggest that these children cannot tolerate intensive therapy. However, it is clear that children with A-T require a modification in certain components of intensive therapy.

To provide children with A-T and either ALL or malignant lymphoma the best chance for a cure, we propose to use modern therapeutic strategies with minimal modifications which address the unique toxicity profile encountered in treating children with A-T.

Secondary objectives include:

  • To clinically and biologically characterize the malignancies occurring in children with A-T (usually malignant lymphoma or ALL). This will include in vitro drug sensitivity screening.
  • To study chemotherapy-induced DNA damage in children with A-T.

Detailed Description of Treatment Plan:

  • Acute Lymphoblastic Leukemia (ALL) Low Risk:

Induction:

Prednisone 40 mg/m2/day PO days 1-28

Vinblastine 6 mg/m2/dose IV day 8

Vincristine 1.5 mg/m2/dose days 1, 15

Daunomycin 20 mg/m2/week IV days 1,15

Asparaginase 10,000 U/m2/dose IM days 2, 4, 6, 8, 10, 12

VP-16 225 mg/m2/dose Days 22, 25, 29

Ara-C 300 mg/m2/dose Days 22, 25, 29

All patients will receive CNS therapy with triple intrathecal therapy on days 1, 22 and 43 of induction treatment, dose age adjusted.

Consolidation:

Methotrexate 2 mg/m2 IV day 43 and 50 and mercaptopurine 75 mg/m2 days 43-56.

Continuation therapy (120 weeks):

Week:

  1. 6-MP + MTX
  2. 6-MP + MTX
  3. 6-MP + MTX
  4. Dex + VCR
  5. 6-MP + MTX
  6. 6-MP + MTX
  7. 6-MP + HDMTX
  8. Dex + VCR
  9. 6-MP + MTX
  10. 6-MP + MTX
  11. 6-MP + MTX
  12. Dex + VCR
  13. 6-MP + MTX
  14. 6-MP + MTX
  15. 6-MP + HDMTX

This sequence will be repeated through week 52 after which 6-MP + MTX will be given weekly to complete 120 weeks. IT MHA (MTX, hydrocortisone, Ara-C) on weeks 1, 2, 7, and 15 and then every 4-8 weeks depending on CNS status.

Dosages, Schedules and Routes:

6-MP 75 mg/m2 PO; daily x 7

MTX 40 mg/m2 IM or IV; q (every) week;

Dex 6 mg/m2 PO; in 3 divided doses daily x 7

VCR 1.5 mg/m2 IV (max. 2.0 mg)

HDMTX 2 g/m2 IV over 2 hours, every 8 weeks

Reinduction:

Reinduction therapy (weeks 16-21). Reinduction therapy (same as initial induction treatment minus dose 2 and 3 of VP16 +ara-C and minus day 22 intrathecal therapy) will be given after bone marrow examination on week 15 confirms complete remission.

  • Acute Lymphoblastic Leukemia (ALL) - High Risk

Induction:

Prednisone 40 mg/m2/day PO) divided in 3 doses days 1-28

Vinblastine 6 mg/m2/dose IV day 8

Vincristine 1.5 mg/m2/dose days 1, 15

Daunomycin 20 mg/m2/week IV days 1, 15

Asparaginase 10,000 U/m2/dose IM days 2, 4, 6, 8, 10, 12, (15, 17, 19)

VP16 225 mg/m2/dose days 22, 25, 29

Ara-C 300 mg/m2/dose days 22,25,29

All patients will receive triple IT therapy on days 1, 22 and 43 of induction with additional IT therapy on days 8 and 15 if CNS leukemia (CNS 2 or CNS 3) is present at diagnosis. If required, for patients with CNS 2 and 3 at diagnosis, IT therapy will continue until 2 consecutive CSF studies are normal (i.e., days 29 and 36).

Consolidation:

HDMTX 2 mg/m2 IV day 43 and 50

6 MP 75 mg/m2 PO days 43-56

Continuation Therapy (120 weeks):

Week:

  1. Dex + VCR
  2. VP-16 + CTX
  3. 6-MP + MTX
  4. MTX + Ara-C
  5. Dex + VCR
  6. VP-16 + CTX
  7. 6-MP + HDMTX
  8. 6-MP + MTX
  9. Dex + VCR
  10. VP-16 + CTX
  11. 6-MP + MTX
  12. MTX + Ara-C
  13. Dex + VCR
  14. VP-16 + CTX
  15. 6-MP + HDMTX

These sequences will be repeated through week 52, after which 6MP/MTX will be given weekly to complete 120 weeks.

IT MHA (MTX, hydrocortisone, Ara-C) on weeks 1, 2, 7, and 15 and then every 4-8 weeks depending on CNS status and risk status.

Dosages, Schedules and Routes:

VP 16 225 mg/m2 IV once a week

Cyclophosphamide 300 mg/m2 IV (with MESNA) once a week in addition to the 6 hour IV hydration

6-MP 75 mg/m2 PO; daily x 7

MTX 40 mg/m2 IM or IV once a week

Ara-C 300 mg/m2 IV push; once a week

Dex 8 mg/m2/day PO; in 3 divided doses daily x 7

VCR 1.5 mg/m2 IV push (max. 2.0 mg)

HDMTX 2 g/m2 IV over 2 hours; every 8 weeks x 7

  • B-Cell Non-Hodgkins Lymphoma

Overview - the chemotherapy regimen used varies with grouping based on extent of disease

Group A

Induction (COPAD x 2 cycles):

Cyclophosphamide 500 mg/m2/day (divided every 12 hour) IV (with MESNA) Day 1, 2, 3

Vincristine 2.0 mg/m2 IV Day 1

Vinblastine 6 mg/m2 IV Day 6

Prednisone 60 mg/m2/day (bid) PO Day 1-5

Adriamycin 50 mg/m2 (over 6 hrs) IV Day 1

G-CSF 5 mcg/kg/day until count recovery.

Group B

COP Induction:

Cyclophosphamide 300 mg/m2 IV (divided every 12 hours) IV (with MESNA) Day 1

Vincristine 1.0 mg/m2 IV Day 1

Prednisone 60 mg/m2/day (divided bid) PO days 1-7

CNS Therapy Intrathecal Day 1 - dose age adjusted

COPAD-M3 Induction x 2 cycles:

Vinblastine 6 mg/m2 IV Day 1

HD MTX 3 mg/m2 IV over 3 hours Day 1 with leucovorin rescue

CNS Therapy intrathecal each age adjusted Day 2, 6

Cyclophosphamide 500 mg/m2/day (second course 1 mg/m2/day) IV (with MESNA) Day 2, 3, 4

Adriamycin 50 mg/m2 IV Day 2

Prednisone 60 mg/m2 (divided bid) PO Day 1-5

G-CSF 5 mcg/kg/day until count recovery

CYM Consolidation x 2 cycles:

HD MTX 3 mg/m2 IV over 3 hours Day 1 with leucovorin rescue

Ara-C 100 mg/m2/day CI/IV (x 5 days) Day 2-6

CNS Therapy intrathecal each age adjusted Day 2 and 7

Maintenance:

Prednisone 60 mg/m2/day (divided bid) PO Day 1-5

HDMTX 3 mg/m2 IV over 3 hours Day 1 with leucovorin rescue

CNS Therapy intrathecal each age adjusted Day 2

Cyclophosphamide 500 mg/m2/day IV (with MESNA) Day 2, 3

Adriamycin 50 mg/m2 IV Day 3

Vincristine 2 mg/m2 IV Day 1

G-CSF 5 mcg/kg/day until count recovery

  • Limited Stage Non-Hodgkins Lymphoma

Induction:

Vincristine 2 mg/m2 IV days 1, 22 (maximum dose 2 mg)

Vinblastine 6 mg/m2 IV, day 8

Prednisone 40 mg/m2/day in 3 divided doses x 28 days

Adriamycin 30 mg/m2/day IV over one hour days 1 and 22

Cyclophosphamide 750 mg/m2/day IV days 1 and 22

Triple IT chemotherapy for participants with head and neck primary tumors on days 1, 8, 22. Each dose age adjusted.

Consolidation - start day 43:

Adriamycin 30 mg/m2 by IV

Cyclophosphamide 750 mg/m2

Prednisone 40 mg/m2 in 3 divided doses x 5 days

Vincristine 2.0 mg/m2 (max. 2.0 mg) by IV

Triple IT chemotherapy for head and neck primaries on days 43 and 64.

Maintenance:

Maintenance chemotherapy will be administered only to patients with lymphoblastic lymphoma and will consist of 24 weeks of chemotherapy with oral daily 6-MP and weekly oral methotrexate (and TIT every 6 weeks for patients with head and neck primaries) after induction/consolidation.

  • Hodgkins Disease

Participants with favorable disease will receive VAMP chemotherapy:

VAMP chemotherapy doses and schedule:

Vinblastine 6 mg/m2, IV day 1, 15 (maximum dosage: 10 mg)

Adriamycin 25 mg/m2, IV day 1, 15

Methotrexate 20 mg/m2, IV day 1, 15

Prednisone 40 mg/m2 PO day 1-14 divided into 3 daily doses

Repeat cycle every 28 days, total number of cycles = 6 (NO RADIATION THERAPY)

Participants with unfavorable disease will receive VAMP and COP:

VAMP chemotherapy doses (cycles 1, 3, 5, 7)

Vinblastine 6 mg/m2 IV day 1, 15

Adriamycin 25 mg/m2 IV day 1,15

Methotrexate 20 mg/m2 IV day 1, 15

Prednisone 40 mg/m2 (divided into 3 daily doses) PO day 1-14

COP chemotherapy doses (cycles 2, 4, 6, 8)

Cyclophosphamide 600 mg/m2 IV (with MESNA) day 1, 8

Vincristine 1.4 mg/m2 IV day 1,8 (max dose 2 mg)

Procarbazine 100 mg/m2 PO day 1-14

(NO RADIATION THERAPY)

  Eligibility

Ages Eligible for Study:   up to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have a diagnosis of Ataxia-Telangiectasia (A-T).
  • Patient must have a diagnosis of either acute lymphoblastic leukemia (ALL) or lymphoma (non-Hodgkin lymphoma or Hodgkin's disease).
  • Patients with other malignancies (solid tumors, rare malignancies, or relapsed hematopoietic malignancies) will be eligible for the biologic studies of this protocol; they will receive best clinical management chemotherapy.
  • Patients do not have to be previously untreated. If prior chemotherapy has already started (up through induction), therapy will be continued according to protocol at a clinically appropriate time point.

Exclusion Criteria:

  • Patients who do not have a diagnosis of Ataxia Telangiectasia (A-T).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00187057

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Children's Hospital of Philadelphia
Investigators
Principal Investigator: John T. Sandlund, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
Publications:
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00187057     History of Changes
Other Study ID Numbers: AT-1
Study First Received: September 12, 2005
Last Updated: August 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Ataxia
alphafetoprotein

Additional relevant MeSH terms:
Ataxia
Ataxia Telangiectasia
Telangiectasis
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebellar Ataxia
Cerebellar Diseases
DNA Repair-Deficiency Disorders
Dyskinesias
Genetic Diseases, Inborn
Immune System Diseases
Immunologic Deficiency Syndromes
Metabolic Diseases
Nervous System Diseases
Neurocutaneous Syndromes
Neurologic Manifestations
Signs and Symptoms
Spinocerebellar Ataxias
Vascular Diseases
Asparaginase
Cyclophosphamide
Daunorubicin
Dexamethasone
Methotrexate
Procarbazine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on November 20, 2014