Trial Information

Treatment Protocol for Relapsed Anaplastic Large Cell Lymphoma of Childhood and Adolescence

OBJECTIVES:

Primary

- Improve the probability of event-free survival in children and adolescents with early
progression of anaplastic large cell lymphoma (ALCL) and/or relapse of ALCL with
CD3-positive immunophenotype treated with reinduction combination chemotherapy followed
by allogeneic or autologous stem cell transplantation.

- Determine whether a conditioning regimen comprising carmustine, etoposide phosphate,
cytarabine, and melphalan (BEAM) (without total body irradiation) for autologous stem
cell transplantation is an effective treatment for patients with relapsed CD3-negative
ALCL occurring after the intensive phase of treatment.

- Determine the impact of vinblastine in patients with late relapse of CD3-negative ALCL
who have not received vinblastine during frontline therapy.

Secondary

- Determine overall survival and treatment-related mortality in patients treated with
these regimens.

- Determine acute and long-term toxicity in patients treated with these regimens.

- Determine the rate of acute and chronic graft-vs-host disease in patients treated with
allogeneic stem cell transplantation.

OUTLINE: This is a multicenter, prospective, nonrandomized study. Patients are stratified
according to time from initial diagnosis to progression/relapse, immunophenotype of lymphoma
cells (CD3-positive + vs CD3-negative), stem cell donor availability (matched sibling donor
vs 9/10 or 10/10 matched unrelated donor), and vinblastine during frontline therapy (yes vs
no).

- Group 1 (early progression): Patients receive 1 course of ICM chemotherapy followed by
1 course of ICI chemotherapy.

- ICM chemotherapy: Patients receive methotrexate, cytarabine, and prednisolone
intrathecally (IT) on day 1, mitoxantrone hydrochloride IV over 5 hours on days 1
and 2, carboplatin IV continuously on days 2-5 and ifosfamide IV continuously on
days 2-6.

- ICI chemotherapy: Patients receive methotrexate, cytarabine, and prednisolone
intrathecally on day 1, idarubicin IV over 4 hours on days 1 and 2, carboplatin IV
continuously on days 2-5, and ifosfamide IV continuously on days 2-6.

Patients then proceed to allogeneic stem cell transplantation.

- Group 2 (relapsed disease and CD3-positive lymphoma cells): Patients are stratified
according to stem cell donor availability (yes vs no).

- Available donor: Patients receive 2 courses of CC chemotherapy and then proceed to
allogeneic stem cell transplantation.

- Unavailable donor : Patients receive 2 courses of CC chemotherapy comprising
dexamethasone orally or IV on days 1-5, vindesine IV on day 1, cytarabine IV over
3 hours on days 1 and 2, etoposide phosphate IV over 2 hours on days 3-5, and
methotrexate, cytarabine, and prednisolone IT on day 5. Patients then receive 1
course of CVA chemotherapy comprising oral lomustine on day 1, vinblastine IV on
days 1, 8, 15, and 22, and cytarabine IV over 1 hour on days 1-5. Patients undergo
leukapheresis for collection of autologous peripheral blood stem cells after the
first and/or second course of CC chemotherapy. Patients then proceed to autologous
stem cell transplantation.

- Group 3 (relapsed disease, CD3-negative immunophenotype, and received vinblastine
during frontline therapy): Patients receive 2 courses of CC chemotherapy and 1 course
of CVA chemotherapy as described above. Patients undergo leukapheresis for collection
of autologous peripheral blood stem cells (PBSC) after the first and/or second course
of CC chemotherapy. Patients then proceed to autologous stem cell transplantation.

- Group 4 (late relapse, CD3-negative immunophenotype, and did not receive vinblastine
during frontline therapy): Patients receive vinblastine IV once weekly for 24 months.
Patients with disease progression during or relapsed disease after vinblastine therapy
undergo treatment as in group 3.

- Autologous stem cell transplantation (SCT): Patients receive a conditioning regimen
comprising carmustine IV over 1 hour on day -7, etoposide phosphate IV over 1 hour and
cytarabine IV over 30 minutes on days -6 to -3, and melphalan IV over 15 minutes on day
-2. Patients undergo autologous SCT on day 0.

- Allogeneic SCT: Beginning 4-6 weeks after the start of the last chemotherapy course,
patients receive 1 of the following conditioning regimens based on age:

- Patients > 2 years of age undergo total body irradiation on days -7 to -5 and
receive thiotepa IV over 1 hour on day -4 and etoposide IV over 4 hours on day -3.
Patients undergo allogeneic SCT on day 0.

- Patients ≤ 2 years of age receive oral busulfan 4 times daily on days -8 to -5,
thiotepa IV over 1 hour twice on day -4, and etoposide phosphate IV over 4 hours
on day -3. Patients undergo allogeneic SCT on day 0.

Patients undergoing SCT from an unrelated donor also receive antithymocyte globulin IV over
4 hours on days -3 to -1.

All patients receive graft-versus-host (GVHD) prophylaxis as described below.

- GVHD prophylaxis: GVHD prophylaxis is administered as per donor status.

- Matched sibling donor: Patients receive cyclosporine IV over 2 hours or orally on
day -1 to 60 followed by a taper.

- 10/10 or 9/10 matched unrelated donor: Patients receive cyclosporine IV over 2
hours or orally on days -1 to 100 followed by a taper, methotrexate IV on days 1,
3, and 6, and leucovorin calcium IV on days 2, 4, and 7.

- Mismatched donor: Patients do not receive GVHD prophylaxis, however, CD3-positive
lymphocytes are extracted from donor stem cells.

After completion of study treatment, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 96 patients will be accrued for this study.