Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III, Phase II Treatment Completed under 21 at relapse NCI POG-9410 POG-SIMAL-8, POG-9410

Objectives

I.  Assess the toxicity and feasibility of intensive re-induction and 
reconsolidation chemotherapy in children with non-T, non-B acute lymphoblastic 
leukemia in first bone marrow relapse.

II.  Assess, in those patients who achieve a complete response (CR) after 2 
consolidation courses, the toxicity and feasibility of marrow-ablative 
chemoradiotherapy and autologous bone marrow rescue using marrow purged with 
monoclonal antibody B4 conjugated with blocked ricin and with 
cyclosporine-induced syngeneic graft versus host disease.

III.  Estimate the relapse rate among children who achieve CR.

Entry Criteria

Disease Characteristics:

Non-T-, non-B-cell acute lymphoblastic leukemia in first marrow relapse
  Greater than 25% blasts in marrow (M3)
  CD19-positive blasts at relapse

Concomitant or prior extramedullary relapse eligible

Prior/Concurrent Therapy:

Prior cumulative anthracycline dose no greater than 360 mg/sqm

Patient Characteristics:

Age:
  Under 21 at relapse

Performance status:
  Not specified

Hepatic:
  Bilirubin less than 1.5 x ULN
  Transaminases less than 4 x ULN

Renal:
  Creatinine less than 2 x ULN

Cardiovascular:
  LVEF greater than 50%

Pulmonary:
  FVC and FEV1 greater than 60% of predicted

Other:
  No second malignancy
  No pregnant or nursing women
  Effective contraception required of fertile patients

Expected Enrollment

25 patients will be entered; 15 patients are expected to be eligible for 
transplantation.  Accrual will be suspended for occurrence of 3 incidents of 
any fatal toxicity or 2 incidents of the same fatal toxicity.

Outline

Following Induction and Consolidation I and II, patients in CR undergo 
myeloablative chemoradiotherapy and hematopoietic rescue:  patients with an 
identical or 1-antigen-only-mismatched sibling donor are treated on Regimen A 
with allogeneic marrow; those without a suitable donor are treated on Regimen 
B with autologous marrow purged with Anti-B4-bR and with CYSP-induced 
syngeneic graft-versus-host disease.  Prior to marrow ablation/rescue, 
patients who developed CNS relapse at any time during protocol treatment and 
those with CNS disease at entry that has not previously been irradiated 
receive boost CNS irradiation.

The following acronyms are used:
  Anti-B4-bR    Monoclonal Antibody Anti-B4 conjugated with Blocked Ricin,
                NSC-639185
  ARA-C         Cytarabine, NSC-63878
  ASP           Asparaginase, NSC-109229 (E. coli) or NSC-106977 (Erwinia)
  CF            Leucovorin calcium, NSC-3590
  CTX           Cyclophosphamide, NSC-26271
  CYSP          Cyclosporine, NSC-290193
  DOX           Doxorubicin, NSC-123127
  G-CSF         Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629
  GVHD          Graft Versus Host Disease
  HC            Hydrocortisone, NSC-10483
  IDA           Idarubicin, NSC-256439
  IFF           Ifosfamide, NSC-109724
  Mesna         Mercaptoethane sulfonate, NSC-113891
  MTX           Methotrexate, NSC-740
  PRED          Prednisone, NSC-10023
  TBI           Total-Body Irradiation
  TIT           Triple Intrathecal Therapy:  MTX/HC/ARA-C
  TMP-SMX       Trimethoprim-sulfamethoxazole
  VCR           Vincristine, NSC-67574
  VP-16         Etoposide, NSC-141540

INDUCTION:  4-Drug Combination Systemic Chemotherapy plus 3-Drug Intrathecal 
Therapy.  DOX; PRED; VCR; ASP; plus TIT.

CONSOLIDATION I:  2-Drug Combination Systemic Chemotherapy.  VP-16; IFF/Mesna.

CONSOLIDATION II:  2-Drug Combination Systemic Chemotherapy.  ARA-C; IDA.

CNS BOOST RADIOTHERAPY:  Cranial irradiation using photon energies of at least 
4 MV.

MARROW ABLATION/HEMATOPOIETIC RESCUE.

Regimen A (Allogeneic Marrow):  Myeloablative High-Dose Chemoradiotherapy plus 
Single-Agent Intrathecal Chemotherapy
followed by Hematopoietic Rescue plus GVHD Prophylaxis.  TBI with testicular 
boost using photons with energies of at least 4 MV; High-Dose VP-16; High-Dose 
CTX/Mesna; plus IT MTX; followed by allogeneic marrow; G-CSF; plus MTX/CF/CYSP.

Regimen B (Purged Autologous Marrow):  Myeloablative High-Dose 
Chemoradiotherapy plus Single-Agent Intrathecal Chemotherapy followed by 
Hematopoietic Rescue plus Induced Syngeneic GVHD.  Chemoradiotherapy and 
Intrathecal Therapy identical to Regimen A; followed by autologous marrow 
purged with Anti-B4-bR; G-CSF; plus CYSP.

Trial Contact Information

Trial Lead Organizations

Pediatric Oncology Group

Eric Sandler, MD, Protocol chair		Ph: 904-390-3793 Email: esandler@nemours.org