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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 15 and over NCI CLB-9311 CALGB-9311

Objectives

I.  Study the role of lineage-specific therapies for minimal residual disease 
in the early intensification phase of treatment for adult acute lymphoblastic 
leukemia (ALL).

II.  Increase the precision in the CR rates using induction therapy identical 
to that used in protocols CLB-8811 and CLB-9111.

III.  Assess the safety and toxicity of monoclonal antibody anti-B4/blocked 
ricin administered by 7-day continuous infusion in patients with B-lineage ALL 
in first remission.

IV.  Assess the safety and toxicity of high-dose ARA-C given early in first 
remission in patients with non-B-lineage ALL.

V.  Evaluate minimal residual disease, using polymerase chain reaction 
methods, in patients with ALL who express the bcr-abl fusion gene, 
immunoglobulin heavy chain, or T-cell-receptor gene rearrangements before and 
after intensification and maintenance therapy.

Entry Criteria

Disease Characteristics:

Unequivocal diagnosis of acute lymphoblastic leukemia based on
FAB classification
  L1 and L2 only
     L3 may be eligible for protocol CLB-9251

  Cytochemical and immunologic studies consistent with ALL

  Acute undifferentiated leukemia eligible provided the
  following tests are negative:
     Myeloperoxidase or Sudan black reactivity
     Myeloid antigens (i.e., no M0 acute myeloid leukemia)

Simultaneous enrollment on the following protocols required:
  CLB-8364 (immunology)
     Sufficient bone marrow aspirate for immunophenotyping
     required
  CLB-8762 (molecular subtypes in Ph1-ALL)
  CLB-8763 (Ig and TCR gene rearrangements in ALL)

Simultaneous enrollment on protocol CLB-8461 (cytogenetics)
strongly encouraged

Prior/Concurrent Therapy:

No prior treatment (including steroids) for leukemia except:
  Hydroxyurea for rapidly progressing hyperleukocytosis allowed
     over no more than 72 hours prior to treatment
  Emergency leukapheresis
  One dose of cranial irradiation for CNS leukostasis

No prior treatment with or history of hypersensitivity to
murine monoclonal antibodies

Patient Characteristics:

Age:
  15 and over

Performance status:
  Not specified

Life expectancy:
  2 years (exclusive of ALL)

Hematopoietic:
  Not specified

Hepatic:
  Bilirubin less than 1.5 x normal (unless attributable to ALL;
     biopsy not required)

Renal:
  Creatinine less than 1.5 x normal (unless attributable to
     ALL; biopsy not required)

Cardiovascular:
  No uncontrolled or severe cardiovascular disease, including:
     MI within 6 months
     CHF

Other:
  Management at a medical facility with access to blood product
     support and adequately staffed to care for the severely
     neutropenic patient required throughout protocol therapy
  No active, uncontrolled bacterial, viral, or fungal infection
  No active, uncontrolled duodenal ulcer
  No serious medical illness that would limit survival to less
     than 2 years
  No psychiatric condition that would prevent informed consent
  No second malignancy within 5 years except:
     Curatively treated carcinoma in situ of the cervix
     Curatively treated basal cell carcinoma of the skin

Expected Enrollment

Accrual to the anti-B4-bR portion of the trial will be in 2 stages similar to 
a Phase II design:  if no more than 2 of the first 7 patients experience 
severe toxicity, an additional 24 patients will be treated on this arm; if a 
high percentage of patients is able to receive the planned therapy with a low 
percentage of severe toxicity, the treatment will be considered for further 
study.

Outline

Patients are designated as having B-lineage ALL (leukemic cells express the 
surface marker CD19) or non-B-lineage ALL (CD19 not expressed).  Treatment is 
identical for both groups except for Intensification II:  B-lineage ALL is 
treated with Anti-B4-bR on Regimen A and non-B-lineage ALL with high-dose 
cytarabine on Regimen B.  B-lineage patients who have active CNS disease or 
who previously received cranial irradiation for CNS disease omit 
Intensification II and proceed directly to Intensification III after recovery 
from Intensification I.  Patients with CNS disease at entry or while on study 
are managed according to Regimen C and, those with testicular leukemia 
according to Regimen D.

The following acronyms are used:
  Anti-B4-bR   Monoclonal Antibody B4/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
  DM           Dexamethasone, NSC-34521
  DNR          Daunorubicin, NSC-82151
  DOX          Doxorubicin, NSC-123127
  G-CSF        Granulocyte Colony Stimulating Factor (Amgen),
               NSC-614629
  HD           High Dose
  IT MTX       Intrathecal Methotrexate, NSC-740
  MP           Mercaptopurine, NSC-755
  PRED         Prednisone, NSC-10023
  TG           Thioguanine, NSC-752
  TMP/SMX      Trimethoprim/Sulfamethoxazole
  VCR          Vincristine, NSC-67574

INDUCTION:  5-Drug Combination Systemic Chemotherapy with Hematologic Toxicity 
Attenuation.  CTX/DNR/VCR/PRED/ASP with G-CSF.

INTENSIFICATION I:  3-Drug Combination Systemic Chemotherapy plus Single-Agent 
Intrathecal Chemotherapy Followed by 2-Drug Combination Systemic Chemotherapy. 
 CTX/ARA-C/MP; plus IT MTX; followed by VCR/ASP.

INTENSIFICATION II:

Regimen A (B-Lineage ALL):  Monoclonal Antibody Conjugate Therapy.  Anti-B4-bR.

Regimen B (Non-B-Lineage ALL):  Single-Agent High-Dose Systemic Chemotherapy.  
HD ARA-C.

INTENSIFICATION III:  3-Drug Combination Systemic Chemotherapy plus 
Single-Agent Intrathecal Chemotherapy Followed by 2-Drug Combination Systemic 
Chemotherapy.  CTX/ARA-C/MP; plus IT MTX; followed by VCR/ASP.

CNS PROPHYLAXIS/INTERIM MAINTENANCE:  Single-Agent Intrathecal Chemotherapy 
plus Radiotherapy plus 2-Drug Combination Systemic Chemotherapy.  IT MTX; plus 
cranial irradiation using Co60 or photons with energies of 4-6 MV; plus MP/MTX.

LATE INTENSIFICATION:  3-Drug Combination Systemic Chemotherapy followed by 
3-Drug Combination Systemic Chemotherapy.  DOX/VCR/DM; followed by 
CTX/ARA-C/TG.

MAINTENANCE:  2-Drug Combination Continuous Systemic Chemotherapy with Pulses 
of 2-Drug Combination Systemic Chemotherapy.  Daily MP/MTX with monthly pulses 
of VCR/PRED.

Regimen C (CNS Leukemia):  Radiotherapy plus (as indicated) Single-Agent 
Intrathecal Chemotherapy.  Cranial irradiation using equipment as in CNS 
Prophylaxis; plus IT MTX.

Regimen D (Testicular Leukemia):  Radiotherapy.  Testicular irradiation using 
equipment as in CNS Prophylaxis.

Szatrowski TP, Dodge RK, Reynolds C, et al.: Lineage specific treatment of adult patients with acute lymphoblastic leukemia in first remission with anti-B4-blocked ricin or high-dose cytarabine: Cancer and Leukemia Group B Study 9311. Cancer 97 (6): 1471-80, 2003.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Ted Paul Szatrowski, MD, Protocol chair(Contact information may not be current)		Ph: 212-746-3400