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, Phase I Treatment Closed 15 to 60 DUT-KWF-CKVO-8901 EU-90001

Objectives

I.  Assess the toxicity and determine the MTD of dimethylbusulfan/etoposide as 
marrow-ablative chemotherapy followed by autologous bone marrow 
transplantation.
II.  Assess the efficacy of this combination in inducing complete and partial 
remissions in adults with AML in first relapse.
III.  Assess, after establishing the MTD, the efficacy of this regimen in 
inducing and/or maintaining second remissions.

Entry Criteria

Disease Characteristics:

Cytologically or histologically confirmed AML (FAB M1-M6) in
first relapse

Adequate first remission bone marrow must have been
cryopreserved (at least 1 x 10 to the eighth but preferably 2
x 10 to the eighth nucleated bone marrow cells/kg body weight)

At least 3 months must have elapsed between cryopreservation
of remission marrow and date of relapse

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No prior chemotherapy for relapsed AML

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior radiotherapy for relapsed AML

Surgery:
  Not specified

Patient Characteristics:

Age:
  15 to 60

Performance status:
  WHO 0-2

Hematopoietic:
  Not specified

Hepatic:
  No severe hepatic disease

Renal:
  No severe renal disease

Cardiovascular:
  No severe cardiac disease

Pulmonary:
  No severe pulmonary disease

Other:
  No severe neurologic or metabolic disease
  No HIV-positive patients
  Adequate supportive care possible (e.g., HLA-identical
     donor available in case of sensitization)

  No other active malignant disease except secondary acute
  leukemia following cured Hodgkin's disease or other
  neoplasm or other secondary leukemia, provided they were
  not treated with chemotherapy

Expected Enrollment

A maximum of 18 patients will be entered during the Phase I portion of the 
study and at least 20 patients will then be treated at the MTD.

Outline

Nonrandomized study.  All patients receive Reinduction on Regimen A; those who 
achieve CR or PR and are eligible for autologous transplant proceed to Regimen 
B.
Regimen A:  2-Drug Combination Chemotherapy.  Cytarabine, ARA-C, NSC-63878; 
Mitoxantrone, DHAD, NSC-301739.
Regimen B:  2-Drug Combination Chemotherapy followed by Bone Marrow Therapy.  
Dimethylbusulfan, DMB; Etoposide, VP-16, NSC-141540; followed by Autologous 
Bone Marrow Transplant, ABMT.

Huijgens PC, Ossenkoppele GJ, Simons KA, et al.: Escalating doses of etoposide with dimethylbusulfan as conditioning for autologous bone marrow transplantation. Bone Marrow Transplant 9(3): 218-220, 1992.

Trial Contact Information

Trial Lead Organizations

Vrije Universiteit Medisch Centrum

P. C. Huijgens, MD, PhD, Protocol chair		Ph: 31-20-444-2604 Email: pc.huijgens@vumc.nl