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

Alternate Title

Phenylbutyrate in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed over 18 NCI JHOC-9446 NCI-T94-0196D, T94-0196

Objectives

I.  Evaluate the safety and toxicity of sodium phenylbutyrate (PB) by 7-day 
continuous infusion in patients with myelodysplastic syndrome or relapsed 
acute myeloid leukemia.

II.  Estimate the pharmacokinetics of PB in this patient population and 
escalate the dose, if tolerable, to achieve a target plasma level of 6 mM.

III.  Obtain preliminary clinical and/or laboratory data suggesting potential 
therapeutic activity of PB in these patients.

Entry Criteria

Disease Characteristics:

Myelodysplastic syndrome (MDS) confirmed by bone marrow aspiration or biopsy,
including:
  Primary refractory leukopenia with morphologic features of MDS and AGC less
     than 1,000
  Primary refractory thrombocytopenia with morphologic features of MDS and
     platelets less than 50,000
  Refractory anemia (RA), transfusion dependent
  RA with excess blasts (RAEB)
  RA with ringed sideroblasts (RARS), transfusion dependent
  RAEB in transformation (RAEB-t)
  Chronic myelomonocytic leukemia

Relapsed acute myeloid leukemia (AML) meeting the following criteria:
  WBC less than 30,000 and stable for at least 2 weeks
  Unlikely to require cytotoxic therapy during study
  Ineligible for or declines intensive reinduction therapy with or without
     bone marrow transplantation

Untreated AML
  Patients who refuse chemotherapy for untreated AML or who are deemed
  medically unsuitable candidates for AML induction chemotherapy are eligible
  provided above criteria for AML are met

  Patients with significant curative potential strongly counseled to receive
  curative chemotherapy

No CNS or pulmonary leukostasis

No CNS leukemia

No disseminated intravascular coagulation

Ineligible for or declines higher priority protocols, including:
  For MDS:
     Age under 60 with HLA-matched sibling donor:  allogeneic bone marrow
        transplantation
     Age under 40 with no sibling donor:  consider HLA-matched unrelated donor
  For RAEB-t:  intensive remission induction therapy

Prior/Concurrent Therapy:

At least 3 weeks since hematopoietic growth factors or other treatment and
   recovered
At least 1 month since intensive chemotherapy for MDS

Patient Characteristics:

Age:
  Over 18

Performance status:
  Zubrod 0-2

Life expectancy:
  Not specified

Hematopoietic:
  See Disease Characteristics
  Hemoglobin at least 8 g/dL (transfusion allowed)

Hepatic:
  Bilirubin less than 1.6 mg/dL (unless due to hemolysis)
  AST and ALT less than 2 times normal

Renal:
  Creatinine less than 2 mg/dL

Other:
  No active infection
  No pregnant or nursing women
     Negative serum beta-HCG required
  Adequate contraception required of fertile patients for 2 weeks before,
     during, and for 3 months after treatment

Expected Enrollment

18 patients with MDS will be entered over 12-18 months; 20 patients with 
relapsed AML will be entered over 24 months.  As of 09/95, patients with 
untreated AML who refuse induction chemotherapy or who are medically 
unsuitable for such therapy may be entered.  Such patients are grouped with 
the relapsed AML patients for purposes of dose escalation.

Outline

Single-Agent Chemotherapy.  Phenylbutyrate, PB, NSC-657802.

Gore SD, Weng LJ, Figg WD, et al.: Impact of prolonged infusions of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia. Clin Cancer Res 8 (4): 963-70, 2002.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Steven Gore, MD, Protocol chair		Ph: 410-955-8781 Email: gorest@jhmi.edu