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Phase I Study of Bryostatin 1 (NSC 339555) and High-Dose 1-Beta-D-Arabinofuranosylcytosine (HiDAC) in Patients With Refractory Leukemia


Phase 1
18 Years
N/A
Not Enrolling
Both
Leukemia, Lymphoma

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Trial Information

Phase I Study of Bryostatin 1 (NSC 339555) and High-Dose 1-Beta-D-Arabinofuranosylcytosine (HiDAC) in Patients With Refractory Leukemia


OBJECTIVES: I. Define the maximum tolerated dose (MTD) of bryostatin 1 administered before
and after high dose cytarabine in patients with refractory or relapsed acute myelocytic
leukemia or acute lymphocytic leukemia, chronic myelogenous leukemia, or refractory or
relapsed lymphoblastic lymphoma. II. Describe the toxic effects of bryostatin 1 and high
dose cytarabine in these patients. III. Describe the time course of bryostatin 1 induced
modulation of leukemic blast total protein kinase C (PKC) activity. IV. Describe bryostatin
1 pharmacokinetics. V. Correlate bryostatin 1 induced modulation of leukemic cell PKC
activity or leukemic cell maturation with high dose cytarabine mediated apoptosis.

OUTLINE: This is a dose escalation study. Patients receive bryostatin 1 by continuous
infusion over 24 hours on day 1. One hour after completion of bryostatin 1, patients receive
high dose cytarabine IV over 3 hours every 12 hours on days 2-4. Patients again receive
cytarabine over 3 hours every 12 hours on days 9-11, followed 1 hour later by bryostatin 1
by continuous infusion over 24 hours beginning on day 11. Patients achieving complete
remission may receive up to 4 courses of consolidation chemotherapy. Consolidation
chemotherapy is the same as induction chemotherapy except patients receive only 2 doses of
cytarabine after day 1 completion of bryostatin and only 2 doses of cytarabine prior to the
day 11 dose of bryostatin. Patients achieving partial remission may receive a second course
of induction chemotherapy. In the absence of dose limiting toxicity in the first 3 patients
treated, subsequent cohorts of 6 patients receive escalating doses of bryostatin 1 on the
same schedule. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level,
then dose escalation ceases and the current dose is defined as the maximum tolerated dose.
Patients are followed every 6 months until death.

PROJECTED ACCRUAL: A total of 12-50 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically confirmed primary refractory or relapsed acute
myelocytic leukemia (AML) or acute lymphocytic leukemia (ALL), chronic myelogenous
leukemia (CML) in blast crisis, or refractory or relapsed lymphoblastic lymphoma Priority
is given to patients previously treated with conventional high dose cytarabine regimen
without bryostatin 1 Eligible if previously failed a conventional high dose cytarabine
regimen or if underwent subsequent high dose therapy with bone marrow/stem cell
transplantation with curative intent

PATIENT CHARACTERISTICS: Age: 18 and over (must be 60 or under if receiving higher dose of
cytarabine) Performance status: Karnofsky 60-100% Life expectancy: Not specified
Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL (bilirubin no
greater than 3.0 mg/dL and conjugated bilirubin no greater than 0.5 mg/dL if Gilbert's
disease and predominantly unconjugated hyperbilirubinemia present) AST no greater than 2.5
times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN
Renal: Creatinine clearance at least 40 mL/min (at least 60 mL/min if receiving higher
dose of cytarabine) Pulmonary: No clinically significant pulmonary disease Other: Not
pregnant No patients who are poor medical risks because of nonmalignant systemic disease
No serious, active, uncontrolled infection No prior or concurrent medical status that
would make assessing cortical or cerebellar neurologic toxicity difficult

PRIOR CONCURRENT THERAPY: Recovery from the major toxic effects of prior therapy required
Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics At
least 24 hours since prior chemotherapy with hydroxyurea At least 3 weeks since other
prior systemic chemotherapy No prior clinically significant cerebellar toxicity due to
cytarabine Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not
specified

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Steven Grant, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Massey Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000065773

NCT ID:

NCT00003079

Start Date:

September 1997

Completion Date:

May 2001

Related Keywords:

  • Leukemia
  • Lymphoma
  • recurrent adult acute myeloid leukemia
  • recurrent adult acute lymphoblastic leukemia
  • blastic phase chronic myelogenous leukemia
  • recurrent adult lymphoblastic lymphoma
  • Leukemia
  • Lymphoma

Name

Location
University of Texas - MD Anderson Cancer Center Houston, Texas  77030-4009
New York Presbyterian Hospital - Cornell Campus New York, New York  10021
Massey Cancer Center Richmond, Virginia  23298-0037