12-O-Tetradecanoylphorbol-13-acetate in Treating Patients With Hematologic Cancer or Bone Marrow Disorder

University of Medicine and Dentistry of New Jersey

Status and phase: Terminated; Phase 1

Conditions: Multiple Myeloma and Plasma Cell Neoplasm; Chronic Myeloproliferative Disorders; Precancerous/Nonmalignant Condition; Lymphoma; Leukemia; Myelodysplastic/Myeloproliferative Diseases; Myelodysplastic Syndromes

Treatments: Drug: tetradecanoylphorbol acetate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00004058

CINJ-059806

P30CA072720 (U.S. NIH Grant/Contract)

5986 CDR0000067255;

NCI-G99-1573

UMDNJ-2716

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of 12-O-tetradecanoylphorbol-13-acetate in treating patients with hematologic cancer or bone marrow disorder that has not responded to previous treatment.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose and dose limiting toxicity of 12-O-tetradecanoylphorbol-13-acetate (TPA) in patients with relapsed or refractory hematologic malignancies or bone marrow disorders.
• Determine the pharmacokinetics of TPA in these patients.
• Determine the effects of TPA on the cellular composition of blood and bone marrow in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive 12-O-tetradecanoylphorbol-13-acetate (TPA) IV over 1 hour on days 1 and 8 followed by 2 weeks of rest. Courses repeat in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of TPA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose limiting toxicity.

PROJECTED ACCRUAL: Approximately 36 patients will be accrued for this study.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically proven relapsed or refractory hematologic malignancy or bone marrow disorder for which there is no standard curative therapy, including, but not limited to:

  • Myelodysplasia
  • Multiple myeloma
  • Myeloproliferative syndrome
  • Chronic lymphocytic leukemia
  • Aplastic anemia
  • Non-Hodgkin's lymphoma
  • Acute leukemia
  • Hodgkin's lymphoma
  • Chronic myelogenous leukemia

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• ECOG 0-2

Life expectancy:

• Greater than 1 month

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 3 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• Cardiac ejection fraction greater than 40%

Pulmonary:

• FEV_1 greater than 50% predicted

Other:

• No active infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 10 weeks after study participation
• No uncontrolled psychiatric or medical illness

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Greater than 3 weeks since prior biologic therapy

Chemotherapy:

• Greater than 3 weeks since prior chemotherapy and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No other concurrent investigational agents