Clinical trial NCT00004058: 12-O-Tetradecanoylphorbol-13-acetate in Treating Patients With Hematologic Cancer or Bone Marrow Disorder
Official title: Phase I Study of 12-O-tetradecanoylphorbol-13-acetate (TPA) in Patients With Refractory Hematologic Malignancies/Bone Marrow Disorders
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Precancerous/Nonmalignant Condition
Keywords: monoclonal gammopathy of undetermined significance
recurrent adult Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
isolated plasmacytoma of bone
extramedullary plasmacytoma
refractory multiple myeloma
Waldenstrom macroglobulinemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
polycythemia vera
chronic idiopathic myelofibrosis
essential thrombocythemia
refractory hairy cell leukemia
refractory anemia
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
T-cell large granular lymphocyte leukemia
acute undifferentiated leukemia
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
recurrent adult T-cell leukemia/lymphoma
secondary acute myeloid leukemia
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
primary central nervous system lymphoma
prolymphocytic leukemia
primary systemic amyloidosis
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
refractory cytopenia with multilineage dysplasia
recurrent mycosis fungoides/Sezary syndrome
chronic eosinophilic leukemia
chronic neutrophilic leukemia
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Roger Strair, MD, PhD
role: STUDY_CHAIR
References: