Phase II Study of TPA Plus Dexamethasone & CMT in Hematologic Malignancies

NCT01009931 | Terminated Phase 2 Results

• 5 other identifiers: 020702P30CA0684850220080085P30CA072720NCI-2011-03242
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial is studying the side effects and how well giving tetradecanoylphorbol acetate together with dexamethasone and choline magnesium trisalicylate works in treating patients with relapsed or refractory acute myeloid leukemia.

Conditions

Leukemia

Keywords

Acute Myelogenous Leukemia; Relapsed AML; Refractory AML

Outcome Measures

Primary Outcomes (2)

• Response Rate > 20% for 12-O-tetradecanoylphorbol-13- Acetate (TPA)+ Dexamethasone + Choline Magnesium Trisalicylate(Trilisate)

  42 months

• Grade 3 and 4 Non-hematologic Treatment-related Toxicity Rates < 25%

  43 months

Secondary Outcomes (1)

• Effects of Treatment on Immunophenotype, Signaling Profile, and Nuclear NF-kB Expression

  48 months

Study Arms (1)

TPA + Dexamethasone and CMT

EXPERIMENTAL

12-O-tetradecanoylphorbol-13-acetate (TPA) plus Dexamethasone \& Choline magnesium trisalicylate (Trilisate)

Drug: 12-O-tetradecanoylphorbol-13-acetate; Drug: Dexamethasone; Drug: Choline magnesium trisalicylate

Interventions

12-O-tetradecanoylphorbol-13-acetate DRUG

The initial dose of TPA will be 1 mg/week x 3 weeks (Day 1, 8, 15). Up to 6 cycles.

Also known as: TPA

TPA + Dexamethasone and CMT

Dexamethasone DRUG

Dexamethasone 10 mg PO qid will start 24h prior to TPA and continue for 24h after TPA x 3 weeks. Up to 6 cycles.

Also known as: Dexamethasone sodium phosphate

TPA + Dexamethasone and CMT

Choline magnesium trisalicylate DRUG

Choline magnesium trisalicylate 1500 mg PO TID will begin 24h prior to TPA and continue for 24h post TPA x 3 weeks. Up to 6 cycles.

Also known as: Trilisate

TPA + Dexamethasone and CMT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have a histologically documented relapsed/refractory AML for which there is no standard therapy that has been demonstrated to have curative or palliative potential.
• ECOG performance status of 0-2.
• Must be 18 years or older.
• Estimated life expectancy \> 1 month.
• Laboratory data:
• total bilirubin ≤ 1.5 x upper limit of normal unless due to Gilbert's syndrome
• serum creatinine ≤ 2.0 mg/dl
• AST ≤ 3.0 x upper limit of normal
• Cardiac ejection fraction \> 40%
• FEV1.0 \> 50% predicted
• Prior therapy: \> 3 weeks since chemotherapy, biological therapy or radiation; anticipated maximum hematological improvement since last dose of chemotherapy. (Concurrent hydroxyurea administration will be allowed to control WBC count, platelet count, or symptoms).
• No active infections.
• Negative pregnancy test for women of childbearing potential.
• No uncontrolled psychiatric illness or medical illness that the principal investigator feels will compromise the patient's tolerance of the study medication.
• Must provide informed consent.

You may not qualify if:

• Patients with an allergy to proton pump inhibitors, required for GI prophylaxis; or salicylates are excluded.
• Pregnant or lactating women
• Age \<18 years. Because no dosing or adverse event data are currently available on the use of TPA alone or in combination with dexamethasone in patients \< 18 years of age, children are excluded from this study but will be eligible for future pediatric Phase II combination trials.
• The effects of TPA on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 10 weeks after. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Should the female partner of a participant in this study become pregnant or suspect she is pregnant during this study, the PI of this study will be available to provide advice about further medical/obstetric care/referral for the female partner.
• Patients with active CNS involvement (documented by radiographic lesions and/or malignant cells in the CSF) will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Patients with treatment of any other investigational drug within the last 30 days prior to entering the study.

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• Rutgers Cancer Institute of New Jersey: collaborator
• National Cancer Institute (NCI): collaborator
• Biosuccess Biotech Co., Ltd.: collaborator

Study Sites (1)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute

Interventions

Tetradecanoylphorbol Acetate; Dexamethasone; dexamethasone 21-phosphate; choline magnesium trisalicylate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Phorbol Esters; Phorbols; Diterpenes; Terpenes; Hydrocarbons; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Tatiana Zelinskaya
• Organization: Rutgers Cancer Institute of New Jersey

zelinsta@cinj.rutgers.edu

(732) 235-9837

Study Officials

• Roger Strair, MD, PhD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2009
• First Posted: November 9, 2009
• Study Start: March 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: September 1, 2014
• Last Updated: November 4, 2015
• Results First Posted: June 22, 2015

Record last verified: 2015-11

Locations

US (1)