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Phenylbutyrate and Tretinoin in Treating Patients With Hematologic Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00006239
First Posted: January 27, 2003
Last Update Posted: September 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Tretinoin may help hematologic cancer cells develop into normal white blood cells.

PURPOSE: Phase I trial to study the effectiveness of combining phenylbutyrate and tretinoin in treating patients who have hematologic cancer.


Condition Intervention Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Drug: sodium phenylbutyrate Drug: tretinoin Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I, Dose-Finding Trial of Sodium Phenylbutrate (NSC 657802) in Combination With All Trans-retinoic Acid (ATRA, NSC 122758) in Patients With Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Study Start Date: December 2000
Study Completion Date: March 2005
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the safety and toxicity of phenylbutyrate and tretinoin in patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.
  • Determine the pharmacokinetic interaction of this regimen in these patients.
  • Determine any potential therapeutic activity of this regimen in these patients.

OUTLINE: This is a dose escalation study of tretinoin.

Patients receive phenylbutyrate IV continuously on days 1-7 of weeks 1, 5, 7, 9, 11, 13, 15, 17, and 19. Patients also receive oral tretinoin three times daily on days 1-7 of weeks 3, 5, 7, 9, 11, 13, 15, 17, and 19. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tretinoin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose limiting toxicities.

An additional cohort of 6 patients is accrued at the MTD. These patients receive phenylbutyrate IV continuously on days 1-3 of weeks 1 and 3-18. These patients also receive oral tretinoin three times daily on days 1-3 of weeks 2-18. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 18 months.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed myelodysplastic syndrome (MDS)

    • Refractory anemia
    • Primary refractory leukopenia or thrombocytopenia with morphologic features of MDS
    • Refractory anemia with excess blasts (RAEB)
    • Refractory anemia with ringed sideroblasts
    • RAEB in transformation
    • Must have excess blasts or be hematopoietically compromised, defined as one of the following:

      • RBC transfusion dependent
      • Granulocyte count less than 1,000/mm^3
      • Platelet count less than 50,000/mm^3 OR
  • Diagnosis of chronic myelomonocytic leukemia

    • Hematopoietically compromised (as defined above) OR
    • Excess blasts OR
    • Evaluable disease related symptomatology (organomegaly or leukemia cutis) OR
  • Diagnosis of acute myeloid leukemia

    • WBC less than 20,000/mm^3 and stable for at least 2 weeks
    • Unlikely to require cytotoxic therapy during study
  • No CNS or pulmonary leukostasis or CNS leukemia

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Zubrod 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics
  • Hemoglobin at least 8 g/dL (transfusion allowed)
  • No disseminated intravascular coagulation

Hepatic:

  • Bilirubin less than 2.0 mg/dL (unless due to hemolysis or Gilbert's syndrome)

Renal:

  • Creatinine less than 2.0 mg/dL

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for 2 weeks prior, during, and for 3 months after study
  • No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics
  • At least 3 weeks since prior biologic therapy, including hematopoietic growth factors, and recovered

Chemotherapy:

  • See Disease Characteristics
  • At least 3 weeks (1 month for MDS patients) since prior chemotherapy and recovered

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 3 weeks since prior radiotherapy and recovered

Surgery:

  • Not specified
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006239


Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Study Chair: Steven D. Gore, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00006239     History of Changes
Other Study ID Numbers: J9879 CDR0000068164
R01CA067803 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
JHOC-J9879
JHOC-99072306
NCI-T98-0068
First Submitted: September 11, 2000
First Posted: January 27, 2003
Last Update Posted: September 29, 2017
Last Verified: September 2017

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
refractory anemia
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
previously treated myelodysplastic syndromes
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)

Additional relevant MeSH terms:
Syndrome
Leukemia
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
4-phenylbutyric acid
Tretinoin
Antineoplastic Agents
Keratolytic Agents
Dermatologic Agents