Phenylbutyrate and Tretinoin in Treating Patients With Hematologic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00006239
First received: September 11, 2000
Last updated: March 9, 2010
Last verified: March 2010
  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
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Investigators
Study Chair: Steven D. Gore, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00006239     History of Changes
Other Study ID Numbers: CDR0000068164, J9879, R01CA067803, P30CA006973, JHOC-J9879, JHOC-99072306, NCI-T98-0068
Study First Received: September 11, 2000
Last Updated: March 9, 2010
Health Authority: United States: Federal Government

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:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
4-phenylbutyric acid
Tretinoin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Keratolytic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on July 28, 2014