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A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275 (NSC 706995, IND 61,198), in Combination With 13-Cis-Retinoic Acid in Metastatic Progressive Cancer.


Phase 1
18 Years
N/A
Not Enrolling
Both
Adult Grade III Lymphomatoid Granulomatosis, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Primary Central Nervous System Non-Hodgkin Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Hodgkin Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Adult T-cell Leukemia/Lymphoma, Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Mycosis Fungoides/Sezary Syndrome, Stage IV Small Lymphocytic Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific, Waldenström Macroglobulinemia

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Trial Information

A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275 (NSC 706995, IND 61,198), in Combination With 13-Cis-Retinoic Acid in Metastatic Progressive Cancer.


PRIMARY OBJECTIVES:

I. Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 when
administered with isotretinoin in patients with metastatic, progressive, refractory, or
unresectable solid tumors or lymphomas.

SECONDARY OBJECTIVES:

I. Determine, preliminarily, tumor response in patients treated with this regimen.

II. Determine the pharmacokinetic profile of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of MS-275.

Patients receive oral MS-275 once on days 1, 8, and 15 and oral isotretinoin twice daily on
days 1-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease
progression. Cohorts of 3-6 patients receive escalating doses of MS-275 until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 12 patients are treated at
the MTD.

Patients are followed monthly.


Inclusion Criteria:



- Histologically confirmed solid tumor or lymphoma

- Metastatic, progressive, refractory, or unresectable disease

- Not amenable to standard curative measures

- No known brain metastases

- Performance status - ECOG 0-2

- More than 3 months

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- WBC ≥ 3,000/mm^3

- Hemoglobin > 9 g/dL

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- No suspected Gilbert's syndrome

- Creatinine ≤ 1.5 times ULN

- Creatinine clearance ≥ 60 mL/min

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No unstable cardiac arryhthmia

- Able to take and retain oral medications

- No malabsorption problems

- No acute or chronic gastrointestinal condition

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double-method contraception 1 month before,
during, and 3 months after study treatment

- No known HIV positivity

- No weight loss > 10% within the past 2 months

- No history of allergic reaction attributed to compounds of similar chemical or
biologic composition to MS-275 or isotretinoin

- No other uncontrolled illness

- No ongoing or active infection

- No seizure disorder

- No psychiatric illness or social situation that would preclude study participation

- More than 4 weeks since prior anticancer vaccine therapy

- More than 4 weeks since prior anticancer immunotherapy

- No concurrent anticancer vaccine therapy

- No concurrent anticancer immunotherapy

- More than 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas,
mitomycin, or other agents known to cause prolonged marrow supression)

- No concurrent anticancer chemotherapy

- More than 4 weeks since prior anticancer hormonal therapy except
gonadotropin-releasing hormone (GnRH) agonist therapy for non-castrated patients with
prostate cancer

- Concurrent GnRH agonist therapy for non-castrated patients with prostate cancer
allowed

- Concurrent luteinizing hormone-releasing hormone agonist therapy allowed provided
there is evidence of tumor progression

- Concurrent adrenal steroid replacement therapy allowed

- No concurrent ketoconazole as second-line hormonal treatment for prostate cancer

- No concurrent corticosteroids except for treatment of refractory nausea or vomiting

- No other concurrent anticancer hormonal therapy

- More than 4 weeks since prior anticancer radiotherapy

- More than 2 weeks since prior palliative radiotherapy

- No concurrent anticancer radiotherapy

- More than 4 weeks since prior major surgery

- Recovered from all prior therapy

- No prior MS-275

- No prior oral isotretinoin

- Isotretinoin for the treatment of acne allowed provided > 3 years since prior
administration

- More than 4 weeks since other prior anticancer therapy

- No concurrent tetracycline

- No concurrent high-dose vitamin A

- No concurrent valproic acid

- No other concurrent investigational agents

- No other concurrent anticancer therapy

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose limiting toxicities defined as an adverse event which is likely related to the study medication

Outcome Description:

Graded using the CTCAE version 3.0.

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Roberto Pili

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02634

NCT ID:

NCT00098891

Start Date:

October 2004

Completion Date:

Related Keywords:

  • Adult Grade III Lymphomatoid Granulomatosis
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Intraocular Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Primary Central Nervous System Non-Hodgkin Lymphoma
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Adult T-cell Leukemia/Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Stage IV Adult Burkitt Lymphoma
  • Stage IV Adult Diffuse Large Cell Lymphoma
  • Stage IV Adult Diffuse Mixed Cell Lymphoma
  • Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage IV Adult Hodgkin Lymphoma
  • Stage IV Adult Immunoblastic Large Cell Lymphoma
  • Stage IV Adult Lymphoblastic Lymphoma
  • Stage IV Adult T-cell Leukemia/Lymphoma
  • Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage IV Grade 1 Follicular Lymphoma
  • Stage IV Grade 2 Follicular Lymphoma
  • Stage IV Grade 3 Follicular Lymphoma
  • Stage IV Mantle Cell Lymphoma
  • Stage IV Marginal Zone Lymphoma
  • Stage IV Mycosis Fungoides/Sezary Syndrome
  • Stage IV Small Lymphocytic Lymphoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Waldenström Macroglobulinemia
  • Burkitt Lymphoma
  • Hodgkin Disease
  • Immunoblastic Lymphadenopathy
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Waldenstrom Macroglobulinemia
  • Mycoses
  • Mycosis Fungoides
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Lymphoma, Mantle-Cell

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205