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A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma


Phase 1
18 Years
N/A
Not Enrolling
Both
Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Mantle Cell Lymphoma

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Trial Information

A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma


PRIMARY OBJECTIVES:

I. Determine the minimally effective pharmacological dose (MEPD) of single-agent decitabine
in patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma.

II. Determine the maximum tolerated dose of valproic acid when administered with the MEPD of
decitabine in these patients.

III. Determine the MEPD of valproic acid when administered with decitabine in these
patients.

IV. Determine the toxic effects of decitabine alone and in combination with valproic acid in
these patients.

SECONDARY OBJECTIVES:

I. Determine the response rate in patients treated with these drugs. II. Determine the
pharmacokinetics of these drugs in these patients.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 treatment stages.

STAGE 1: Patients receive decitabine IV over 1 hour on days 1-5 or 1-10. Treatment repeats
every 28 days for up to 12 courses in the absence of disease progression or unacceptable
toxicity.

STAGE 2: Patients receive decitabine as in stage 1 and valproic acid orally (PO) thrice
daily (TID) on days 5-21. Treatment repeats every 28 days for up to 12 courses in the
absence of disease progression or unacceptable toxicity.

For both stages, patients who achieve an objective response (complete response [CR],
unconfirmed CR, or partial response) may discontinue study treatment and undergo stem cell
transplantation, if eligible.

PROJECTED ACCRUAL: Approximately 18-42 patients (18 for stage 1 and 24 for stage 2) will be
accrued for this study.


Inclusion Criteria:



- Histologically or cytologically confirmed aggressive B-cell non-Hodgkin's lymphoma
(NHL), including any of the following subtypes:

- Mantle cell lymphoma

- Diffuse large cell lymphoma

- Burkitt's lymphoma

- Transformed NHL* arising from a previously diagnosed low-grade lymphoma,
including any of the following:

- Follicular lymphoma

- Small lymphocytic lymphoma

- Chronic lymphocytic leukemia

- Relapsed or refractory disease

- Relapsed or refractory disease must have occurred during the most recent prior
therapy

- Has accessible tissue for biopsy OR evidence of ≥ 50% bone marrow involvement AND
willing to undergo serial biopsy

- Not eligible for OR refused curative stem cell transplantation

- No active or untreated CNS lymphoma

- Performance status - ECOG 0-2

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

- Platelet count ≥ 75,000/mm^3

- AST and ALT ≤ 2.5 times upper limit of normal

- Bilirubin ≤ 1.5 mg/dL

- Creatinine ≤ 2.0 mg/dL

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No known HIV positivity

- No ongoing or active infection

- No other uncontrolled illness

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

- Prior stem cell transplantation allowed

- Recovered from all prior biologic therapy-related toxicity

- Recovered from all prior chemotherapy-related toxicity

- No other concurrent chemotherapy unless it is used in the chronic daily setting for
other medical conditions, including pulmonary, rheumatologic, or adrenal disorders

- No concurrent corticosteroids unless they are used in the chronic daily setting for
other medical conditions, including pulmonary, rheumatologic, or adrenal disorders

- Recovered from all prior radiotherapy-related toxicity

- No concurrent palliative radiotherapy

- Recovered from all prior therapy-related toxicity

- No concurrent anticonvulsants, including valproic acid (except as used in this study)

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MEPD of single agent decitabine defined as the dose where an 80% decrease in DNMT1 protein level and a 100% increase in re-expression of the methylated target genes are noted in 5 of 6 patients, with DLT in less than or equal to 1 patient

Outcome Time Frame:

28 days

Safety Issue:

No

Principal Investigator

Kristie Blum

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01465

NCT ID:

NCT00109824

Start Date:

March 2006

Completion Date:

Related Keywords:

  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Burkitt Lymphoma
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Mantle-Cell

Name

Location

Ohio State University Medical CenterColumbus, Ohio  43210