Romidepsin Plus Oral 5-Azacitidine in Relapsed/Refractory Lymphoid Malignancies

NCT ID: NCT01998035

Last Updated: 2024-08-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2020-01-06

Brief Summary

This is an open label, phase I/IIa, 3 x 3 dose escalation study with an initial phase I followed by a disease focused phase II.

The primary objective of the phase I is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of oral 5-azacitidine and romidepsin in patients with lymphoma. The safety and toxicity of this combination will be evaluated throughout the entire study.

If the combination of oral 5-azacitidine and romidepsin is found to be feasible and an MTD is established, the phase II part of the study will be initiated.

Phase II will consist of a 2 stage design of the combination of oral 5-azacitidine and romidepsin for patients with relapsed or refractory T-cell lymphomas.

Detailed Description

Subjects will receive oral 5-azacitidine and romidepsin, administered as follows: oral 5-azacitidine from Days 1-14 (Dose cohorts -1 to 5) or Days 1-21 (Dose cohort 6); and romidepsin administered intravenously on Days 8 (Dose cohorts 1-4) of a 28 day cycle, and Day 22 (Dose cohorts 5 and 6) of a 35 day cycle. Cohorts of 3 patients will be enrolled sequentially as outlined in the dose escalation scheme. Once the MTD is reached the Phase II part of the protocol will be initiated in patients with T-Cell Lymphoma.

Conditions

Lymphoid Malignancies; Lymphoma; Hodgkin Lymphoma; Non-hodgkin Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R/O: Level -1

Oral 5-Azacitidine 100 mg (Days 1-14) Romidepsin (10 mg/m2, Day 8), cycle length (28 days)

Group Type: EXPERIMENTAL

RomiDEPsin 10 MG/M2

Intervention Type: DRUG

Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor".

Dose escalation (10 mg/m2)

Oral 5-Azacitidine 100 MG

Intervention Type: DRUG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity.

Dose escalation (100 mg)

R/O: Level 1

Oral 5-Azacitidine 100 mg (Days 1-14) Romidepsin (10 mg/m2, Days 8 and 15), cycle length (28 days)

Group Type: EXPERIMENTAL

RomiDEPsin 10 MG/M2

Intervention Type: DRUG

Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor".

Dose escalation (10 mg/m2)

Oral 5-Azacitidine 100 MG

Intervention Type: DRUG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity.

Dose escalation (100 mg)

R/O: Level 2

Oral 5-Azacitidine 200 mg (Days 1-14) Romidepsin (10 mg/m2, Days 8 and 15), cycle length (28 days)

Group Type: EXPERIMENTAL

RomiDEPsin 10 MG/M2

Intervention Type: DRUG

Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor".

Dose escalation (10 mg/m2)

Oral 5-Azacitidine 200 MG

Intervention Type: DRUG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity.

Dose escalation (200 mg)

R/O: Level 3

Oral 5-Azacitidine 300 mg (Days 1-14) Romidepsin (10 mg/m2, Days 8 and 15), cycle length (28 days)

Group Type: EXPERIMENTAL

RomiDEPsin 10 MG/M2

Intervention Type: DRUG

Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor".

Dose escalation (10 mg/m2)

Oral 5-Azacitidine 300 MG

Intervention Type: DRUG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity.

Dose escalation (300 mg)

R/O: Level 4

Oral 5-Azacitidine 300 mg (Days 1-14) Romidepsin (14 mg/m2, Days 8 and 15), cycle length (28 days)

Group Type: EXPERIMENTAL

Romidepsin 14 MG/M2

Intervention Type: DRUG

Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor".

Dose escalation (14 mg/m2)

Oral 5-Azacitidine 300 MG

Intervention Type: DRUG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity.

Dose escalation (300 mg)

R/O: Level 5

Oral 5-Azacitidine 300 mg (Days 1-14) Romidepsin (14 mg/m2, Days 8, 15 and 22), cycle length (35 days)

Group Type: EXPERIMENTAL

Romidepsin 14 MG/M2

Intervention Type: DRUG

Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor".

Dose escalation (14 mg/m2)

Oral 5-Azacitidine 300 MG

Intervention Type: DRUG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity.

Dose escalation (300 mg)

R/O: Level 6

Oral 5-Azacitidine 300 mg (Days 1-21) Romidepsin (14 mg/m2, Days 8, 15 and 22), cycle length (35 days)

Group Type: EXPERIMENTAL

Romidepsin 14 MG/M2

Intervention Type: DRUG

Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor".

Dose escalation (14 mg/m2)

Oral 5-Azacitidine 300 MG

Intervention Type: DRUG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity.

Dose escalation (300 mg)

Interventions

RomiDEPsin 10 MG/M2

Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor".

Dose escalation (10 mg/m2)

Intervention Type: DRUG

Oral 5-Azacitidine 100 MG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity.

Dose escalation (100 mg)

Intervention Type: DRUG

Romidepsin 14 MG/M2

Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor".

Dose escalation (14 mg/m2)

Intervention Type: DRUG

Oral 5-Azacitidine 200 MG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity.

Dose escalation (200 mg)

Intervention Type: DRUG

Oral 5-Azacitidine 300 MG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity.

Dose escalation (300 mg)

Intervention Type: DRUG

Other Intervention Names

Istodax; 5-AC; Istodax; 5-AC; 5-AC

Eligibility Criteria

Inclusion Criteria

• Phase I: Histologically confirmed relapsed or refractory non-Hodgkin lymphoma or Hodgkin lymphoma (WHO criteria), with no accepted curative options.
• Phase II: Relapsed or refractory T-cell lymphoma, including patients with central nervous system (CNS) involvement or lymphomatous meningitis are allowed on study.
• Relapsed or refractory disease following frontline chemotherapy. No upper limit for the number of prior therapies. Patients may have relapsed after prior autologous or allogeneic stem cell transplant.
• Evaluable Disease in the Phase I, and measurable disease for the Phase II.
• Age > or = 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status < or = 2.
• Patients must have adequate organ and marrow function.
• Negative urine or serum pregnancy test for females of childbearing potential.
• All females of childbearing potential must use an effective barrier method of contraception during the treatment period and for at least 1 month thereafter. Male subjects should use a barrier method of contraception during the treatment period and for at least 3 months thereafter.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Prior Therapy

• Exposure to chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
• Systemic steroids that have not been stabilized ( ≥ 5 days) to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs.
• No other concurrent investigational agents are allowed.
• History of allergic reactions to Oral 5-azacitidine or Romidepsin.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women.
• Nursing women.
• Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, the patient must be disease-free for ≥ 3 years.
• Patients known to be Human Immunodeficiency Virus (HIV)-positive.
• Patients with active hepatitis A, hepatitis B, or hepatitis C infection.
• Concomitant use of CYP3A4 inhibitors.
• Any known cardiac abnormalities.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Owen A. O'Connor, MD, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center

New York, New York, United States

Countries

United States

References

Falchi L, Ma H, Klein S, Lue JK, Montanari F, Marchi E, Deng C, Kim HA, Rada A, Jacob AT, Kinahan C, Francescone MM, Soderquist CR, Park DC, Bhagat G, Nandakumar R, Menezes D, Scotto L, Sokol L, Shustov AR, O'Connor OA. Combined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: a multicenter phase 2 study. Blood. 2021 Apr 22;137(16):2161-2170. doi: 10.1182/blood.2020009004.

Reference Type: DERIVED

PMID: 33171487 (View on PubMed)

O'Connor OA, Falchi L, Lue JK, Marchi E, Kinahan C, Sawas A, Deng C, Montanari F, Amengual JE, Kim HA, Rada AM, Khan K, Jacob AT, Malanga M, Francescone MM, Nandakumar R, Soderquist CR, Park DC, Bhagat G, Cheng B, Risueno A, Menezes D, Shustov AR, Sokol L, Scotto L. Oral 5-azacytidine and romidepsin exhibit marked activity in patients with PTCL: a multicenter phase 1 study. Blood. 2019 Oct 24;134(17):1395-1405. doi: 10.1182/blood.2019001285.

Reference Type: DERIVED

PMID: 31471376 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AAAM3752

Identifier Type: -

Identifier Source: org_study_id