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

NCT01998035 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: AAAM3752
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Lymphoid Malignancies; Lymphoma; Hodgkin Lymphoma; Non-hodgkin Lymphoma; Follicular Lymphoma; Diffuse Large B-Cell Lymphoma; Anaplastic Large Cell Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Burkitt Lymphoma; Waldenstrom Macroglobulinemia; Peripheral T-cell Lymphoma; Cutaneous T-cell Lymphoma

Outcome Measures

Primary Outcomes (4)

• Phase I: Maximum Tolerated Dose (MTD) of the Combination of Oral 5-azacitidine in Combination With Romidepsin

  The highest dose of a drug or treatment that does not cause unacceptable side effects. The MTD is determined in clinical trials by testing increasing doses on different groups of people until the highest dose with acceptable side effects is found.

  up to 1.5 years

• Phase I: Maximum Tolerated Dose (MTD) of Romidepsin in Combination With Oral 5-azacytidine

  The highest dose of a drug or treatment that does not cause unacceptable side effects. The MTD is determined in clinical trials by testing increasing doses on different groups of people until the highest dose with acceptable side effects is found.

  up to 1.5 years

• Percentage of Patients Who Experienced Significant Toxicities in Phase 1

  Patients receiving the combination of oral 5-azacitidine and romidepsin and experiencing grades 1-4 toxicities will be tallied based on events observed and assessed by a qualified investigator. This Outcome Measure is specifically for Phase 1 of the study.

  Up to 1.5 years

• Phase II: Overall Response Rate (ORR) (Complete + Partial Response) of the Combination of Oral 5-azacitidine and Romidepsin in Patients With Relapsed/Refractory T-Cell Lymphoma

  The percentage of people in a study or treatment group who have a partial response or complete response to the treatment within a certain period of time. A partial response is a decrease in the size of a tumor or in the amount of cancer in the body, and a complete response is the disappearance of all signs of cancer in the body. In a clinical trial, measuring the ORR is one way to see how well a new treatment works.

  Up to 3 years

Study Arms (7)

R/O: Level -1

EXPERIMENTAL

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

Drug: RomiDEPsin 10 MG/M2; Drug: Oral 5-Azacitidine 100 MG

R/O: Level 1

EXPERIMENTAL

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

Drug: RomiDEPsin 10 MG/M2; Drug: Oral 5-Azacitidine 100 MG

R/O: Level 2

EXPERIMENTAL

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

Drug: RomiDEPsin 10 MG/M2; Drug: Oral 5-Azacitidine 200 MG

R/O: Level 3

EXPERIMENTAL

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

Drug: RomiDEPsin 10 MG/M2; Drug: Oral 5-Azacitidine 300 MG

R/O: Level 4

EXPERIMENTAL

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

Drug: Romidepsin 14 MG/M2; Drug: Oral 5-Azacitidine 300 MG

R/O: Level 5

EXPERIMENTAL

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

Drug: Romidepsin 14 MG/M2; Drug: Oral 5-Azacitidine 300 MG

R/O: Level 6

EXPERIMENTAL

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

Drug: Romidepsin 14 MG/M2; Drug: Oral 5-Azacitidine 300 MG

Interventions

RomiDEPsin 10 MG/M2 DRUG

Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor". Dose escalation (10 mg/m2)

Also known as: Istodax

R/O: Level -1; R/O: Level 1; R/O: Level 2; R/O: Level 3

Oral 5-Azacitidine 100 MG DRUG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity. Dose escalation (100 mg)

Also known as: 5-AC

R/O: Level -1; R/O: Level 1

Romidepsin 14 MG/M2 DRUG

Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor". Dose escalation (14 mg/m2)

Also known as: Istodax

R/O: Level 4; R/O: Level 5; R/O: Level 6

Oral 5-Azacitidine 200 MG DRUG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity. Dose escalation (200 mg)

Also known as: 5-AC

R/O: Level 2

Oral 5-Azacitidine 300 MG DRUG

A pyrimidine nucleoside analogue of cytidine with antineoplastic activity. Dose escalation (300 mg)

Also known as: 5-AC

R/O: Level 3; R/O: Level 4; R/O: Level 5; R/O: Level 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead
• Celgene: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10019, United States

Location

Related Publications (2)

• 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.

  PMID: 33171487 DERIVED

• 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.

  PMID: 31471376 DERIVED

MeSH Terms

Conditions

Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Anaplastic; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Burkitt Lymphoma; Waldenstrom Macroglobulinemia; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous

Interventions

romidepsin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, T-Cell; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Results Point of Contact

• Title: Ana Ignat
• Organization: Columbia University Irving Medical Center

ai2111@cumc.columbia.edu

212-305-3612

Study Officials

• Owen A. O'Connor, MD, Ph.D.

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2013
• First Posted: November 28, 2013
• Study Start: November 1, 2013
• Primary Completion: January 6, 2020
• Study Completion: January 6, 2020
• Last Updated: August 22, 2024
• Results First Posted: August 22, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)