An Open Label, International, Multi-centre, Phase I/IIa Study of Lenalidomide (Revlimid) and Romidepsin (Istodax) for Relapsed /Refractory Hodgkin Lymphoma, Mature T-cell Lymphoma and Multiple Myeloma. (RId Study)

NCT01742793 | Terminated Phase 1 DMC

• 2 other identifiers: 1112009392115541
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The study hypothesis is that lenalidomide and romidepsin (and dexamethasone for patients with myeloma) will have an acceptable toxicity profile and that in combination will have sufficient activity in the target population (including those previously refractory to HDACi monotherapy) to warrant further investigation.

Conditions

Hodgkin's Lymphoma; Mature T-cell Lymphoma; Multiple Myeloma

Keywords

relapsed /refractory Hodgkin lymphoma; mature T-cell lymphoma; multiple myeloma

Outcome Measures

Primary Outcomes (2)

• Overall Rate of Clinical Response (Complete Response + Partial Response)

  Overall response rate is a combination of partial response and complete response according to specific response criteria that will be used throughout the study.

  12 months

• Overall Rate of Clinical Response (Complete Response + Partial Response)

  Overall response rate is a combination of partial response and complete response according to specific response criteria that will be used throughout the study.

  24 months

Secondary Outcomes (1)

• Rate of Overall survival (OS)

  From date of randomization until the date of death from any cause, assessed up to 70 months.

Study Arms (2)

Arm L: subjects with lymphoma

EXPERIMENTAL

The following dosing steps will be applied to the dose-escalation, phase-I component of the study for patients with lymphoma who are eligible to enter Arm L: Dose Level Arm L Lenalidomide dose Oral Romidepsin Dose Intravenous * 2 10mg D1-7, D15-21 6mg D1, 8, 15 * 1 10mg D1-7, D15-21 8mg D1, 8, 15 1. 10mg D1-21 8mg D1, 8, 15 2 15mg D1-21 8mg D1, 8, 15 3 15mg D1-21 10mg D1, 8, 15 4 15mg D1-21 12mg D1, 8, 15 5 15mg D1-21 14mg D1, 8, 15 6 25mg D1-21 14mg D1, 8, 15 * The first patient in arm L will be entered into the study at dosing level one.

Drug: lenalidomide (Revlimid) and romidepsin (Istodax)

Arm M: subjects with myeloma

EXPERIMENTAL

The following dosing steps will be applied to the dose-escalation, phase-I component of the study for patients with myeloma who are eligible to enter Arm M: Dose Level Arm M Lenalidomide dose Oral Romidepsin Dose Intravenous Dexamethasone * 2 15mg D1-7, D15-21 6mg D1, 8, 15 20mg D1,8,15,22 * 1 15mg D1-7, D15-21 8mg D1, D8, 15 20mg D1,8,15,22 1. 15mg D1-21 8mg D1, 8, 15 20mg D1,8,15,22 2 25mg D1-21 8mg D1, 8, 15 20mg D1,8,15,22 3 25mg D1-21 10mg D1, 8, 15 20mg D1,8,15,22 4 25mg D1-21 12mg D1, 8, 15 20mg D1,8,15,22 5 25mg D1-21 14mg D1, 8, 15 20mg D1,8,15,22 * The first patient in arm M will be entered into the study at dosing level one.

Drug: lenalidomide (Revlimid) and romidepsin (Istodax)

Interventions

lenalidomide (Revlimid) and romidepsin (Istodax) DRUG

Arm L: subjects with lymphoma; Arm M: subjects with myeloma

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Mature T-Cell lymphoma. The following entities are eligible. PTCL or CTCL (including MF and SS) but excluding adult T-cell leukemia/lymphoma, primary cutaneous CD30+ lymphoma, lymphomatoid papulosis, and NK or LGL leukemia.(The complete WHO classification of T-cell lymphoma can be found in the appendices).
• Peripheral T-cell lymphoma: patients must have relapsed or progressed after: at least one prior chemotherapy-based treatment, or not suitable for a conventional chemotherapeutic approach as judged by the investigator.
• Sezary syndrome/ Mycosis Fungoides: patients must have relapsed or progressed after at least one prior systemic therapy.
• B. Hodgkin lymphoma
• At least one prior chemotherapy-based treatment.
• Prior autograft in those eligible for autologous transplantation according to institutional guidelines.
• C. Myeloma
• Relapsed after at least one prior systemic therapy that includes thalidomide (unless intolerant or contraindicated) or lenalidomide. Those who have received prior lenalidomide must have had a response that exceeded 6 months.
• Patients who are candidates for autologous stem cell transplant in first remission are not eligible.
• Patients must have failed/relapsed after bortezomib therapy.
• ECOG performance status \<2
• Age \>18 years.
• Life expectancy ≥90 days.
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count \>1.0 x109/L (or greater than 0.75x109/L if \>50% plasma cells or \>50% lymphoma in the bone marrow) Neutrophil count must not be supported by G-CSF prior to study entry. platelets \>100 x109/L (or \>75 x 109 if \>50% plasma cells or \>50% lymphoma in the bone marrow).

You may not qualify if:

• Patients receiving any other investigational agents within 4 weeks.
• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not adequately recovered from grade III/IV adverse events due to agents administered more than 4 weeks earlier.
• Prior exposure to lenalidomide, in patients with myeloma, except if a response (including stable disease) was maintained for at least 6 months. (Washout period of 4 weeks required)
• Prior treatment with HDAC inhibitor (not including sodium valproate for neurological or psychiatric disorders), except if response (including stable disease) was maintained for at least 3 months. (Washout period of 4 weeks required)
• Concomitant treatment with sodium valproate (washout 4 weeks required).
• Central nervous system involvement by lymphoma or myeloma.
• A history of allergic reaction to romidepsin or lenalidomide, boron or mannitol.
• A history of Gr III/IV drug-related non-hematological toxicity, excluding thromboembolism or sepsis, in a prior exposure to either lenalidomide or a histone deacetylase inhibitor.
• Concomitant corticosteroid except for patients on a stable dose of ≤10mg prednisone/day for at least 4 weeks prior to screening.
• Congenital long QT syndrome, or a QTc interval \>450 milliseconds
• Patients who have had a myocardial infarction within twelve months of study entry.
• Patients who have active coronary artery disease (for example NYHA class II or above angina).
• Any patient in whom coronary artery disease is suspected should be referred for a cardiology consultation and if active myocardial ischemia is demonstrated, the patient should be excluded. If a non-invasive imaging study is equivocal, it may be necessary to proceed to coronary angiography.
• Patients with a baseline ECG showing evidence of cardiac ischaemia (ST depression of ≥2mm)
• Patients with NYHA-class congestive heart failure ≥II

Sponsors & Collaborators

• Yale University: lead
• Peter MacCallum Cancer Centre, Australia: collaborator

Study Sites (1)

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

Related Links

• Yale Cancer Center Website

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, T-Cell; Multiple Myeloma

Interventions

Lenalidomide; romidepsin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Francine Foss, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 21, 2012
• First Posted: December 5, 2012
• Study Start: October 1, 2012
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: March 4, 2020

Record last verified: 2017-02

Locations

US (1)