Combination Therapy With Carfilzomib, Romidepsin, Lenalidomide in Patients With Relapsed or Refractory B- and T-cell Lymphomas

NCT02341014 | Completed Phase 1 Results

• 1 other identifier: 14-179
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open label phase Ib/IIa study of patients with relapsed/refractory B- and T-cell lymphomas who are treated with carfilzomib, lenalidomide and romidepsin.

Conditions

T-cell Lymphomas; Relapsed or Refractory

Keywords

Carfilzomib; Romidepsin; Lenalidomide; Lymphomas; 14-179

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose of Romidepsin

  Determine the MTD by NCI-CTCAE v4.0.

  21 days

• Maximum Tolerated Dose of Lenalidomide

  Determine the MTD by NCI-CTCAE v4.0.

  21 days

• Maximum Tolerated Dose of Carfilzomib

  Determine the MTD by NCI-CTCAE v4.0.

  21 days

Secondary Outcomes (1)

• Overall Response Rate (Orr) at the Maximum Tolerated Dose

  1 year

Study Arms (1)

Carfilzomib, Romidepsin, Lenalidomide

EXPERIMENTAL

All patients will be treated with romidepsin administered intravenously on days 1 and 8 of a 21-day cycle. Lenalidomide will be taken orally daily for days 1-14 of a 21-day cycle. The carfilzomib will be given weekly on days 1, and 8 of a 21-day cycle.

Drug: Carfilzomib; Drug: Romidepsin; Drug: Lenalidomide

Interventions

Carfilzomib DRUG

The initial dose of carfilzomib (cycle 1, day 1) given to any patient must be 20mg/m2 .

Carfilzomib, Romidepsin, Lenalidomide

Romidepsin DRUG

Carfilzomib, Romidepsin, Lenalidomide

Lenalidomide DRUG

Carfilzomib, Romidepsin, Lenalidomide

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed B- or T-cell lymphomas at the enrolling institution, including stage ≥ Ib CTCL, which has relapsed or progressed after at least one systemic therapy.
• Hodgkin lymphoma is allowed and will be classified as a B-cell lymphoma in the phase IIA portion.
• Age ≥ 18,
• Previous systemic anti-cancer therapy must have been discontinued at least 3 weeks prior to treatment and adverse effects must have resolved to ≤Grade 1 or baseline. In the phase IIa portion, in progressing subjects, a 2 week washout may be allowed after discussion with the MSK Principal Investigator.
• ECOG ≤ 2
• Meet the following laboratory criteria:
• Absolute neutrophil count 1.0/mm³,
• Platelet count 80 K/μ (in the Phase II portion, if thrombocytopenia is due to bone marrow involvement platelet count must be 50 K/μL),
• Phase Ib subjects must have calculated creatinine clearance 50ml/min by Cockcroft-Gault formula, phase IIa subjects must have calculated creatinine clearance ≥ 40ml4/min by Cockcroft-Gault formula.
• Total bilirubin 1.5 x upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) 3 x ULN
• Measurable disease for phase IIa portion only.
• Lymphoma (includes CTCL patients who are without evidence of the disease in the skin): CT or PET/CT by modified Cheson criteria with incorporation of PET.
• CTCL: mSWAT \>0, or absolute Sezary count ≥ 1000 cells/μL.
• All study participants must be registered into the mandatory Revlimid REMS ® program, and be willing and able to comply with the requirements of the REMS ® program.
• Short course systemic corticosteroids for disease control, improvement of performance status or non-cancer indication (\< 7 days) must have been discontinued at least 6 days prior to study treatment. Stable ongoing corticosteroid use (≥ 30 days) up to an equivalent dose of 15 mg of prednisone is permissible.

You may not qualify if:

• Patients who have a standard curative option for their lymphoid malignancy at current state of disease are excluded. For eligibility on this trial, allogeneic stem cell transplantation is not to be considered a standard curative option.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant females. (Lactating females must agree not to breast feed while taking carfilzomib, lenalidomide or romidepsin).
• Known hypersensitivity to thalidomide.
• The development of erythema multiforme if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Prior use of lenalidomide if discontinued due to toxicity.
• Prior therapy with romidepsin if discontinued due to toxicity.
• Prior therapy with carfilzomib if discontinued due to toxicity.
• Prior therapy with a proteasome inhibitor if discontinued due to toxicity.
• Concurrent use of other anti-cancer agents or treatments.
• Known seropositive and requiring anti-viral therapy for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Concurrent malignancy requiring active therapy.
• Patients with more than one type of lymphoma may be enrolled after discussion with the MSK Principal Investigator.
• Known central nervous system or meningeal involvement (in the absence of symptoms investigation into central nervous system involvement is not required).
• The following known cardiac abnormalities:

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• University of Nebraska: collaborator

Study Sites (6)

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7680, United States

Location

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, 11570, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma, T-Cell; Recurrence; Lymphoma

Interventions

carfilzomib; romidepsin; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

Results Point of Contact

• Title: Dr. Steve Horwitz, MD
• Organization: Memorial Sloan Kettering Cancer Center

horwitzs@MSKCC.ORG

646-608-2680

Study Officials

• Steven Horwitz, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2015
• First Posted: January 19, 2015
• Study Start: January 2, 2015
• Primary Completion: January 11, 2023
• Study Completion: January 11, 2023
• Last Updated: April 4, 2024
• Results First Posted: April 4, 2024

Record last verified: 2023-01

Locations

US (6)