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Carfilzomib and TGR-1202 in Treatment of R/R Lymphoma

Primary Purpose

Hodgkin Disease, Lymphoma, Non-hodgkin

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Carfilzomib

TGR-1202

About this trial

This is an interventional treatment trial for Hodgkin Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Target Population Phase I: Patients with relapsed or refractory NHL and HL Phase II: Patients with relapsed or refractory NHL

Inclusion Criteria:

Phase I: Patients must have histologically confirmed R/R NHL or HL (defined by World Health Organization (WHO) criteria). Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are eligible. In addition, patients with NHL other than diffuse large B cell lymphomas (DLBCL) must have received at least 2 prior therapies. Patients with DLBCL and HL will be eligible if there is no available standard therapy.
Phase II: Patients must have histologically confirmed R/R NHL (as defined by WHO criteria). Patients with NHL other than diffuse large B cell lymphomas (DLBCL) must have received at least 2 prior therapies. Patients with DLBCL will be eligible if there is no available standard therapy.
Must have received front line chemotherapy. No upper limit for the number of prior therapies
Evaluable Disease in the Phase I, and measurable disease in the Phase II
Age > 18 years
Eastern Cooperative Oncology Group (ECOG) performance status < 2
Patients must have adequate organ and marrow function
Adequate Contraception
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 investigational agents are allowed.
History of allergic reactions to TGR-1202 or carfilzomib
Uncontrolled inter-current illness
Pregnant women
Nursing women
Current malignancy or history of a prior malignancy
Patient known to be Human Immunodeficiency Virus (HIV)-positive
Active Hepatitis A, Hepatitis B, or Hepatitis C infection

Sites / Locations

Columbia University Irving Medical Center - Center for Lymphoid Malignancies

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Carfilzomib + TGR-1202

Arm Description

Oral TGR-1202 will be given PO once daily on Days 1-28 and carfilzomib given intravenously twice a week for 3 consecutive weeks, on days 1, 2, 8, 9, 15, and 16 on the 28-day cycle.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) (Phase 1) - TGR-1202 Only

The highest dose of the study treatment that does not cause unacceptable side effects.

Objective Response Rate (ORR) (Phase 2)

Defined as best response (complete response and partial response) by 4 cycles.

Secondary Outcome Measures

Full Information

NCT ID

NCT02867618

First Posted

August 9, 2016

Last Updated

June 28, 2021

Sponsor

Columbia University

1. Study Identification

Unique Protocol Identification Number

NCT02867618

Brief Title

Carfilzomib and TGR-1202 in Treatment of R/R Lymphoma

Official Title

Phase I/II Study of Carfilzomib and a PI3Kdelta Inhibitor TGR-1202 in the Treatment of Patients With Relapsed or Refractory Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Terminated

Why Stopped

PI left institution

Study Start Date

October 16, 2016 (Actual)

Primary Completion Date

June 30, 2020 (Actual)

Study Completion Date

June 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Columbia University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is an open label, phase I/II, dose-escalation study in the initial phase I followed by a 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 TGR-1202 and carfilzomib in participants with relapsed and refractory (R/R) non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). The safety and toxicity of this combination will be evaluated throughout the entire study. If the combination of TGR-1202 and carfilzomib 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 TGR-1202 and carfilzomib for participants with R/R NHL.

Detailed Description

Dysregulated c-Myc is associated with resistance to chemotherapy and poor survival in aggressive lymphomas. Novel strategies that target this biology could markedly improve the outcome of these participants. To date no drugs that directly target Myc have been approved for cancer treatment. Recent results by Deng et al. (Blood. 2017 Jan 5. PMID: 27784673) described a highly synergistic regimen discovered in preclinical models, through combining TGR-1202, an investigational drug that inhibits PI3K delta, and carfilzomib, a drug approved by the FDA for multiple myeloma. Importantly, the combination of TGR-1202 and carfilzomib acts by potently silencing the translation of c-Myc and inducing apoptosis in many cell lines and primary lymphoma cells representing broad histological subtypes of lymphoma. These results suggest that TGR-1202 and carfilzomib may be highly effective in relapsed and refractory lymphoma where c-Myc plays a key pathological role.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hodgkin Disease, Lymphoma, Non-hodgkin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Carfilzomib + TGR-1202

Arm Type

Experimental

Arm Description

Oral TGR-1202 will be given PO once daily on Days 1-28 and carfilzomib given intravenously twice a week for 3 consecutive weeks, on days 1, 2, 8, 9, 15, and 16 on the 28-day cycle.

Intervention Type

Drug

Intervention Name(s)

Carfilzomib

Other Intervention Name(s)

Kyprolis

Intervention Description

Carfilzomib given intravenously twice a week for 3 consecutive weeks, on days 1, 2, 8, 9, 15, and 16 on the 28-day cycle. This will be in combination with the oral TGR-1202

Intervention Type

Drug

Intervention Name(s)

TGR-1202

Other Intervention Name(s)

(formerly) RP-5264

Intervention Description

Oral TGR-1202 will be given PO once daily on Days 1-28 . This will be given in combination with the intravenous Carfilzomib

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD) (Phase 1) - TGR-1202 Only

Description

The highest dose of the study treatment that does not cause unacceptable side effects.

Time Frame

9 months

Title

Objective Response Rate (ORR) (Phase 2)

Description

Defined as best response (complete response and partial response) by 4 cycles.

Time Frame

9 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Target Population Phase I: Patients with relapsed or refractory NHL and HL Phase II: Patients with relapsed or refractory NHL Inclusion Criteria: Phase I: Patients must have histologically confirmed R/R NHL or HL (defined by World Health Organization (WHO) criteria). Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are eligible. In addition, patients with NHL other than diffuse large B cell lymphomas (DLBCL) must have received at least 2 prior therapies. Patients with DLBCL and HL will be eligible if there is no available standard therapy. Phase II: Patients must have histologically confirmed R/R NHL (as defined by WHO criteria). Patients with NHL other than diffuse large B cell lymphomas (DLBCL) must have received at least 2 prior therapies. Patients with DLBCL will be eligible if there is no available standard therapy. Must have received front line chemotherapy. No upper limit for the number of prior therapies Evaluable Disease in the Phase I, and measurable disease in the Phase II Age > 18 years Eastern Cooperative Oncology Group (ECOG) performance status < 2 Patients must have adequate organ and marrow function Adequate Contraception 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 investigational agents are allowed. History of allergic reactions to TGR-1202 or carfilzomib Uncontrolled inter-current illness Pregnant women Nursing women Current malignancy or history of a prior malignancy Patient known to be Human Immunodeficiency Virus (HIV)-positive Active Hepatitis A, Hepatitis B, or Hepatitis C infection

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Changchun Deng, MD

Organizational Affiliation

Assistant Professor of Clinical Medicine and Experimental Therapeutics

Official's Role

Principal Investigator

Facility Information:

Facility Name

Columbia University Irving Medical Center - Center for Lymphoid Malignancies

City

New York

State/Province

New York

ZIP/Postal Code

10019

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Carfilzomib and TGR-1202 in Treatment of R/R Lymphoma

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