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

NCT02867618 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: AAAP5661
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Hodgkin Disease; Lymphoma, Non-hodgkin

Outcome Measures

Primary Outcomes (2)

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

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

  9 months

• Objective Response Rate (ORR) (Phase 2)

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

  9 months

Study Arms (1)

Carfilzomib + TGR-1202

EXPERIMENTAL

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.

Drug: Carfilzomib; Drug: TGR-1202

Interventions

Carfilzomib DRUG

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

Also known as: Kyprolis

Carfilzomib + TGR-1202

TGR-1202 DRUG

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

Also known as: (formerly) RP-5264

Carfilzomib + TGR-1202

Eligibility Criteria

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

You may qualify if:

• 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

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 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

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Irving Medical Center - Center for Lymphoid Malignancies

New York, New York, 10019, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

carfilzomib; umbralisib; rhoA GTP-Binding Protein

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

rho GTP-Binding Proteins; Monomeric GTP-Binding Proteins; GTP-Binding Proteins; GTP Phosphohydrolases; Acid Anhydride Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Intracellular Signaling Peptides and Proteins

Results Point of Contact

• Title: Ana Ignat
• Organization: Columbia University

ai2111@cumc.columbia.edu

212-305-3612

Study Officials

• Changchun Deng, MD

  Assistant Professor of Clinical Medicine and Experimental Therapeutics

  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: August 9, 2016
• First Posted: August 16, 2016
• Study Start: October 16, 2016
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: July 16, 2021
• Results First Posted: July 16, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)