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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02867618
Recruitment Status : Recruiting
First Posted : August 16, 2016
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
Changchun Deng, Columbia University

Study Description
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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.


Condition or disease Intervention/treatment Phase
Hodgkin Disease Lymphoma, Non-hodgkin Drug: Carfilzomib Drug: TGR-1202 Phase 1 Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Carfilzomib and a PI3Kdelta Inhibitor TGR-1202 in the Treatment of Patients With Relapsed or Refractory Lymphoma
Actual Study Start Date : October 16, 2016
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Carfilzomib

Arms and Interventions
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Arm Intervention/treatment
Experimental: Carfilzomib + TGR-1202
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
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
Other Name: Kyprolis

Drug: TGR-1202
Oral TGR-1202 will be given PO once daily on Days 1-28 . This will be given in combination with the intravenous Carfilzomib
Other Name: (formerly) RP-5264


Outcome Measures
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Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) (Phase 1) [ Time Frame: 9 months ]
    The highest dose of the study treatment that does not cause unacceptable side effects.

  2. Objective Response Rate (ORR) (Phase 2) [ Time Frame: 9 months ]
    Defined as best response (complete response and partial response) by 4 cycles.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  1. 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.
  2. History of allergic reactions to TGR-1202 or carfilzomib
  3. Uncontrolled inter-current illness
  4. Pregnant women
  5. Nursing women
  6. Current malignancy or history of a prior malignancy
  7. Patient known to be Human Immunodeficiency Virus (HIV)-positive
  8. Active Hepatitis A, Hepatitis B, or Hepatitis C infection
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02867618


Contacts
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Contact: Changchun Deng, MD, PhD (212) 326-5720 cd2448@cumc.columbia.edu

Locations
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United States, New York
Columbia University Irving Medical Center - Center for Lymphoid Malignancies Recruiting
New York, New York, United States, 10019
Contact: Freddy Loffredo    212-326-5720    fl2156@cumc.columbia.edu   
Principal Investigator: Changchun Deng, M.D., PhD         
Sponsors and Collaborators
Changchun Deng
Investigators
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Principal Investigator: Changchun Deng, MD Assistant Professor of Clinical Medicine and Experimental Therapeutics
More Information
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Responsible Party: Changchun Deng, Assistant Professor of Clinical Medicine and Experimental Therapeutics, Columbia University
ClinicalTrials.gov Identifier: NCT02867618    
Other Study ID Numbers: AAAP5661
First Posted: August 16, 2016    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Hodgkin Disease
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases