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Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaPhase 1NCT02268851

A Phase I/Ib Safety and Efficacy Study of the PI3K-delta Inhibitor TGR-1202 and Ibrutinib in Patients With CLL or MCL

A Phase 1 study testing TGR-1202 and Ibrutinib in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Mantle Cell Lymphoma, run by Dana-Farber Cancer Institute at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This research study will be evaluating the safety and efficacy of a study drug called TGR-1202 in combination with a known drug ibrutinib, also known as Imbruvica, as a possible treatment for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Mantle Cell Lymphoma (MCL) that has come back or that has… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TGR-1202 and Ibrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
5 sitesUnited States
Study dates
Nov 2014to Oct 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmed diagnosis of Mantle Cell Lymphoma (MCL), Chronic Lymphocytic Leukemia (CLL), or Small Lymphocytic Lymphoma (SLL)
  • Adequate organ system function ( Absolute neutrophil count, Platelets,Bilirubin, Platelets, Aspartate transferase ,Alanine aminotransferase, Creatinine Clearance)
  • Eastern Cooperative Group (ECOG) Performance status ≤ 2
  • Ability to swallow and retain oral medication
  • Female patients: must have negative serum pregnancy test at study screening/ all male partners must consent to use a medically acceptable method of contraception
  • Willingness and ability to comply with trial and follow-up procedures, and give written informed consent

Who cannot join

  • Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization) within 3 weeks of Cycle 1/Day 1,
  • Autologous hematologic stem cell transplant within 3 months of study entry.
  • Allogeneic hematologic stem cell transplant within 12 months.
  • Post-allo patients must not have active graft versus-host disease
  • Evidence of active Hepatitis B,Hepatitis C or HIV infection.
  • Active central nervous system involvement by lymphoma
Show all 14Show fewer
  • Requires treatment with strong CYP3A4/5 inhibitors
  • Severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • QTcF >470 msec (QT interval, Fredericia calculation)
  • Angina not well-controlled by medication
  • Poorly controlled or clinically significant atherosclerotic vascular disease
  • Presence of other active cancers, or history of treatment for invasive cancer within the past 2 years.
  • Require warfarin for anticoagulation
  • Women who are pregnant or lactating

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Beth Israel Deaconness Medical Center

    Boston, Massachusetts, 02215

  • Eastern Maine Medical Center/ Northern Light Cancer Care

    Brewer, Maine, 04412

  • St. Francis Hospital and Cancer Center

    Hartford, Connecticut, 06105

  • Pacific Cancer Care

    Monterey, California, 93940

Other trials in United States

About this study

Official title: A Multi-center Phase I/Ib Study Evaluating the Efficacy and Safety of the Novel PI3k Delta Inhibitor TGR-1202 in Combination With Ibrutinib in Patients With Select B-Cell Malignancies

This research study will be evaluating the safety and efficacy of a study drug called TGR-1202 in combination with a known drug ibrutinib, also known as Imbruvica, as a possible treatment for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Mantle Cell Lymphoma (MCL) that has come back or that has not responded to standard treatment.

Read the detailed description

This research study is a Phase I and Ib combination clinical trial, which aims to both evaluate the safety of an investigational drug combination and also tries to define the appropriate dose of the investigational drug to evaluate in later clinical trials. "Investigational" means that the intervention is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved TGR-1202 in the United States for use in MCL/CLL/SLL cancers.

TGR-1202 is a newly developed drug that may stop cancer cells from growing based on recent laboratory experiments. The results from these experiments suggest this drug may help to kill cancer cells when coupled with ibrutinib. In this research study, the safety and tolerability of TGR-1202 is being investigated to determine the highest dose that can safely be used in combination with ibrutinib. The study is also aimed to evaluate whether TGR-1202 has any effect on tumor growth (nodal response), and to determine the overall repsonse rate and duration of response in patients with CLL/SLL or MCL

Being tested
TGR-1202, Ibrutinib
Keywords
Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TGR-1202Drug

    Also called RP5264, Umbralisib

    Capsules taken whole daily with water and with food

  • IbrutinibDrug

    Also called Imbruvica, CRA-032765, PCI-32765

    Capsules taken whole with water- Do not consume fish oil, vitamin E, grapefruit, or Seville oranges

Study groups in NCT02268851
Study groupRoleWhat they receive
CLLExperimentalDose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. * Each Cycle = 28 days * TGR-1202 (oral): Starting on Day 1 administered daily. * Ibrutinib (oral): Starting on Day 1 administered daily.
Receives: Drug: TGR-1202; Drug: Ibrutinib
MCLExperimentalDose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. * Each Cycle = 28 days * TGR-1202 (oral): Starting on Day 1 administered daily. * Ibrutinib (oral): Starting on Day 1 administered daily.
Receives: Drug: TGR-1202; Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I

    To assess the safety of TGR1202 in combination with ibrutinib relapsed or refractory CLL or MCL. DLT is based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. DLT refers to toxicities experienced at any time during the study treatment, defined as Grade 4 anemia; Grade 4 neutropenia lasting >7 days (while receiving growth factor support); Grade 4 thrombocytopenia lasting > 7 days; Grade ≥3 febrile neutropenia; and Grade ≥3 thrombocytopenia with Grade >2 hemorrhage;Grade ≥ 3 non-hematologic toxicity unresponsive to standard supportive care measure with the exception of asymptomatic Grade ≥3 lab abnormalities that resolve to ≤ Grade 1 or baseline within 7 days;treatment delay of ≥14 days due to unresolved toxicity; and non-hematologic toxicity of Grade 2 (at any time during treatment) that, in the judgment of the Investigators, Study Chair, and the Medical Monitor, is dose-limiting.

    Measured: Participants were assessed every week or more often as needed during Cycle 1 or more often for up to 28 days to assess Dose-limiting toxicities (DLTs) during Phase I

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on the 2008 IW-CLL criteria for CLL (Hallek et al., 2008) by Lugano Criteria ( Cheson et al,.24) for MCL.

    Measured: At baseline, End of Cycle 2, End of Cycle 5, End of Cycle 9, End of Cycle 14 and approximately q6 months until C26, then investigator discretion thereafter

  2. Rate of Nodal Partial Response With Lymphocytosis (nPR)

    nPR will only be evaluated in CLL patients, defined as percentage of patients achieved nodal PR. As per Cheson et al., 2012, patients who achieve a radiographic PR but continue to have a lymphocytosis with >5,000 B-lymphocytes per μL are considered to have a nodular partial response, also known as PR with lymphocytosis, due to the fact that they appear to derive a similar clinical benefit from BCR inhibitors as patients who achieve a traditional PR.

    Measured: At baseline, End of Cycle 2, End of Cycle 5, End of Cycle 9, End of Cycle 14 and approximately q6 months until C26, then investigator discretion thereafter

  3. Median Progression-Free Survival (PFS)

    Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last dsease assessment.

    Measured: Disease will be evaluated at baseline, cycle 1 day 1,8,15,22 and cycle 2 day 1,15, and cycle 3-6 on day1, and every 2 cycles until cycle 12, then every 3 cycles thereafter. In long-term follow-up, survival will be followed every 3 cycles up to 2 years.

  4. Median Duration of Overall Response (DOR)

    Duration of Overall Response (DOR), estimated using the Kaplan Meier method, is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) per 2008 IWCLL Criteria, until the first date that recurrent or progressive disease is objectively documented. Patients without progressive disease are censored at the date of last disease assessment.

    Measured: Disease response will be evaluated at baseline, cycle 1 day 1,8,15,22 and cycle 2 day 1,15, and cycle 3-6 on day1, and every 2 cycles until cycle 12, then every 3 cycles thereafter.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2014 (estimated)
  2. Study startNov 2014
  3. Primary completionMay 2018
  4. Study completionOct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02268851
Sponsor's protocol ID
14-396
Other IDs
TGR-IB-105
Status last verified
Sep 2024
First submitted
16 Oct 2014
Last updated
15 Nov 2024
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Davids MS, Kim HT, Nicotra A, Savell A, Francoeur K, Hellman JM, Bazemore J, Miskin HP, Sportelli P, Stampleman L, Maegawa R, Rueter J, Boruchov AM, Arnason JE, Jacobson CA, Jacobsen ED, Fisher DC, Brown JR; Blood Cancer Research Partnership of the Leukemia and Lymphoma Society. Umbralisib in combination with ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or mantle cell lymphoma: a multicentre phase 1-1b study. Lancet Haematol. 2019 Jan;6(1):e38-e47. doi: 10.1016/S2352-3026(18)30196-0. Epub 2018 Dec 14.

    PubMed 30558987

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TGR-1202 and Ibrutinib in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Mantle Cell Lymphoma, run by Dana-Farber Cancer Institute at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I (time frame: Participants were assessed every week or more often as needed during Cycle 1 or more often for up to 28 days to assess Dose-limiting toxicities (DLTs) during Phase I). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02268851, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2024.

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