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Completed

NCT Number: NCT04038359

A Phase 2 Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Participants With Indolent Non-Hodgkin Lymphoma

This study examined the effects of predefined 2-week duvelisib dose holidays on tumor responses and safety/tolerability.

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Key information

Conditions

Indolent Non-hodgkin Lymphoma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

FN Hradec Kralove, Hradec Králové, Czechia

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About this study

This was a Phase 2, randomized, open-label, 2-arm study designed to evaluate the efficacy and safety of prescribed drug holidays of duvelisib treatment in participants with relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) who have received at least 1 prior systemic therapy.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Eastern Cooperative Oncology Group performance status ≤ 2
  • Histologically confirmed diagnosis of iNHL (subtypes include follicular lymphoma [FL] Grades 1 to 3a), marginal zone lymphoma (splenic, nodal, or extranodal), or small lymphocytic lymphoma
  • Must have received 1 prior systemic regimen for iNHL
  • Must have documented radiologic evidence of disease progression, at least 1 bi-dimensionally measurable lesion ≥ 1.5 centimeters (which has not been previously irradiated), according to 2007 revised International Working Group criteria, and be a candidate for a subsequent line of therapy.
  • Must have adequate organ function defined by the following laboratory parameters:
  • Absolute neutrophil count ≥ 1.0 × 10^9/liter (L)
  • Platelet count ≥ 75 × 10^9/L
  • Hemoglobin ≥ 8 grams/deciliter
  • Estimated creatinine clearance ≥ 60 milliliters/minute, as determined by the Cockcroft-Gault method
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (exception: participants with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN)
  • Aspartate transaminase/serum glutamic-oxaloacetic transaminase and alanine aminotransferase/serum pyruvic transaminase ≤ 3.0 × ULN

Exclusion criteria

  • Anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of study intervention; palliative radiation therapy is allowed if > 7 days before planned first dose of study interventions, and any toxicity is Grade ≤ 1
  • Clinical or histological evidence of transformation to a more aggressive subtype of lymphoma or grade 3b FL or Richters' transformation or chronic lymphocytic leukemia
  • Prior allogeneic hematopoietic stem cell transplant; prior treatment with a PI3K inhibitor
  • History of drug-induced colitis or pneumonitis; tuberculosis treatment ≤ 2 years prior to randomization; administration of a live or live attenuated vaccine within 6 weeks of randomization
  • Ongoing treatment with chronic immunosuppressants or systemic steroids or treatment for systemic bacterial, fungal, or viral infection
  • Active cytomegalovirus or Epstein-Barr virus infection
  • Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus, or herpes zoster at screening
  • Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A. No prior use within 2 weeks before the start of study intervention.
  • Baseline QT interval corrected with Fridericia's method > 500 milliseconds
  • Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix, bladder cancer, or prostate cancer not requiring treatment. Participants with previous malignancies are eligible if they have been disease-free for 2 years or more.
  • Unstable or severe uncontrolled medical condition that would, in the Investigator's judgment, increase the participant's risk to participating in this study.

Treatment and study plan

Duvelisib

Drug

Phosphoinositide 3-kinase (PI3K) inhibitor

Other names: Copiktra, VS-0145, IPI-145

Primary outcomes

  1. Overall Response Rate (ORR) According to the 2007 Revised International Working Group (IWG) Criteria

    Time frame: Up to 14 months

    ORR was defined as the percentage of participants achieving a complete response (CR) or partial response (PR) and assessed using the 2007 revised IWG criteria. The 2007 revised IWG criteria defined CR as the disappearance of all evidence of disease and PR as the regression of measurable disease and no new sites.

Secondary outcomes

  1. Progression-free Survival (PFS)

    Time frame: Up to 2 years

    PFS was defined as the time from first dose to first progressive disease (PD) or death (progression date/death date - treatment start date + 1) or, for participants without PD or documented death, as the time from first dose to censoring date (censoring date - treatment start date + 1). The 2007 revised IWG criteria defined PD as any new lesion or increase by ≥50% of previously involved sites from nadir. The 2014 Lugano criteria defined PD as a progressive metabolic response (according to positron emission tomography-computed tomography [PET-CT]) and progressive disease (according to computed tomography [CT]). Results reported as months.

  2. ORR At Specific Timepoints

    Time frame: 6, 12, 18, and 24 months after first dose of study intervention

    ORR at 6, 12, 18, and 24 months after first dose of study intervention was defined as the percentage of participants achieving CR or PR at each timepoint and was assessed using both the 2007 revised IWG criteria and the 2014 Lugano criteria. The 2007 revised IWG criteria defined CR as the disappearance of all evidence of disease and PR as the regression of measurable disease and no new sites. The 2014 Lugano criteria defined CR as a complete metabolic response (according to PET-CT) and a complete radiologic response (according to CT) and PR as partial metabolic response (according to PET-CT) and partial remission (according to CT). The response was cumulative for each timepoint; a participant was considered a responder if their first response occurred up to the end of that timepoint.

  3. Duration of Response (DOR)

    Time frame: Up to 2 years

    DOR was defined for participants with CR or PR as the time from the date of first documentation of response (CR or PR) to date of the first documentation of PD or death. The 2007 revised IWG criteria defined CR as the disappearance of all evidence of disease, PR as the regression of measurable disease and no new sites, and PD as any new lesion or increase by ≥50% of previously involved sites from nadir. The 2014 Lugano criteria defined CR as a complete metabolic response (according to PET-CT) and a complete radiologic response (according to CT), PR as partial metabolic response (according to PET-CT) and partial remission (according to CT), and PD as a progressive metabolic response (according to PET-CT) and progressive disease (according to CT). Results are reported as months.

  4. Overall Survival (OS)

    Time frame: Up to 2 years

    OS was the time from first dose to death (death date - treatment start date + 1). Participants without documented death were censored at their last known alive date (last known alive date - treatment start date + 1). Results reported as months.

  5. Lymph Node Response Rate (LNRR)

    Time frame: 14 months

    LNRR was calculated as the percentage of participants achieving ≥50% decrease in the sum of the product of the diameters of target lymph nodes. The confidence interval for LNRR was calculated only for participants who had at least 1 nodal target lesion, using the Clopper-Pearson exact method for binomial proportions. Participants whose target lesions were all extranodal were excluded from this analysis.

  6. Time To First Response (TTFR)

    Time frame: Up to 14 months

    For participants with CR or PR, TTFR was defined as the time from first dose of study intervention to time of first CR or PR and was calculated as: the date of first CR or PR - randomization date + 1. The 2007 revised IWG criteria defined CR as the disappearance of all evidence of disease and PR as the regression of measurable disease and no new sites. The 2014 Lugano criteria defined CR as a complete metabolic response (according to PET-CT) and a complete radiologic response (according to CT) and PR as partial metabolic response (according to PET-CT) and partial remission (according to CT). Results are reported as months.

  7. Time To Treatment Failure (TTF)

    Time frame: Up to 2 years

    TTF was calculated as the time from first dose of study treatment to discontinuation for any reason (discontinuation date - treatment start date + 1). Participants who were still ongoing treatment at time of data cut were censored (last dose date - treatment start date + 1). Results reported as months.

  8. ORR According to 2014 Lugano Criteria

    Time frame: Up to 14 months

    ORR was defined as the percentage of participants achieving a CR or PR and was assessed using the 2014 Lugano criteria. The 2014 Lugano criteria defined CR as a complete metabolic response (according to PET-CT) and a complete radiologic response (according to CT) and PR as partial metabolic response (according to PET-CT) and partial remission (according to CT).

Sponsors and collaborators

Lead sponsor

SecuraBio

Industry

Registry information

Official study title

A Phase 2, Randomized, Open-label, 2-Arm Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects With Indolent Non-Hodgkin Lymphoma (iNHL)

Acronym: TEMPO

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Jul 30, 2019
Registry last updated
Sep 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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