A Phase 2 Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects With Indolent Non-Hodgkin Lymphoma. (TEMPO)

• ClinicalTrials.gov Identifier: NCT04038359
• Recruitment Status: Recruiting
• First Posted: July 30, 2019
• Last Update Posted: October 3, 2019
• Sponsor: Verastem, Inc.
• Information provided by (Responsible Party): Verastem, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Indolent Non-hodgkin Lymphoma	Drug: Duvelisib	Phase 2

Detailed Description:

This is a Phase 2, randomized, open-label, 2 arm study designed to evaluate the efficacy and safety of prescribed drug holidays of duvelisib treatment in subjects with R/R iNHL who have received at least 1 prior systemic therapy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official 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) (TEMPO)
• Actual Study Start Date: September 24, 2019
• Estimated Primary Completion Date: May 30, 2022
• Estimated Study Completion Date: July 29, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Duvelisib, Continuous and Intermittent Dosing; Duvelisib 25 mg BID continuously for 10 weeks, followed by 25 mg BID dosed two weeks on and two weeks off of each subsequent 4-week cycles.	Drug: Duvelisib; PI3K Inhibitor; Other Name: Copiktra, VS-0145
Experimental: Duvelisib, Intermittent Dosing; Duvelisib 25 mg BID dosed two weeks on and two weeks off.	Drug: Duvelisib; PI3K Inhibitor; Other Name: Copiktra, VS-0145

Outcome Measures

Primary Outcome Measures :

1. ORR (Objective Response Rate) [ Time Frame: 36 months ]
   Proportion of subjects achieving a CR or PR will be estimated as per IWG Criteria.

Secondary Outcome Measures :

1. PFS (Progression Free Survival) [ Time Frame: 5 years ]
   From time of first dose of study intervention to PD or death.
2. ORR (Objective Response Rate) [ Time Frame: ORR estimated at 6, 12, 18, and 24 months after first dose of study intervention. ]
   Proportion of subjects achieving a CR or PR will be estimated as per Lugano Criteria
3. DOR (Duration of Response) [ Time Frame: 5 years ]
   From the time of first response to PD using KM methods.
4. OS (Overall Survival) [ Time Frame: 5 years ]
   From time of first dose of study intervention to death.
5. LNRR (Lymph Node Response Rate) [ Time Frame: 36 months ]
   LNRR will be calculated as the proportion of subjects achieving ≥ 50% decrease in the SPD of target lymph nodes.
6. TTFR (Time To First Relapse) [ Time Frame: 36 months ]
   From the time of first dose of study intervention to time of first CR or PR.
7. Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0 [ Time Frame: 36 months ]
   From the time of screening to the end of Safety Follow-Up period of the study.
8. Peak Plasma Concentration (Cmax) [ Time Frame: 36 months ]
9. TTF (Time To Treatment Failure) [ Time Frame: 5 years ]
   From first dose of study intervention until discontinuation for any reason and will be summarized using KM methods.
10. Area under the plasma concentration versus time curve (AUC) [ Time Frame: 36 months ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Age ≥ 18 years, ECOG performance status ≤ 2
• Histologically confirmed diagnosis of iNHL (Subtypes include FL Grades 1 to 3a, marginal zone lymphoma (splenic, nodal, or extranodal), or SLL
• Must have received 1 prior systemic regimen for iNHL
• Must have documented radiologic evidence of disease progression, and at least 1 bi-dimensionally measurable lesion ≥ 1.5 cm (which has not been previously irradiated), according to 2007 revised IWG criteria

• Must have adequate organ function defined by the following laboratory parameters:

  • Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
  • Platelet count ≥ 75 × 10^9/L
  • Serum creatinine < 2.0 mg/dL (197 µmol/L)
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (exception: subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN)
  • Aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum pyruvic transaminase (SGPT) ≤ 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 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 CLL
• Prior allogeneic hematopoietic stem cell transplant (HSCT); treatment with a PI3K inhibitor
• History of drug-induced colitis or pneumonitis; TB 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 (CMV) or Epstein-Barr virus (EBV) infection
• Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
• Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A (CYP3A). No prior use within 2 weeks before the start of study intervention.
• Baseline QTcF > 500 ms
• Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix, bladder cancer, or prostate cancer not requiring treatment. Subjects 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 subject's risk to participating in this study.

Contacts and Locations

Contacts

Contact: Gloria Patrick; 781-469-1594; gpatrick@verastem.com

Contact: Deborah Llyod; 781-469-1583; dlloyd@verastem.com

Locations

United States, Florida

Mid-Florida Cancer Centers; Recruiting

Orange City, Florida, United States, 32763

Contact: Kiran Penta 407-607-3018 kiran@clorene.org

Sponsors and Collaborators

Verastem, Inc.

Investigators

• Study Director: Alena Zalutskaya, MD, PhD; Verastem, Inc.

More Information

• Responsible Party: Verastem, Inc.
• ClinicalTrials.gov Identifier: NCT04038359 History of Changes
• Other Study ID Numbers: VS-0145-229
• First Posted: July 30, 2019
• Last Update Posted: October 3, 2019
• Last Verified: October 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Verastem, Inc.:

PI3K Inhibitor

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; TEMPO; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs