Ph1 Volasertib Plus Romidepsin in R/R PTCL and CTCL

NCT02757248 | Withdrawn Phase 1 DMC

• 1 other identifier: Pro00060068
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase I study of the combination of volasertib and romidepsin in patients with relapsed/refractory peripheral T cell lymphoma (PTCL) or stage IIB-IV cutaneous T cell lymphoma (CTCL). This study will determine the maximum tolerated dose (MTD) of this combination by treating cohorts of patients at a certain dose combination. The investigators will use a Bayesian design to determine the dose combination for the next cohort of patients and to determine the MTD. Overall response rate as well as adverse events will be monitored and reported.

Conditions

PTCL; CTCL

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Determine the maximum tolerated dose (MTD) of the combination of romidepsin and volasertib in patients with relapsed/refractory peripheral T cell and cutaneous T cell lymphoma.

  12 months or until 2 DLTs are experienced in a cohort

Secondary Outcomes (3)

• Overall Response Rate

  24 months

• Gene Expression Signature

  60 months

• Gene Mutation Analysis

  60 months

Study Arms (5)

Cohort 1

EXPERIMENTAL

Volasertib 75mg/m2 on days 1 and 8 Romidepsin 12mg/m2 on days 1, 8 and 15

Drug: Volasertib; Drug: Romidepsin

Cohort 2

EXPERIMENTAL

Volasertib 100mg/m2 on days 1 and 8 Romidepsin 12mg/m2 on days 1, 8 and 15

Drug: Volasertib; Drug: Romidepsin

Cohort 3

EXPERIMENTAL

Volasertib 100mg/m2 on days 1 and 8 Romidepsin 14mg/m2 on days 1, 8 and 15

Drug: Volasertib; Drug: Romidepsin

Cohort 4

EXPERIMENTAL

Volasertib 150mg/m2 on days 1 and 8 Romidepsin 14mg/m2 on days 1, 8 and 15

Drug: Volasertib; Drug: Romidepsin

Cohort -1

EXPERIMENTAL

Volasertib 50mg/m2 on days 1 and 8 Romidepsin 10mg/m2 on days 1, 8 and 15

Drug: Volasertib; Drug: Romidepsin

Interventions

Volasertib DRUG

Volasertib 75-150mg/m2 given intravenously on days 1 and 8

Cohort -1; Cohort 1; Cohort 2; Cohort 3; Cohort 4

Romidepsin DRUG

Romidepsin 12-14mg/m2 given intravenously on days 1, 8 and 15

Cohort -1; Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

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

You may qualify if:

• A) Patients with a relapsed/refractory peripheral T cell lymphoma. Patients must have received at least one prior standard cytotoxic regimen such as CHOP or EPOCH OR B) Patients with relapsed/refractory stage IIb-IV cutaneous T cell lymphoma who have received at least one standard systemic treatment such as extracorporeal photopheresis, bexarotene or interferon.
• Age \> 18 years old
• Eastern Cooperative Oncology Group performance status of \<2
• Evidence of measurable or evaluable disease
• Patients must have recovered from all clinically relevant toxicities related to prior anticancer therapies to ≤ grade 2 (CTCAE v 4.03). Exception to this criterion: patients with any grade of alopecia are allowed to enter the treatment.
• Platelets \>100 x 109/L
• ANC\>1.5 x 109/L
• AST/ALT \<3.0 x institutional ULN, except for people with liver involvement by their lymphoma, who may be included if AST/ALT \<5 x ULN.
• Total Bilirubin \< 1.5 x ULN, except for patients with gilbert's syndrome who may be included if total bilirubin \< 3.0 x ULN and direct bilirubin \< 1.5 x ULN
• The following laboratory values must be greater than the lower limits of normal prior to starting study drug (supplementation allowed): potassium, magnesium
• Calculated or measured CrCl\> 30ml/min (Appendix: 3)
• Ability to provide written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.

You may not qualify if:

• Prior Treatment:
• Patients must not have received chemotherapy, radiation or surgical resection of malignancy within 3 weeks prior to the start of study drug. However, if they have received nitrosurea or mitomycin C then they should not be enrolled in the study until 6 weeks after therapy was last received.
• No limitations to number of prior therapies.
• Prior treatment with volasertib or any PLK1 inhibitor
• Prior treatment with a histone deacetylase inhibitor (anti-epileptics ok)
• Active, uncontrolled, serious infection or medical or psychiatric illness likely to interfere with participation in this clinic trial
• Known HIV infection.
• Active or chronic hepatitis B infection.
• Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the past 6 months.
• Pregnant or breast feeding. Treatment under this protocol would expose an unborn child to significant risks.
• Women and men of reproductive potential who are unwilling or unable to use an effective means of birth control during the study and for 3 months after receiving study drug.
• Major surgery within the four weeks prior to initiating protocol therapy.
• Diagnosis or treatment for any malignancy other than NHL within the 3 years preceding Day 1 of the protocol therapy. Exceptions are:
• Basal or squamous cell carcinoma of the skin
• In situ malignancy that has been completely resected.

Sponsors & Collaborators

• Anne Beaven, MD: lead
• National Comprehensive Cancer Network: collaborator
• Boehringer Ingelheim: collaborator

MeSH Terms

Interventions

BI 6727; romidepsin

Study Officials

• Anne w Beaven, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: May 2, 2016
• Study Start: November 1, 2016
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: December 1, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share