A Phase II Study of AT7519M, a CDK Inhibitor, in Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia

NCT01627054 | Completed Phase 2 DMC

• 1 other identifier: I193
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to find out what effects a new drug AT7519M has on chronic lymphocytic leukemia.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Efficacy (as assessed by objective response rate) of AT7519M when given as a 1 hour intravenous infusion twice weekly for two out of three weeks in patients with relapsed and/or refractory chronic lymphocytic leukemia.

  24 months

Secondary Outcomes (3)

• Toxicity severity

  24 months

• Time to progression

  24 months

• Response duration

  24 months

Study Arms (1)

AT7519M

EXPERIMENTAL

Drug: AT7519M

Interventions

AT7519M DRUG

Dose: 27 mg/m2, IV injection, 1 hour infusion Schedule: 27 mg/m2/day twice weekly x 2 weeks every 3 weeks (days 1, 4, 8 and 11)

AT7519M

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously documented CLL as defined by the 2008 International Workshop on Chronic Lymphocytic Leukemia guidelines \[Hallek 2008(a)\], that is recurrent or relapsed after previous therapy and that requires treatment.
• Patients must have a life expectancy of at least 12 weeks.
• Age ≥ 18 years.
• ECOG performance status of 0, 1 or 2
• Measurable disease criteria to assess response. Patients must have at least ONE of:
• Absolute lymphocyte count ≥ 10 x 10\^9/L OR At least one pathologically enlarged lymph node (≥ 2 x 2 cm) by CT scan
• Previous Therapy Patients must have received at least one, and may have received up to three prior systemic treatment regimens (single agent or combination therapy), there is no limit on number of prior regimens.
• Systemic Therapy:
• Patients must have received at least one prior systemic treatment regimen (single agent or combination therapy). There is no limit on number of prior regimens.
• Patients must be ≥ 4 weeks since last dose of systemic therapy (including investigational). Exceptions to the 4-week interval since last treatment are possible if prior therapy is non-myelosuppressive or if any treatment-related myelosuppression has resolved.
• Rationale:
• Based on a review of recently published phase II trials of CDK inhibitors in relapsed and refractory CLL, there does not appear to be sufficient grounds to restrict the number of previous cycles of systemic chemotherapy. The IND193 investigators do not predict that this change will affect either the safety or efficacy outcomes of the study drug.
• Not permitted:
• Radioactive Monoclonal Antibody Therapy
• Prior treatment with AT7519M or another CDK inhibitor

You may not qualify if:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, other in situ cancers or other invasive malignancies curatively treated with no evidence of disease for ≥ 5 years.
• Patients with known CNS involvement by CLL. Tests to investigate CNS involvement are required only if clinically indicated (i.e. disease suspected on basis of symptoms or other findings).
• Patients with clinically suspected or proven progression to high grade lymphoma (Richter's transformation) or myelodysplasia.
• Patients with known hypersensitivity to the study drug or its components.
• Pregnant or lactating women. (N.B.: All women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to registration).
• Men and women of childbearing potential who do not agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of the study participation. (Should a woman become pregnant or suspect she is pregnant, or should a man father a child, while participating in this study, she/he should inform the treating physician immediately.)
• Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including, but not limited to:
• history of significant neurologic or psychiatric disorder (e.g. uncontrolled psychotic disorders) which would impair the ability to obtain consent or limit compliance with study requirements;
• active uncontrolled or serious infection (viral, bacterial or fungal);
• pulmonary disease requiring oxygen;
• known HIV infection or other immune deficiency disorders (except for CLL);
• other medical conditions that might be aggravated by study treatment
• Patients with pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction as follows:
• Significant cardiac event (including heart failure or ischemia) within 3 months of entry or any cardiac disease that, in the opinion of the investigator, increases risk for ventricular arrhythmia
• Any family or personal history of ventricular arrhythmia, which was symptomatic or required treatment (CTC grade 3). This includes: multifocal PVCs, bigeminy, trigeminy, ventricular tachycardia)

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• Astex Pharmaceuticals, Inc.: collaborator

Study Sites (3)

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Seftel MD, Kuruvilla J, Kouroukis T, Banerji V, Fraser G, Crump M, Kumar R, Chalchal HI, Salim M, Laister RC, Crocker S, Gibson SB, Toguchi M, Lyons JF, Xu H, Powers J, Sederias J, Seymour L, Hay AE. The CDK inhibitor AT7519M in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma. A Phase II study of the Canadian Cancer Trials Group. Leuk Lymphoma. 2017 Jun;58(6):1358-1365. doi: 10.1080/10428194.2016.1239259. Epub 2016 Oct 17.

  PMID: 27750483 RESULT

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Matthew D Seftel

  Cancer Care Manitoba, Winnipeg Manitoba Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2012
• First Posted: June 25, 2012
• Study Start: August 27, 2012
• Primary Completion: March 21, 2014
• Study Completion: February 13, 2015
• Last Updated: August 4, 2023

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)