A Phase II Study of AT7519M, a CDK Inhibitor, in Patients With Relapsed Mantle Cell Lymphoma

NCT01652144 | Completed Phase 2 DMC

• 1 other identifier: I194
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to find out what effects a new drug AT7519M has on mantle cell lymphoma.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Efficacy

  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 mantle cell lymphoma (MCL).

  24 months

Secondary Outcomes (3)

• Severity of toxicity

  24 months

• Time to progression

  24 months

• Response duration

  24 months

Study Arms (1)

AT7519M

EXPERIMENTAL

AT7519M: 27 mg/m2 IV injection, 1 hour infusion, 27 mg/m2/day twice weekly x 2 weeks every 3 weeks (days 1, 4, 8 and 11)

Drug: AT7519M

Interventions

AT7519M DRUG

AT7519M

Eligibility Criteria

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

You may qualify if:

• Histologically documented mantle cell lymphoma non-refractory to prior therapy. Diagnosis of mantle cell lymphoma should be confirmed by the local institution's lymphoma pathologist.
• Presence of clinically and/or radiologically documented disease. At least one site of disease must be bidimensionally measurable using CT or MRI performed in the 3 weeks prior to study enrolment. Bone lesions are not considered to be bidimensionally measurable.
• Minimum size of at least ONE lesion must be as follows: (must be done within 21 days prior to registration)
• Lymph nodes (measured by spiral CT scan) \> 1.5 cm x or 1.5 cm
• Other non-nodal lesions:
• MRI ≥ 1 cm x 1 cm CT scan ≥ 1 cm x 1 cm Physical exam ≥ 1 cm x 1 cm (e.g. skin lesion, nodules)
• Patients must have a life expectancy of at least 12 weeks.
• Age ≥ 18 years.
• ECOG performance status of 0, 1 or 2 (see Appendix II).
• Previous Therapy Patients must have received at least one, and up to three prior systemic chemotherapy regimens (high dose chemotherapy with autologous stem cell support is permitted but this must be counted as one line of therapy) but must NOT have shown disease progression while receiving chemotherapy or within 1 month of last dose of most recent therapy (i.e. must be non-refractory).
• Systemic Therapy:
• Patients must be ≥ 4 weeks since last dose of systemic therapy (including investigational). As noted, 1-3 previous chemotherapy regimens may have been given. NB: The same chemotherapy combination given for first line therapy and second line therapy is considered two regimens. 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.
• 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, or other solid tumours curatively treated with no evidence of disease for \> 5 years.
• Patients with known CNS involvement by lymphoma. Tests to investigate CNS involvement are required only if clinically indicated (i.e. disease suspected on basis of symptoms or other findings).
• 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;
• pulmonary disease requiring oxygen;
• known HIV infection or other immune deficiency;
• 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 symptomatic heart failure or angina) within 3 months of entry or any cardiac disease that, in the opinion of the investigator, increases risk for ventricular arrhythmia.
• Any personal history of ventricular arrhythmia, which was symptomatic or required treatment (CTC grade 3). This includes: multifocal PVCs, bigeminy, trigeminy, ventricular tachycardia)
• Uncontrolled hypertension (systolic blood pressure of 150 mmHg or higher or diastolic blood pressure of 95 mmHg or higher)

Sponsors & Collaborators

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

Study Sites (6)

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, 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

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, 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

Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• John Kuruvilla

  Univ. Health Network-Princess Margaret Hospital

  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: July 25, 2012
• First Posted: July 27, 2012
• Study Start: September 14, 2012
• Primary Completion: December 2, 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 (6)