Study of Phosphatidylinositol-3-kinase (PI3K) Inhibitor Idelalisib (GS-1101) in Waldenström Macroglobulinemia

Phase II Study of Phosphatidylinositol-3-kinase (PI3K) Inhibitor Idelalisib (GS-1101) in Waldenström Macroglobulinemia

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02439138

Enrollment

Registered

2015-05-08

Start date

2015-10-31

Completion date

2016-04-30

Last updated

2017-01-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Waldenstrom's Macroglobulinemia

Keywords

Waldenstrom's Macroglobulinemia

Brief summary

This research study is evaluating a drug called idelalisib (formerly known as GS-1101 or CAL-101) as a possible treatment for Waldenstrom's Macroglobulinemia (WM).

Detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug, idelalisib, to learn whether idelalisib works in treating a specific cancer. Investigational means that idelalisib is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if idelalisib is effective for treating different types of cancer. Idelalisib has already been approved in the US by the FDA to treat patients with relapsed chronic lymphocytic leukemia, follicular lymphoma and small lymphocytic lymphoma. Idelalisib is a newly discovered drug that is being developed as an anti-cancer agent. This drug has been used in laboratory experiments and other research studies in B-cell malignancies and information from those other research studies suggests that idelalisib may help to target the tumor cells in B-cell malignancies, including WM. B cells are a type of white blood cell responsible for making antibodies. In this research study, the investigators are testing the safety and efficacy of idelalisib as a treatment option for relapsed or refractory Waldenstrom's Macroglobulinemia.

Interventions

DRUGGS-1101

Oral twice daily for 6 months followed by once daily until disease progression or unacceptable toxicity.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Participants must meet the following criteria on screening examination to be eligible to participate in the study: * Clinicopathological diagnosis of Waldenstrom's Macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom's macroglobulinemia (Owen 2003; Kyle 2003). * Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of \> 2 times the upper limit of normal of each institution is required. * Have received at least one prior therapy for WM. * Age ≥18 years. * ECOG performance status \<2 (see Appendix A.). * Participants must have normal organ and marrow function as defined below: * Absolute neutrophil count \> 1,000/mm3 * Platelets \> 50,000/mm3 * Hemoglobin \> 8 g/dL * Total bilirubin ≤1.5 mg/dL or \< 2 mg/dL if attributable to hepatic infiltration by neoplastic disease * AST (SGOT) and ALT (SGPT) \< 2.5 X institutional upper limit of normal * Creatinine ≤ 2 mg/dL * Not on any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin. * Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or have or will have complete abstinence from heterosexual intercourse during the following time periods related to this study: 1\) while participating in the study; and 2) for at least 28 days after discontinuation from the study. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. FCBP must be referred to a qualified provider of contraceptive methods if needed. * Able to adhere to the study visit schedule and other protocol requirements. * Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

* Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent the participant from signing the informed consent form * Concurrent use of any other anti-cancer agents or treatments or any other study agents * Prior exposure to idelalisib * Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism or excretion of Idelalisib; or impair the assessment of study results * Grade \> 2 toxicity (other than alopecia) continuing from prior anti-cancer therapy * Known central nervous system lymphoma * Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening * New York Heart Association classification III or IV heart failure. * Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. * Known history of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV) infection * Lactating or pregnant women * Inability to swallow capsules * History of non-compliance to medical regimens * Unwilling or unable to comply with the protocol

Design outcomes

Primary

Measure	Time frame	Description
Overall Response Rate (ORR)	Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.	ORR measured by decrease in serum IgM level by at least 25% from baseline.

Secondary

Measure	Time frame	Description
Rate of Complete Response (CR)	Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.	CR measured by decrease in serum IgM levels to normal range, disappearnace of monoclonal protein by immunofixation, no evidence of bone marrow involvement, and resolution of any extramedullary disease by CT scan.
Rate of Very Good Partial Response (VGPR)	Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.	VGPR measured by decrease in serum IgM levels of at least 90% from baseline.
Rate of Partial Response (PR)	Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.	PR measured by decrease in serum IgM levels of between 25% and 50% from baseline.
Percentage of Participants With Adverse Events	Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.	Assess the safety and tolerability of idelalisib
Rate of Stable Disease	Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.	Stable disease measured by serum IgM levels \<25% reduced from baseline.
Rate of Progressive Disease	Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.	Progressive disease measured by an 25% increase in serum IgM level with an absolute increase of at least 500mg/dL from the lowest attained IgM on therapy.
Rate of Minimal Response	Participants were followed for the duration of therapy, a median of one cycle, for up to 3 cycles.	Minimal response measured by decrease in serum IgM levels of between 25% and 50%.

Countries

United States

Participant flow

Participants by arm

Arm	Count
GS-1101 After the screening procedures confirms eligibility to participate in the research study. Treatment will be administered on an outpatient basis. \-- Idelalisib (GS-11-01) orally, predetermined dose twice daily per cycle for up to 6 cycles. After this initial 6 month period, for Cycles 7 and beyond, Idelalisib will be administered once a day until disease progression. GS-1101	5
Total	5

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	PI decision to terminate the study	2

Baseline characteristics

Characteristic	GS-1101
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	3 Participants
Age, Categorical Between 18 and 65 years	2 Participants
Age, Continuous	66 years
Gender Female	1 Participants
Gender Male	4 Participants
Region of Enrollment United States	5 participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	5 / 5
serious Total, serious adverse events	4 / 5