Phase 1-2 of Azacitidine + Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML)

Acute Myeloid Leukemia (AML) Clinical Trial

Official title:

A Phase 1-2 Study of Azacitidine in Combination With Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00890929
• Other study ID #: IRB-15611
• Secondary ID: SU-04242009-2385
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2009
• Est. completion date: June 2012

Study information

• Verified date: May 2018
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study has a phase 1 and a phase 2 component.

In phase 1, the objective is to determine the maximum tolerated dose (MTD) of lenalidomide when after azacitidine.

In phase 2, the objective is to determine the efficacy of the combination treatment.

Description:

The treatment regimen in this study is 7 day courses of azacitidine 75 mg/m2 followed by a 21-day courses of lenalidomide. For the primary objective, each 28-day cycle was repeated for a total of up to 6 cycles. Study completion was defined as 18 cycles of treatment, disease progression, or death.

In phase 1, the objective was to determine the maximum tolerated dose (MTD) of lenalidomide 5 mg, 10 mg, 25 mg or 50 mg, when administered after azacitidine.

In phase 2, the objective was to assess the efficacy of MTD lenalidomide administered after azacitidine, in up to six 28-day cycles.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: June 2012
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria

• WHO-confirmed acute myeloid leukemia (AML), except acute promyelocytic leukemia (APL)

• White blood cell count (WBC) at initiation of treatment = 10,000

?If WBC is > 10,000 patients may be started on an appropriate dose of hydroxyurea (to be determined by the investigators), until WBC < 10,000, at which time the hydroxyurea will be discontinued for 24 hours prior to enrollment

• Age = 60 years and not a candidate for allogeneic stem cell transplantation

• Unwilling or unable to receive conventional chemotherapy

• No prior therapy, except supportive care measures such as growth factor support, blood product transfusions, apheresis, or hydroxyurea

• ECOG performance status = 2

• Life expectancy > 2 months

• All study participants must be registered into the mandatory RevAssist® program, and must be willing and able to comply with the requirements of RevAssist

• If a female of childbearing potential (FCBP):

• Must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 to 14 days prior to study enrollment and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days)

• Must commit to either continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control, one highly effective method and one additional effective method at the same time, at least 28 days before starting lenalidomide.

• Must also agree to ongoing pregnancy testing.

• Male partners must use a latex condom during sexual contact, including if the male partners has previously had a successful vasectomy.

• Able to adhere to the study visit schedule and other protocol requirements

• Willing and able to understand and voluntarily sign a written informed consent

Exclusion Criteria

• Relapsed or refractory disease

• Prior therapy with lenalidomide

• History of intolerance to thalidomide or development of erythema nodosum while taking thalidomide or similar drugs

• Known or suspected hypersensitivity to azacitidine or mannitol

• Advanced malignant hepatic tumors

• Concomitant treatment with other anti-neoplastic agents, except hydroxyurea

• Anti-neoplastic treatment less than four weeks prior to enrollment, except hydroxyurea

• Use of any other experimental drug or therapy within 28 days of baseline

• Inability to swallow or absorb drug

• Active opportunistic infection or treatment for opportunistic infection within four weeks of first day of study drug dosing

• New York Heart Association Class III or IV heart failure

• Unstable angina pectoris

• Uncontrolled cardiac arrhythmia

• Uncontrolled psychiatric illness that would limit compliance with requirements

• Known HIV infection

• If female:

• Pregnant

• Breast-feeding females, if they do not agree to not breastfeed while taking lenalidomide

• Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation

• Laboratory abnormalities:

• Creatinine = 1.5 mg/dL

• Creatinine clearance = 50 mL/min

• Total bilirubin > 1.5 x institutional upper limit of normal (ULN), except documented Gilbert's syndrome

• AST > 2.5 x institutional ULN

• ALT > 2.5 x institutional ULN

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Adult Acute Myeloblastic Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Lenalidomide
5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
• Azacitidine
75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Celgene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compete Remission (CR) Rate	Compete Remission (CR) includes subjects with CR but incomplete recovery of blood counts (CRi). CR was assessed according to the European LeukemiaNet (ELN) guidelines, and is defined as the absence of clonal lymphocytes in the peripheral blood.	12 months
Secondary	4-week Survival Rate	"Early death" was assessed as death within 28 days of the start of treatment	28 days
Secondary	Maximum Tolerated Dose (MTD) of Lenalidomide	The maximum tolerated dose (MTD) of lenalidomide was determined in study phase 1, for use in study Phase 2 (not conducted). The outcome is reported as the dose of lenalidomide that represents the MTD.	15 months
Secondary	Remission Duration	Responses and remission were assessed according to the ELN guidelines.	26 months
Secondary	Overall Response Rate (ORR)	ORR includes subjects with CR, CRi, and partial response (PR). Responses were assessed according to the ELN guidelines.	26 months
Secondary	Overall Survival (OS)	OS from the start of treatment was assessed at a median follow up of 88 weeks from the end of treatment (range, 1-120), and was censored at 1 April 2012.	88 weeks (median)
Secondary	Time to CR	CR includes subjects with CR but incomplete recovery of blood counts (CRi). Responses were assessed according to the ELN guidelines.	18 weeks
Secondary	Time to PR	Responses were assessed according to the ELN guidelines.	36 weeks
Secondary	OS of Responders	OS from the start of treatment of responders (per ELN guidelines) was assessed at a median follow up of 88 weeks from the end of treatment (range, 1-120), and was censored at 1 April 2012.	88 weeks (median)