Lenalidomide and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Sponsor

Stanford University (Other)

Overall Status

Terminated

CT.gov ID

NCT01904643

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

17.5

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I trial studies the side effects and the best dose of lenalidomide when given together with combination chemotherapy in treating patients with relapsed or refractory acute myeloid leukemia. Lenalidomide may stop the growth of acute myeloid leukemia by blocking blood flow to the cancer. Drugs used in chemotherapy, such as mitoxantrone hydrochloride, etoposide, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide and combination chemotherapy may be an effective treatment for acute myeloid leukemia.

Condition or Disease	Intervention/Treatment	Phase
Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Minimally Differentiated Myeloid Leukemia (M0) Adult Acute Monoblastic Leukemia (M5a) Adult Acute Monocytic Leukemia (M5b) Adult Acute Myeloblastic Leukemia With Maturation (M2) Adult Acute Myeloblastic Leukemia Without Maturation (M1) Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Acute Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Recurrent Adult Acute Myeloid Leukemia	Drug: lenalidomide Drug: mitoxantrone hydrochloride Drug: etoposide Drug: cytarabine	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

To determine the maximum tolerated dose (MTD) of lenalidomide when used in combination with mitoxantrone hydrochloride, etoposide, and cytarabine (MEC) in patients with relapsed or refractory acute myeloid leukemia (AML).
To determine the dose-limiting toxicities (DLTs) of this combination in this patient population.

SECONDARY OBJECTIVES:

To determine whether the combination of lenalidomide priming prior to re-induction chemotherapy with MEC has clinical activity in patients with relapsed or refractory AML.

OUTLINE: This is a dose-escalation study of lenalidomide.

LENALIDOMIDE PRIMING: Patients receive lenalidomide orally (PO) for 5 or 7 days.

RE-INDUCTION CHEMOTHERAPY: Patients receive etoposide intravenously (IV) over 1 hour, cytarabine IV over 3 hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-5. Patients failing to achieve blast count < 5% at 21 days may receive a second course of induction therapy. Patients achieving complete remission proceed to lenalidomide priming.

LENALIDOMIDE PRIMING: Within 4-6 weeks, patients receive lenalidomide PO for 5 or 7 days and then proceed to consolidation therapy.

CONSOLIDATION CHEMOTHERAPY: Patients receive etoposide IV over 1 hour, cytarabine IV over 3 hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-4. Treatment repeats every 28-35 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 6 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

17 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of Lenalidomide Therapy Prior to Re-induction Chemotherapy With Mitoxantrone, Etoposide, and Cytarabine (MEC) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (AML)

Study Start Date :

Feb 1, 2014

Actual Primary Completion Date :

May 13, 2015

Actual Study Completion Date :

Jul 18, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (lenalidomide, combination chemotherapy) LENALIDOMIDE PRIMING: Patients receive lenalidomide PO for 5 or 7 days. RE-INDUCTION CHEMOTHERAPY: Patients receive etoposide IV over 1 hour, cytarabine IV over 3 hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-5. Patients failing to achieve blast count < 5% at 21 days may receive a second course of induction therapy. Patients achieving complete remission proceed to lenalidomide priming. LENALIDOMIDE PRIMING: Within 4-6 weeks, patients receive lenalidomide PO for 5 or 7 days and then proceed to consolidation therapy. CONSOLIDATION CHEMOTHERAPY: Patients receive etoposide IV over 1 hour, cytarabine IV over 3 hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-4. Treatment repeats every 28-35 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.	Drug: lenalidomide Given PO Other Names: CC-5013 IMiD-1 Revlimid Drug: mitoxantrone hydrochloride Given IV Other Names: CL 232315 DHAD DHAQ Novantrone Drug: etoposide Given IV Other Names: EPEG VP-16 VP-16-213 Drug: cytarabine Given IV Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside

Arm

Intervention/Treatment

Experimental: Treatment (lenalidomide, combination chemotherapy)

LENALIDOMIDE PRIMING: Patients receive lenalidomide PO for 5 or 7 days. RE-INDUCTION CHEMOTHERAPY: Patients receive etoposide IV over 1 hour, cytarabine IV over 3 hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-5. Patients failing to achieve blast count < 5% at 21 days may receive a second course of induction therapy. Patients achieving complete remission proceed to lenalidomide priming. LENALIDOMIDE PRIMING: Within 4-6 weeks, patients receive lenalidomide PO for 5 or 7 days and then proceed to consolidation therapy. CONSOLIDATION CHEMOTHERAPY: Patients receive etoposide IV over 1 hour, cytarabine IV over 3 hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-4. Treatment repeats every 28-35 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Drug: lenalidomide

Given PO

Other Names:

CC-5013

IMiD-1

Revlimid

Drug: mitoxantrone hydrochloride

Given IV

Other Names:

CL 232315

DHAD

DHAQ

Novantrone

Drug: etoposide

Given IV

Other Names:

EPEG

VP-16

VP-16-213

Drug: cytarabine

Given IV

Other Names:

ARA-C

arabinofuranosylcytosine

arabinosylcytosine

Cytosar-U

cytosine arabinoside

Outcome Measures

Primary Outcome Measures

MTD of lenalidomide when used in combination with MEC determined by DLT using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 [42 days]
Hematologic and non-hematologic toxicities will be tabulated.

Secondary Outcome Measures

Response rate (complete remission [CR], CR with incomplete blood count recovery [CRi], partial remission [PR] or stable disease [SD]) using LeukemiaNet guidelines [Up to 6 months]
Proportions of these patients in each response category will be tabulated; the combined proportion in categories CR, CRi, PR, and SD will be computed along with an exact 95% confidence interval.
Response duration [From start of induction, assessed up to 6 months]
Summarized using a Kaplan-Meier plot.
Early mortality [From start of induction, assessed up to 6 months]
Summarized using a Kaplan-Meier plot.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients eligible include those with diagnosis of AML other than acute promyelocytic leukemia by World Health Organization (WHO) criteria with relapsed disease after induction therapy or refractory to induction chemotherapy, as determined by morphology on bone marrow biopsy; also eligible are patients unwilling to receive standard induction chemotherapy
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Serum creatinine =< 1.5 mg/dL; if serum creatinine > 1.5 mg/dL, then the estimated glomerular filtrate rate (GFR) must be > 60ml/min/1.73m^2 as calculated by the Modification of Diet in Renal Disease equation
Serum bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is considered to be secondary to Gilbert's syndrome, hemolysis, or hepatic infiltration by AML
Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 x ULN
Alkaline phosphatase =< 2.5 x ULN
All study participants must be registered into the mandatory Revlimid assistance (RevAssist) program, and be willing and able to comply with the requirements of RevAssist
Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for cycle 1 (prescriptions must be filled within 7 days as required by RevAssist) and must either commit to 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 she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy

Exclusion Criteria:

Patient must not undergo concomitant radiotherapy, chemotherapy or immunotherapy; patient must not be in concurrent study with other investigational agents
Patients who have received prior lenalidomide therapy are not eligible for this study; further there should be at least a 14-day window from the patient's last prior therapy before initiation of treatment on clinical trial
Have other severe concurrent disease or serious organ dysfunction involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatment
Have significant, uncontrolled active infection
Pregnant or nursing patients will be excluded from the study
Known human immunodeficiency virus (HIV) infection