Adult Acute Megakaryoblastic Leukemia (M7)Phase 1NCT01904643

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

A Phase 1 study testing lenalidomide, mitoxantrone hydrochloride and etoposide in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by Stanford University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a)
What is being tested?: lenalidomide, mitoxantrone hydrochloride and etoposide
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 1 siteUnited States
Study dates: Feb 2014to 18 Jul 2015
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Stanford University, School of Medicine
Stanford, California, 94305

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About this study

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)

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.

Read the 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).

II. 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.

Conditions: 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)
Being tested: lenalidomide, mitoxantrone hydrochloride, etoposide, cytarabine
Medical subject headings: Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

lenalidomideDrug
Also called CC-5013, IMiD-1, Revlimid
Given PO
mitoxantrone hydrochlorideDrug
Also called CL 232315, DHAD, DHAQ, Novantrone
Given IV
etoposideDrug
Also called EPEG, VP-16, VP-16-213
Given IV
cytarabineDrug
Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U
Given IV

Study groups in NCT01904643
Study group	Role	What they receive
Treatment (lenalidomide, combination chemotherapy)	Experimental	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. Receives: Drug: lenalidomide; Drug: mitoxantrone hydrochloride; Drug: etoposide; Drug: cytarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Hematologic and non-hematologic toxicities will be tabulated.
Measured: 42 days

Secondary outcomes (3)

Response rate (complete remission [CR], CR with incomplete blood count recovery [CRi], partial remission [PR] or stable disease [SD]) using LeukemiaNet guidelines
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.
Measured: Up to 6 months
Response duration
Summarized using a Kaplan-Meier plot.
Measured: From start of induction, assessed up to 6 months
Early mortality
Summarized using a Kaplan-Meier plot.
Measured: From start of induction, assessed up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 201418 Jul 2015

First posted22 Jul 2013 (estimated)
Study startFeb 2014
Primary completion13 May 2015
Study completion18 Jul 2015

Why it stopped: Accrual factor

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Adult Acute Megakaryoblastic Leukemia (M7)Studies of the same condition, open and under way.
More trials run by Stanford UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01904643
Sponsor's protocol ID: IRB-27313
Other IDs: NCI-2013-01349, IRB-27313, P30CA124435, HEMAML0024
Status last verified: Oct 2018
First submitted: 17 Jul 2013
Last updated: 29 Oct 2018
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No