Know Cancer

or
forgot password

PHASE II STUDY OF LENALIDOMIDE AND ELTROMBOPAG IN PATIENTS WITH SYMPTOMATIC ANEMIA IN LOW OR INTERMEDIATE I MYELODYSPLASTIC SYNDROME (MDS)


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Myelodysplastic Syndrome, MDS, Anemia

Thank you

Trial Information

PHASE II STUDY OF LENALIDOMIDE AND ELTROMBOPAG IN PATIENTS WITH SYMPTOMATIC ANEMIA IN LOW OR INTERMEDIATE I MYELODYSPLASTIC SYNDROME (MDS)


The rationale for this study is that combined treatment with eltrombopag (PROMACTA) and
lenalidomide (REVLIMID) will reduce the incidence of lenalidomide induced thrombocytopenia
thus enabling patients to tolerate the required duration of lenalidomide therapy leading to
higher rates of response to lenalidomide. A major reason why lenalidomide cannot be used for
the treatment of MDS is because of the occurrence of thrombocytopenia. The use of
eltrombopag will potentially raise platelet counts in these patients and enable a longer
exposure to lenalidomide. Secondly, thrombocytopenia in the first 2 months after
lenalidomide therapy predicts the subsequent response to lenalidomide treatment in patients
with low risk MDS thus raising platelet counts to enable continuation of Lenalidomide
therapy is important in these patients. Lastly, an increase in blasts has been a potential
concern with the use of thrombopoietin mimetics. Preclinical studies have indicated that
eltrombopag is less likely to increase blasts thus making it a possible potential
therapeutic candidate in low risk MDS.


Inclusion Criteria:



1. Age ≥ 18 years.

2. Patient must have a documented diagnosis of MDS of at least three months duration
(MDS duration ≥ 3 months) according to World Health Organization (WHO) criteria (see
Appendix IV) or non-proliferative chronic myelomonocytic leukemia (CMML) (WBC ≤
12,000/L)).

3. Patients must have International Prognostic Scoring System (IPSS) categories of Low-
or Intermediate-1-risk disease (see Section 6).

4. Patients must have symptomatic anemia untransfused with hemoglobin ≤ 9.5 g/dL within
8 weeks of registration or with red blood cell (RBC) transfusion-dependence (i.e., ≥
2 units/month) confirmed for a minimum of 8 weeks before randomization.

5. Patients must have IPSS score determined by cytogenetic analysis prior to
randomization. Patients with cytogenetic failure and ≤ 10% marrow blasts will be
eligible.

6. Patients must be off all disease modifying therapy for MDS for 28 days prior to
initiation of study treatment. Patients may receive hydrocortisone prophylactically
to prevent transfusion reactions.

7. Patients must not have documented iron deficiency. All patients must have documented
marrow iron stores. If marrow iron stain is not available, the transferrin saturation
must be ≥ 20% or a serum ferritin ≥ 100 mg/100 mL or soluble transferring receptor <
5mg/L.

8. Women must not be pregnant or breastfeeding. Females of childbearing potential should
have 2 negative pregnancy tests. The first test should be performed within 10-14
days, and the second test within 24 hours prior to prescribing lenalidomide.

9. Women of childbearing potential and sexually active males must agree to use 2 methods
of an accepted and effective method of contraception and counseled on the potential
teratogenic effects of lenalidomide. Effective contraception must be used by patients
for at least 4 weeks before beginning lenalidomide therapy, during lenalidomide
therapy, during dose interruptions and for 4 weeks following discontinuation of
lenalidomide therapy. Reliable contraception is indicated even where there has been a
history of infertility, unless due to hysterectomy or because the patient has been
postmenopausal naturally for at least 24 consecutive months. Two reliable forms of
contraception must be used simultaneously unless continuous abstinence from
heterosexual sexual contact is the chosen method. Females of childbearing potential
should be referred to a qualified provider of contraceptive methods, if needed.
Sexually mature females who have not undergone a hysterectomy or who have not been
postmenopausal naturally for at least 24 consecutive months (i.e., who have had
menses at some time in the preceding 24 consecutive months) are considered to be
females of childbearing potential. It is not known whether CC-5013 (lenalidomide) is
present in the semen of patients receiving the drug. Therefore, males receiving
CC-5013 (lenalidomide) must always use a latex condom during any sexual contact with
females of childbearing potential even if they have undergone a successful vasectomy.

10. Patients must not have received prior therapy with lenalidomide (for more than 2
months) nor eltrombopag.

11. Patients must not have uncontrolled hypertension.

12. Patients must have absolute neutrophil count (ANC) ≥500 cells/L (0.5 x 109/L).

13. ECOG Performance 0-3 (ECOG).

14. Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must be
within 80 to 120% of the normal range at baseline.

15. Patient is able to understand protocol requirements.

Exclusion Criteria:

1. Pre-existing cardiovascular disease (including congestive heart failure, New York
Heart Association (NYHA) Grade III/IV), or arrhythmia known to increase the risk of
thromboembolic events (e.g. atrial fibrillation), or subjects with a corrected QT
interval (QTc) >450 msec.

2. Patients determined to be at increased risk of arterial or venous thrombosis by the
investigator

3. Bone marrow fibrosis that leads to a dry tap.

4. Female subjects who are nursing or pregnant (positive serum or urine -human chorionic
gonadotropin (-hCG) pregnancy test) at screening or pre-dose on Day 1.

5. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
longer) preceding the first dose of study medication.

6. Patients with documented liver cirrhosis

7. Patients with splenomegaly with a spleen size > 16cm.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Hematologic improvement

Outcome Description:

To evaluate the rate of hematologic improvement of the eltrombopag/lenalidomide combination as defined by the International Working Group (IWG) criteria

Outcome Time Frame:

2 years

Safety Issue:

No

Principal Investigator

Amit Verma, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Montefiore Medical Center-Weiler Division

Authority:

United States: Food and Drug Administration

Study ID:

2012-407

NCT ID:

NCT01772420

Start Date:

October 2012

Completion Date:

October 2016

Related Keywords:

  • Myelodysplastic Syndrome
  • MDS
  • Anemia
  • Myelodysplastic Syndrome
  • MDS
  • Anemia
  • Eltrombopag
  • Lenalidomide
  • Bone Marrow Diseases
  • Hematologic Diseases
  • Precancerous Conditions
  • Preleukemia
  • Anemia
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Montefiore Medical Center-Department of Medical OncologyBronx, New York  10461