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A Multicentre Open Randomized Phase II Study of the Efficacy and Safety of Azacitidine Alone or in Combination With Lenalidomide in High-risk Myeloid Disease (High-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia) With a Karyotype Including Del(5q)


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Myelodysplastic Syndrome, Acute Myelogenous Leukemia

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Trial Information

A Multicentre Open Randomized Phase II Study of the Efficacy and Safety of Azacitidine Alone or in Combination With Lenalidomide in High-risk Myeloid Disease (High-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia) With a Karyotype Including Del(5q)


This is an prospective open multi-center randomized phase II study of standard dose
azacytidine with or without the addition of lenalidomide in high-risk myeloid disease
(high-risk MDS and AML) with a karyotype including del(5q). Seventy-two patients, eligible
for treatment with azacytidine (Intermedium/INT-2 and High-risk MDS and AML with 20-30 %
marrow blasts according to label) will be included.

Azacytidine will be given in a modified standard dose, azacytidine 5+2 (75 mg/m2/ d
subcutaneously for 5 days, followed by a 2-day weekend break, followed by azacytidine 75
mg/m2/ d for 2 days every 28 days, no individual dose exceeding 200 mg) for 6 cycles. Cycle
interval may be prolonged if toxicity according to predefined criteria occurs. Patients will
be randomized to azacytidine (Arm A) or azacytidine + lenalidomide (Arm B). The initial dose
of lenalidomide is 10 mg 21/28 days, starting day 1 in each azacytidine cycle and leaving
the last week before start of next azacytidine cycle free. The dose should be increased to
20 mg day 1 in cycle 4 if no toxicity according to predefined criteria occurs. The total
study period is 24 weeks + additional weeks caused by prolonged cycle interval. Patients,
who following a response may be eligible for allo-SCT may exit the study after cycle 3, 4 or
5 and then be subject to end-of-study assessment. Patients who at start of treatment, or any
time during study have a neutrophil count <0,5 x 109/l will be treated with
Granulocyte-ColonyStimulatingFactor (G-CSF).


Inclusion Criteria:



- 18 years of age at the time of signing the informed consent form.

- MDS with IPSS Int-2 or High with a karyotype including del(5q).

- Acute myeloid leukaemia (AML) with multilineage dysplasia and 20-30 % blasts (former
RAEB-t) with a karyotype including del(5q).

- Subject has signed the informed consent form.

- Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy
test prior to starting lenalidomide. In addition, sexually active WCBP must agree to
use adequate contraceptive methods (oral, injectable, patches, or implantable
hormonal contraceptive methods; tubal ligation; intra-uterine device; barrier
contraceptive with spermicide; or vasectomized partner) while on lenalidomide. WCBP
must agree to have pregnancy tests every 4 weeks while on lenalidomide.

- Males (including those who have had a vasectomy) must use barrier contraception
(latex condoms) when engaging in reproductive sexual activity with WCBP while on
lenalidomide, when temporarily stopping lenalidomide and 28 days after the last dose
of lenalidomide.

Note: Refractory and relapsed patients can be included as long as they fulfil the
inclusion criteria.

Exclusion Criteria:

- Eligible for upfront allogeneic SCT without prior induction chemotherapy or
azacitidine

- Pregnant or lactating females.

- Prior therapy with azacitidine

- Prior therapy with lenalidomide

- Expected survival less than two months.

- Acute promyelocytic leukemia (APL)

- Central nervous system leukemia

- Serum biochemical values as follows

1. Serum creatinine >2.0 mg/dL (177 mmol/L)

2. Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or
alanine transferase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x
upper limit of normal (ULN)

3. Serum total bilirubin >1.5 mg/dL

- Prior allergic reaction to thalidomide

- Uncontrolled systemic infection

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Response according to IWG criteria for MDS and AML

Outcome Description:

Response according to IWG criteria include hematologic response (including transfusion independence), bone marrow response (blast count) and cytogenetic response (karyotype) after 6 cycles of azacytidine or azacytidine+lenalidomide. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.

Outcome Time Frame:

25-44 weeks (after 6 cycles of azacitidine or azacitidine+lenalidomide)

Safety Issue:

No

Principal Investigator

Lars Möllgård, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Nordic MDS Group

Authority:

Sweden: Medical Products Agency

Study ID:

NMDSG10B

NCT ID:

NCT01556477

Start Date:

March 2012

Completion Date:

November 2014

Related Keywords:

  • Myelodysplastic Syndrome
  • Acute Myelogenous Leukemia
  • MDS
  • AML
  • Azacitidine
  • Lenalidomide
  • del5q
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

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