Azacitidine and Lenalidomide for Acute Myeloid Leukemia

NCT01016600 | Completed Phase 1 Results DMC

• 1 other identifier: 09-1816 / 201101749
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Determine toxicity and remission rates of treatment with azacitidine and lenalidomide for patients with Acute Myeloid Leukemia

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (3)

• Phase I Only - Maximum Tolerated Dose (MTD) as Measured by Dose-limiting Toxicities (DLTs)

  * The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. * Hematologic DLT is as a persistent bone marrow aplasia with ≤ 10 % cellularity, which persists for \> 60 days from the start of a chemotherapy cycle. * Non-hematologic DLT is defined as any Grade 3 or Grade 4 non-hematologic toxicity that occurs during the first cycle with the specific exceptions of nausea, vomiting, anorexia, weight loss, infections or electrolyte abnormalities attributable to any other cause. Grade 3 triglycerides will be considered a DLT only for patients who have Grade 3 in spite of appropriate lipid lowering drug therapy.

  Completion of the phase I portion of study (approximately 1 year and 4 months)

• Phase I Only - Maximum Tolerated Dose (MTD)

  * The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. * Hematologic DLT is as a persistent bone marrow aplasia with ≤ 10 % cellularity, which persists for \> 60 days from the start of a chemotherapy cycle. * Non-hematologic DLT is defined as any Grade 3 or Grade 4 non-hematologic toxicity that occurs during the first cycle with the specific exceptions of nausea, vomiting, anorexia, weight loss, infections or electrolyte abnormalities attributable to any other cause. Grade 3 triglycerides will be considered a DLT only for patients who have Grade 3 in spite of appropriate lipid lowering drug therapy.

  Completion of the phase I portion of study (approximately 1 year and 4 months)

• Phase II Only - Complete Remission Rate (CRm + CRi) in Participants With Untreated AML ≥60 Years of Age

  * Morphologic complete remission (CRm): Defined as morphologic leukemia-free state, including \<5% blasts in BM aspirate with marrow spicules and a count of \> 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC \> 1000/uL, platelet count \> 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. * Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia \<1000/uL or thrombocytopenia \<100,000/ul.

  Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)

Secondary Outcomes (12)

• Response Rate (CRm + CRc + CRi + PR)

  Median number of cycles completed [3 cycles (12 weeks) full range (1 (4 weeks)-17 (68 weeks))]

• Morphologic Leukemia-free State

  Median number of cycles completed [3 cycles (12 weeks) full range (1 (4 weeks)-17 (68 weeks))]

• Morphologic Complete Remission Rate (CRm)

  Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)

• Cytogenetic CR (CRc) Rate

  Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)

• CR With Incomplete Blood Counts Rate

  Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)

Study Arms (4)

Cohort 1

EXPERIMENTAL

Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5

Drug: Lenalidomide; Drug: Azacitidine

Cohort 2

EXPERIMENTAL

Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5

Drug: Lenalidomide; Drug: Azacitidine

Cohort 3

EXPERIMENTAL

Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5

Drug: Lenalidomide; Drug: Azacitidine

Phase II

EXPERIMENTAL

Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5

Drug: Lenalidomide; Drug: Azacitidine

Interventions

Lenalidomide DRUG

Also known as: Revlimid

Cohort 1; Cohort 2; Cohort 3; Phase II

Azacitidine DRUG

Also known as: Vidaza

Cohort 1; Cohort 2; Cohort 3; Phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed AML age ≥ 60 years, de novo, secondary to prior therapy, or transformed from MDS, as defined by the International Working Group, except acute promyelocytic leukemia (AML M3) will be included for phase 1 and 2 study. Patients must not have abnormalities of inversion 16, t(16,16), del(16q), t(8,21) or t(15,17) as assessed by routine cytogenetics or FISH. Diagnosis of AML by WHO criteria (\>20% blasts) is determined by CBC, bone marrow assessment, and immunophenotypic analysis performed within 2 weeks of study enrollment. No previous treatment for AML, however hydroxyurea, steroids, and leukopheresis are allowed.
• Relapsed AML age ≥18 years, except acute promyelocytic leukemia (AML M3), with CR \< 1 years post 1st induction chemotherapy will be included in phase 1 study only.
• Primary refractory AML age ≥18 years, except acute promyelocytic leukemia (AML M3) post 1st induction chemotherapy will be included in phase 1 study only.
• Relapsed or refractory AML age ≥18 years, except acute promyelocytic leukemia (AML M3), post 1st salvage chemotherapy/ autologous stem transplantation/ allogeneic stem cell transplantation will be included in phase 1 study only.
• Understand and voluntarily sign an informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• ECOG performance status of ≤ 2 at study entry
• Life expectancy \> 2 months
• WBC \< 10,000 x 10\^6/L (WBC counts may not be reduced by hydroxyurea or leukapheresis to achieve a WBC lower than 10,000 x 106 /L).
• Adequate renal and hepatic function as defined by:
• Serum creatinine ≤ 1.5X institution ULN
• Total bilirubin ≤ 2.0 mg/dL ( except Gilbert's syndrome or known hemolysis)
• AST(SGOT) and ALT (SGPT) ≤ 2.5 x ULN
• All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of Revlimid REMS®.
• Females of 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 prior to and again within 24 hours of starting lenalidomide 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. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.

You may not qualify if:

• Newly diagnosed AML age \< 60 years.
• Newly diagnosed AML ≥ 60 years with favorable risk cytogenetic abnormalities as defined by SWOG criteria that include: inv(16)/t(16;16)/del(16q), t(15;17) with/without secondary aberrations, t(8;21) lacking del(9q) or complex karyotype 17. Prior to enrollment, FISH studies or routine cytogenetics must be completed to rule out these cytogenetic abnormalities.
• Known CNS leukemia
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Use of any other experimental drug or therapy within 30 days of enrollment.
• Known hypersensitivity to thalidomide and mannitol.
• The development of erythema multiforme if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Any prior use of lenalidomide
• Any prior use of azacytidine.
• Concurrent use of other anti-cancer agents or treatments (with the exception of steroids)
• Known positive for HIV or infectious hepatitis, type A, B or C.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Celgene Corporation: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Lenalidomide; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Ravi Vij, M.D.
• Organization: Washington University School of Medicine

rvij@dom.wustl.edu

314-454-8304

Study Officials

• Ravi Vij, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2009
• First Posted: November 19, 2009
• Study Start: April 1, 2010
• Primary Completion: November 1, 2013
• Study Completion: October 1, 2014
• Last Updated: September 7, 2015
• Results First Posted: September 7, 2015

Record last verified: 2015-08

Locations

US (1)