Safety, Efficacy, & Pharmacokinetic Study of Tamibarotene to Treat Patients With Relapsed or Refractory APL

Related Clinical Trial
A Study of CG-806 in Patients With Relapsed or Refractory Acute Myeloid Leukemia Total Marrow Irradiation for Refractory Acute Leukemia Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia Therapeutic Allogeneic Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant MEK Inhibitor MEK162, Idarubicin, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Organ-Sparing Marrow-Targeted Irradiation Before Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS) Radiolabeled BC8 Antibody, Busulfan, Cyclophosphamide Followed by Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia in First Remission 3-AP and High-Dose Cytarabine in Treating Patients With Advanced Hematologic Malignancies Busulfan and Etoposide Followed by Peripheral Blood Stem Cell Transplant and Low-Dose Aldesleukin in Treating Patients With Acute Myeloid Leukemia Vaccine Therapy and Basiliximab in Treating Patients With Acute Myeloid Leukemia in Complete Remission Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia PXD101 in Treating Patients With Acute Myeloid Leukemia Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies Lenalidomide and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Bendamustine and Idarubicin in Treating Older Patients With Previously Untreated AML or MDS Clofarabine and Cytarabine in Treating Patients With Acute Myeloid Leukemia With Minimal Residual Disease Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Selinexor and Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Decitabine and Bortezomib in Treating Patients With Acute Myeloid Leukemia Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome SJG-136 in Treating Patients With Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndromes, Blastic Phase Chronic Myelogenous Leukemia, or Chronic Lymphocytic Leukemia Daunorubicin Hydrochloride, Cytarabine and Oblimersen Sodium in Treating Patients With Previously Untreated Acute Myeloid Leukemia GTI-2040 and High-Dose Cytarabine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia Connect® MDS/AML Disease Registry Combined PD1 Inhibitor and Decitabine in Elderly Patients With Relapse and Refractory Acute Myeloid Leukemia Vorinostat in Treating Patients With Acute Myeloid Leukemia Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Romidepsin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia Economic Analysis of Blood Product Transfusions According to the Treatment of Acute Myeloid Leukaemia in the Elderly Comparison of Diagnostic Yield Among M-FISH, FISH Probe Panel and Conventional Cytogenetic Analysis in AML Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia Bortezomib in Treating Young Patients With Refractory or Recurrent Leukemia Red Cell Transfusion Goals in Patients With Acute Leukemias A PALG Prospective Multicenter Clinical Trial to Compare the Efficacy of Two Standard Induction Therapies (DA-90 vs DAC) and Two Standard Salvage Regimens (FLAG-IDA vs CLAG-M) in AML Patients ≤ 60 Years Old An Efficacy and Safety Study Of Pracinostat In Combination With Azacitidine In Adults With Acute Myeloid Leukemia Fludarabine and Cytarabine as Continuous Infusion Plus G-CSF Priming for Elderly Patients With Resistant AML Phase I/II Trial of ATRA and TCP in Patients With Relapsed or Refractory AML and no Intensive Treatment is Possible Prognostic Values of Next Generation Sequencing (NGS) in Acute Myeloid Leukemia Patients With Allo-HSCT PET/MRI, 18F-FDG PET/CT and Whole Body MRI in Finding Extramedullary Myeloid Leukemia in Patients With Newly Diagnosed Acute Myeloid Leukemia Pilot Clinical Trial of Pazopanib in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or at Initial Diagnosis When no Intensive Treatment is Possible A Safety Study of SGN-CD33A in AML Patients FLAG+Ida With G-CSF Priming for Patients Younger Than 60 Years With Resistant AML Study on Number and Outcome of Pregnancy in Acute Promielocitic Leukaemia (APL) Patients Treated With Chemotherapy Biomarkers in Bone Marrow Samples From Patients With Acute Promyelocytic Leukemia Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia A Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia ASCT for Relapsed APL After Molecular Remission Diagnostic Study of Patients With Acute Lymphoblastic Leukemia or Acute Promyelocytic Leukemia National Acute Promyelocytic Leukemia (APL) Observational Study NAPOLEON-Registry of the German AML Intergroup All-trans Retinoic Acid, and Arsenic +/- Idarubicin Safety, Efficacy, & Pharmacokinetic Study of Tamibarotene to Treat Patients With Relapsed or Refractory APL Randomized,International Multi-center Clinical Trial of RIF Plus RA for Non-high-risk APL Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia AIDA 2000 Guidelines Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia The Acute Promyelocytic Leukaemia Asian Consortium (APL-AC) Project Combined Retinoic Acid,Arsenic Trioxide and Chemo for Newly-diagnosed APL French Registry of First-line Treatment of Acute Promyelocytic Leukemia New Retinoid Agent Combined With Arsenic Trioxide for Untreated Acute Promyelocytic Leukemia Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Promyelocytic Leukemia Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO) Treatment of Newly Diagnosed Patients With Acute Promyelocytic Leukemia (PETHEMA LPA 2005) Long-Term Quality of Life in Patients With Acute Promyelocytic Leukemia Tamibarotene and Arsenic Trioxide for Relapsed Acute Promyelocytic Leukemia Long-term QoL in Acute Promyelocytic Leukemia Treated With ATO or Standard Chemotherapy Treatment of Non-high-risk Acute Promyelocytic Leukemia (APL) With Realgar-Indigo Naturalis Formula (RIF) Treatment of Acute Promyelocytic Leukemia With All-Trans Retinoic Acid (ATRA) and Idarubicin (AIDA) Single Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia Study for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia Treatment Protocol for Relapsed Acute Promyelocytic Leukemia (APL) With Arsenic Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia Role of Microparticles in the Coagulopathy of Acute Promyelocytic Leukemia Proteasome Inhibition in Acute Promyelocytic Leukemia

Brief Title

Safety, Efficacy, & Pharmacokinetic Study of Tamibarotene to Treat Patients With Relapsed or Refractory APL

Official Title

A Phase II Study of Oral Tamibarotene in Acute Promyelocytic Leukemia Patients Who Have Received Prior Therapy With ATRA and Arsenic Trioxide (STAR-1)

Brief Summary

      This is a Phase II, open-label, non-randomized study to evaluate the safety, efficacy, and
      pharmacokinetics of tamibarotene in adult patients with relapsed or refractory acute
      promyelocytic leukemia (APL) following treatment with all-trans-retinoic acid (ATRA) and
      arsenic trioxide (ATO). Patients must have received and failed therapy with ATRA and ATO.
      Treatment may have been administered either as combination therapy or sequentially as single
      agents. Patients who are intolerant to either drug are eligible for this study.
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

To determine the rate of durable complete response for tamibarotene therapy when administered as a single agent to adult patients with relapsed or refractory APL.

Secondary Outcome

 (1) To determine the rates of morphologic leukemia-free state, partial response, cytogenetic complete response, and molecular complete response for tamibarotene therapy in the indicated patient population.

Condition

Acute Promyelocytic Leukemia

Intervention

Tamibarotene


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

15

Start Date

September 2007

Completion Date

January 2013

Primary Completion Date

December 2012

Eligibility Criteria

        Patients must meet all of the following criteria for admission into the study:

          1. Have a diagnosis of either relapsed and/or refractory APL:

               -  Refractory disease is defined as a confirmed diagnosis of APL and a myeloblast
                  plus promyelocyte count of > 10% in the bone marrow in patients who have failed
                  to respond to induction therapy in the first or second line setting. Induction
                  therapy must have included ATRA- and ATO-based therapy given either sequentially
                  or in combination.

               -  Relapsed disease is defined as a confirmed diagnosis of APL and a myeloblast plus
                  promyelocyte count of > 10% in the bone marrow following a documented complete
                  remission or positive RT-PCR assay for PML/RAR-α in two consecutive tests
                  separated by at least one month, after treatment with ATRA- and ATO-based therapy
                  given either sequentially or in combination.

          2. Confirmation of diagnosis and relapsed/refractory APL must be obtained in blood or
             bone marrow mononuclear cells by at least one of the following methods:

               -  Conventional cytogenetics showing the translocation t(15:17),

               -  Positive RT-PCR assay for PML/RAR-α, or

               -  Fluorescence in situ hybridization (FISH) analysis showing evidence of the
                  PML/RAR-α translocation.

          3. Patients must have received and failed therapy with ATRA and ATO either within the
             same or separate induction/consolidation schedule(s). Treatment must have been
             administered for a minimum of 28 days for each agent. Treatment may have been
             administered either as combination therapy or sequentially as single agents. Patients
             who failed to complete a course of induction/consolidation therapy, as specified, due
             to drug intolerance are eligible for the study.

          4. Patients in whom ATO is contraindicated (for example due to congenital long QT
             syndrome) are eligible for inclusion on study if they have received and failed ATRA
             therapy as defined in (3).

          5. Be able to provide written informed consent prior to enrollment into the study.

          6. Be ≥ 18 years old.

          7. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

          8. Have an estimated life expectancy of ≥ 12 weeks.

          9. Be male or a non-pregnant, non-lactating female. Fertile patients must agree to use an
             effective barrier method of contraception (e.g., latex condom, diaphragm, or cervical
             cap) to avoid pregnancy while on therapy and for 90 days following the discontinuation
             of the study drug. [In countries where double barrier contraception is required by
             Regulatory Authorities, patients who are fertile must agree to use 2 forms of barrier
             method contraception (e.g., latex condom AND a diaphragm or cervical cap) while on
             therapy and for 90 days following the discontinuation of the study drug.]

             A non-fertile female is defined as:

               -  Postmenopausal (amenorrheic for ≥ 12 months)

               -  Undergone a complete oophorectomy or hysterectomy.

         10. Have a negative serum or urine pregnancy test within 10 days prior to the first dose
             of study drug (if patient is a female of childbearing potential).

         11. Have adequate organ function.

        Patients who meet any of the following criteria will be excluded from study admission:

          1. Extramedullary leukemia.

          2. Patients on a vitamin A preparation or patients with hypervitaminosis A.

          3. Have received cytotoxic therapy ≤ 2 weeks from the start of therapy. If the patient
             needs these agents due to urgent medical care within 2 weeks prior to starting
             tamibarotene, a waiver may be granted by the INNOVIVE Medical Monitor.

          4. Have a history of myelodysplastic syndromes (MDS).

          5. Have impaired cardiac function or clinically significant heart disease including:

               -  Myocardial infarction within 3 months, unstable angina pectoris, congenital long
                  QT syndrome and clinically significant resting bradycardia (< 50 beats per
                  minute), uncontrolled congestive heart failure, uncontrolled hypertension,
                  history of labile hypertension, or history of poor compliance with
                  antihypertensive medication.

          6. Have an active, uncontrolled systemic infection considered opportunistic,
             life-threatening, or clinically significant at the time of treatment.

          7. Have clinically significant acute or chronic liver or renal disease considered
             unrelated to leukemia.

          8. Have uncontrolled hyperlipidemia.

          9. Have uncontrolled or poorly controlled diabetes mellitus.

         10. Have impaired gastrointestinal function that may significantly alter drug absorption
             (e.g., uncontrolled vomiting, ulcerative colitis, malabsorption, or small bowel
             resection).

         11. Are pregnant or lactating.

         12. Have psychiatric disorder(s) that would interfere with consent, study participation,
             or follow-up.

         13. Have not recovered from acute toxicities of all previous therapy prior to enrollment.

         14. Have any other severe concurrent disease and/or uncontrolled medical conditions,
             which, in the judgment of the investigator, could predispose patients to unacceptable
             safety risks or compromise compliance with the protocol.

         15. Have a history of another primary malignancy that has been actively treated in the
             last 24 months.

         16. Are unwilling or unable to comply with the protocol.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jorge Cortes, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00520208

Organization ID

INNO-507-P2


Responsible Party

Sponsor

Study Sponsor

CytRx


Study Sponsor

Jorge Cortes, MD, Principal Investigator, M.D. Anderson Cancer Center


Verification Date

February 2013