Pomalidomide After Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

NCT02029950 | Completed Phase 1

• 8 other identifiers: NCI-2013-02426J13128NA_000897399524P30CA006973U01CA070095UM1CA186691UM1CA186704
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects and best dose of pomalidomide after combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as cytarabine, daunorubicin hydrochloride, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Pomalidomide may kill cancer cells by stopping blood flow to the cancer and by stimulating white blood cells to kill cancer cells. Giving more than one drug (combination chemotherapy) and pomalidomide may kill more cancer cells.

Conditions

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia-2; High Risk Myelodysplastic Syndrome; Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of pomalidomide, defined as the highest dose at which 0 or 1 dose-limiting toxicities are observed in 6 patients by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (5.0 beginning April 1, 2018)

  The proportion of dose-limiting toxicities at each dose level will be reported with exact binomial 95% confidence intervals. Adverse events will be summarized by dose level for all doses. All toxicities by type and grade will be reported.

  Up to 21 days

Secondary Outcomes (4)

• Proportion of toxicities in the expansion cohort graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (5.0 beginning April 1, 2018)

  Up to 2 years

• Proportion of patients achieving complete remission, complete remission with incomplete count recovery, or partial remission

  Up to 2 years

• Progression-free survival

  Time from start of treatment to time of progression or relapse or death, assessed up to 2 years

• Overall survival

  Time of enrollment onto this study to the time of death, assessed up to 2 years

Other Outcomes (4)

• Change in lymphocyte subpopulations

  Baseline to up to 1 year

• Change in levels of antigen-specific CD8+ T cell responses

  Baseline to up to 1 year

• Presence of minimal residual disease-leukemic stem cells in marrow

  Day 14

Study Arms (1)

Treatment (combination chemotherapy, pomalidomide)

EXPERIMENTAL

See Detailed Description

Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Etoposide; Drug: Idarubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Pomalidomide

Interventions

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (combination chemotherapy, pomalidomide)

Daunorubicin Hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin Hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilem

Treatment (combination chemotherapy, pomalidomide)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16

Treatment (combination chemotherapy, pomalidomide)

Idarubicin Hydrochloride DRUG

Given IV

Also known as: Idamycin, Idamycin PFS, Idarubicin HCl, IMI-30, SC-33428, Zavedos

Treatment (combination chemotherapy, pomalidomide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (combination chemotherapy, pomalidomide)

Pharmacological Study OTHER

Correlative studies

Treatment (combination chemotherapy, pomalidomide)

Pomalidomide DRUG

Given PO

Also known as: 4-Aminothalidomide, Actimid, CC-4047, Imnovid, Pomalyst

Treatment (combination chemotherapy, pomalidomide)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed:
• Pathologically confirmed intermediate or poor risk newly diagnosed AML (subtypes M0, 1, 2, 4-7), but excluding newly diagnosed core-binding factor (CBF) (t(8;21) or M4eo subtype (inv(16) or t(16;16) AMLs and acute promyelocytic leukemia (acute promyelocytic leukemia \[APL\], M3)
• MDS with high risk features as defined by intermediate (INT)-2 or high International Prognostic Scoring System (IPSS) score with \> 10% blasts in the bone marrow
• Chronic myelomonocytic leukemia-2 (CMML-2) defined as having \> 10% blasts (including promonocytes) in the bone marrow or 5-19% blasts (including promonocytes) in the peripheral blood
• Patients who have received hydroxyurea alone or have received non-cytotoxic therapies previously for treatment of MDS or myeloproliferative neoplasm (MPN) (e.g. azacitidine, decitabine, histone deacetylase inhibitors, tyrosine kinase inhibitors, hematopoietic growth factors, interferon, lenalidomide, thalidomide) will be eligible for this trial as long as immunomodulatory drugs (e.g. lenalidomide, thalidomide) have not been used in the past 3 months
• Patients must be off all non-cytotoxic chemotherapies or biologic agents (e.g. azacitidine, decitabine, histone deacetylase inhibitors, tyrosine kinase inhibitors, hematopoietic growth factors, interferon, but excluding hydroxyurea and cyclophosphamide) for at least 2 weeks prior to starting induction chemotherapy
• Patients must be off radiation therapy or chemotherapy 4 weeks (6 weeks for nitrosoureas or mitomycin C) of starting induction chemotherapy
• All adverse events (excluding alopecia, acne, rash) due to agents administered more than 2 weeks earlier should recover to =\< grade 1; patients with hematologic malignancies are expected to have hematologic abnormalities at study entry; these abnormalities which are thought to be primarily related to the underlying leukemia, are not considered to be toxicities (adverse events \[AE\]) and do not need to resolve to =\< grade 1
• Patients with therapy-related AML or MDS should have not received prior cumulative anthracycline (daunorubicin equivalent) lifetime dose \> 450 mg/m\^2
• Cytoreduction allowed:
• Hydroxyurea, corticosteroids, leukapheresis can be used prior to start of induction chemotherapy
• Cyclophosphamide up to dose 50-60 mg/kg is allowed for cytoreduction, but must be given at least 7+/- 2 days before start of induction chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 50%)
• Total bilirubin \< 2.0 mg/dL unless due to Gilbert's disease, hemolysis or leukemia
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional upper limit of normal unless due to leukemic infiltration

You may not qualify if:

• Patients who are receiving any other investigational agents or who have received pomalidomide in the past
• Patients with known active central nervous system leukemia should be excluded from this clinical trial; patient receiving intrathecal chemotherapy prophylaxis should not receive pomalidomide for \>= 3 days after administration
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pomalidomide (e.g. lenalidomide, thalidomide) or other agents used in study
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide or similar drugs in the past
• Uncontrolled intercurrent illness including, but not limited to, active and uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, mental deficits, psychiatric illness or history or social situations that would limit compliance with study requirements; patients with infection under active treatment and controlled with antibiotics are eligible
• Any other medical condition that in opinion of investigator would place patient at increased risk for toxicity during pomalidomide treatment (i.e. history of recurrent or serious thromboembolic events)
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with pomalidomide
• Known positive patients for infectious hepatitis, type A, B, C
• Active graft-versus-host disease (GVHD) following allogeneic stem cell transplant for non-AML condition (ex. MDS, MPN, lymphoid malignancy, aplastic anemia) requiring ongoing use of immunosuppressants

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Yale University

New Haven, Connecticut, 06520, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myeloproliferative Disorders

Interventions

Cytarabine; Daunorubicin; Etoposide; Idarubicin; 4-demethoxydaunorubicin bis(hydrazone); pomalidomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Study Officials

• Ivana Gojo

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2014
• First Posted: January 8, 2014
• Study Start: December 16, 2013
• Primary Completion: May 13, 2020
• Study Completion: May 13, 2020
• Last Updated: October 14, 2020

Record last verified: 2020-10

Locations

US (3)