Neoplasms

Blood and Lymph Conditions

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Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Patients receive an allogenic stem cell transplantation from an HLA-matched unrelated or related donor

Patients receive a standard chemotherapy as consolidation therapy

Human Stem Cell Transplantation

Consolidation chemotherapy, recommended regimen: HiDAC = 3 x 2g/sqm BID on days 1,3,5

Consolidation chemotherapy, i.e. High-dose Cytarabine (HiDAC)

Martin Bornhaeuser, Prof. (MD)

Hematopoietic stem cell transplantation in patients with newly diagnosed AML ≤60 years of age in intermediate risk, after first complete response in comparison to standard consolidation chemotherapy

Haematopoietic Stem Cell Transplantation (HSCT) in Comparison to Conventional Consolidation Therapy for Patients With Acute Myeloid Leukemia (AML) (Intermediate Risk) </= 60y. After First CR

Randomised Trial on Allogeneic Haematopoietic Stem Cell Transplantation in Patients Under the Age of 60 Years With Acute Myeloid Leukemia of Intermediate Risk in First Complete Remission and a Matched Sibling or Unrelated Donor (ETAL-1)

The status of each patient alive/not alive is surveyed every 3 months in year 1+2 and every 6 months in year 3+4 after randomisation.

Scores assessed by validated questionnaires (8 subscales: physical function, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health)

German Research Foundation

University Hospital Carl Gustav Carus

Antibodies

Antibodies, Monoclonal

Daunorubicin

Immunoglobulins

Gemtuzumab

Calicheamicins

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

INDUCTION: Patients receive liposome-encapsulated daunorubicin 44mg/m2 - cytarabine 100mg/m2 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin 3 mg/m2 (max 4.5 mg) IV over 120 minutes on day 7, or days 4 and 7, or days 1, 4, and 7 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients who achieve CR/CRi receive consolidation therapy at the discretion of the treating physician and/or proceed to allogeneic HSCT.

Gemtuzumab Ozogamicin

Liposome-encapsulated Daunorubicin-Cytarabine

Caspian Oliai, MD

This phase Ib trial studies the best dose of gemtuzumab ozogamicin when given together with CPX-351 in treating patients with acute myeloid leukemia that has come back after it was previously in remission. CPX-351 is a chemotherapy, which works 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. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to chemotherapy called calicheamicin. Gemtuzumab attaches to CD33 (transmembrane receptor) positive cancer cells in a targeted way and delivers ozogamicin to kill them. Giving CPX-351 and gemtuzumab ozogamicin may work better in treating patients with acute myeloid leukemia, compared to giving only one of these therapies alone.

PRIMARY OBJECTIVES:

I. To determine the phase II dose of the combination liposome-encapsulated daunorubicin-cytarabine (CPX-351) plus gemtuzumab ozogamicin (GO) by means of estimating maximum tolerated dose (MTD) in participants with relapsed acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

I. To estimate the remission rate (complete remission plus complete remission with incomplete hematologic recovery) of participants in the MTD cohort who receive CPX-351 plus GO.

II. To evaluate CPX-351 plus GO as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT) in participants with relapsed AML.

III. To estimate the duration of remission. IV. To evaluate for toxicity by means of Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

V. To evaluate for the development of veno-occlusive disease at any point during the study in participants treated with CPX-351 plus GO.

VI. To evaluate time to return of normal hematopoiesis after induction therapy. VII. To evaluate 30- and 60-day survival.

EXPLORATORY OBJECTIVES:

I. To evaluate if there is a difference in remission rate based on CD33 splicing single nucleotide polymorphism (SNP) genotype (CC, TC, or TT) in participants receiving CPX-351 plus GO.

II. To evaluate the impact that leukemia cell multidrug resistance activity have on achieving remission after treatment with CPX-351 plus GO.

III. To evaluate the possible associations of participant constitutional genotype, leukemia genotype, and response to therapy.

IV. To evaluate the possible associations of participant ribonucleic acid (RNA) expression, leukemia RNA expression, and response to therapy.

OUTLINE: This is a dose-escalation study of gemtuzumab ozogamicin when given in combination with liposome-encapsulated daunorubicin-cytarabine.

INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 7 in the first cohort of study participants, days 4 and 7 in the second cohort of study participants, or days 1, 4, and 7 in the third cohort of study participants, in the absence of disease progression or unacceptable toxicity. The dose expansion cohort will receive the above treatment schedule that is determined to be the maximum tolerated dose.

CONSOLIDATION: Patients who achieve complete remission (CR)/CR with incomplete hematologic recovery (CRi) receive consolidation therapy at the discretion of the treating physician and/or proceed to allogeneic HSCT.

CPX-351 and Gemtuzumab Ozogamicin in Treating Patients With Relapsed Acute Myeloid Leukemia

A Phase Ib Trial With Dose Expansion Evaluating CPX-351 Plus Gemtuzumab Ozogamicin for Relapsed Acute Myelogenous Leukemia

Determined by whole exome sequencing and confirmatory genotyping.

Will be determined by the flow cytometry mean fluorescence intensity (MFI) of the efflux of the fluorescent dye DiOC2 (Diethyloxacarbocyanine iodide) (by malignant cells. Will be assessed by dye efflux assay as described by Walter et al. 2003.

Will be determined by the flow cytometry efflux MFI of the efflux of the fluorescent dye 5-carboxy-2?,7?-dichlorofluorescein diacetate (CDCF) by malignant cells. Will be assessed by dye efflux assay as described by Walter et al. 2003.

Tumor deoxyribonucleic acid (DNA) and participant DNA will be measured via Illumina HiSeq3000 sequencing platform to evaluate for associations between participant constitutional genotype (buccal swab sample at enrollment), leukemia genotype (bone marrow aspirate at enrollment and upon relapse), and response to therapy.

Tumor RNA and participant RNA will be measured via RNA sequencing technique.

MTD is defined as the cohort of participants one cohort below the cohort that develop dose-limiting toxicity (DLT) in at least 2 participants.

Objective response, including complete remission (CR) plus complete remission with incomplete hematologic recovery (CRi), after induction therapy will be measured using the International Working Group (IWG) Response Criteria in acute myeloid leukemia (AML).

The proportion of patients who receive an allogeneic HSCT following a CR/CRi response will be reported along with an exact 95% confidence interval.

Evaluated in participants that achieve CR/CRi, and defined as number of days that elapse from first day CR/CRi to the first day that bone marrow blasts \>= 5%. The median duration of remission will be reported in patients who achieved CR/CRi, along with the corresponding range.

Measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

The diagnosis of veno-occlusive disease is based on the Baltimore criteria: Bilirubin \> 2.0 mg/dL, plus, painful hepatomegaly, ascites, and weight gain \> 5% basal since initiating therapy with gemtuzumab ozogamicin (GO). The proportion of patients who develop VOD will be reported along with an exact 95% confidence interval.

Defined as the number of days from day 1 of induction to ANC (absolute neutrophil count) \>= 1000/uL (upper limit) and platelet count \>= 100,000/uL. Will be reported along with the corresponding range.

Mortality is defined as death having occurred in any participant that receives at least one dose of experimental therapy. Kaplan-Meier methods will estimate the overall survival at day 30 and day 60 following the start of induction. The survival estimate at these two time points will be reported along with a 95% confidence interval.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Haematopoietic Stem Cell Transplantation (HSCT) in Comparison to Conventional Consolidation Therapy for Patients With Acute Myeloid Leukemia (AML) (Intermediate Risk) </= 60y. After First CR	NCT01246752	Leukemia, Myelo...	Human Stem Cell... Consolidation c...	18 Years - 60 Years	University Hospital Carl Gustav Carus
CPX-351 and Gemtuzumab Ozogamicin in Treating Patients With Relapsed Acute Myeloid Leukemia	NCT03904251	Acute Myelogeno...	Gemtuzumab Ozog... Liposome-encaps...	18 Years -	Jonsson Comprehensive Cancer Center

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