Neoplasms

Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Rare Diseases

Neoplasm Metastasis

Leukemia

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasm, Residual

Hematologic Diseases

Neoplasms by Histologic Type

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Interleukin-2

Antineoplastic Agents, Alkylating

Cyclophosphamide + Fludarabine prior to CYNK-001 on Days 0, 7, and 14; CYNK-001 at 3 varying dose levels.

CYNK-001 is an allogeneic off the shelf cell therapy enriched for CD56+/CD3- NK cells expanded from human placental CD34+ cells.

CYNK-001

Cherie Daly, MD

Michael Maris, MD

Hongtao Liu, MD, PhD

James McCloskey, MD

Eunice Wang, MD

Joseph Jurcic, MD, PhD

Lauren Harrison, MSN

Mitchell Cairo, MD

Amir Steinberg, MD

William Donnellan, MD

Melissa Cabrera, BS

Naveen Pemmaraju, MD

Daniel Egan, MD

This study will find the maximum tolerated dose or the maximum planned dose of CYNK-001 which contains natural killer (NK) cells derived from human placental CD34+ cells and culture-expanded. CYNK-001 cells will be given after lymphodepleting chemotherapy. The safety of this treatment will be evaluated, and researchers want to learn if NK cells will help in treating acute myeloid leukemia.

Experimental: Minimal Residual Disease (MRD) positive AML patients; Cyclophosphamide + Fludarabine + CYNK-001. On Days 0, 7, and 14, (and 21 in certain arms) CYNK-001 at 3 varying dose levels.

Experimental: Relapsed/Refractory AML patients; Cyclophosphamide + Fludarabine + CYNK-001. On Days 0, 7, and 14, (and 21 at certain dose levels) CYNK-001 at 3 varying dose levels.

Natural Killer Cell (CYNK-001) Infusions in Adults With AML

A Phase I Multi-dose Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK-001) With or Without Recombinant Human Interleukin-2 (rhIL-2) in Adults With Primary or Secondary Acute Myeloid Leukemia (AML) in Morphologic Complete Remission With Minimal Residual Disease (MRD) or Relapsed/Refractory (R/R) AML

The number of participants who experience a DLT will be measured.

The maximum dose safely administered for the treatment of patients with AML.

Frequency and severity of Adverse Events will be evaluated.

The number of participants who convert from MRD positive to MRD negative in the MRD positive arm.

The time it takes to convert from MRD positive to MRD negative in the MRD positive arm.

The measure of how long participants remain MRD negative in the MRD positive arm.

Date of first CYNK-001 infusion to date of disease progression in the MRD positive arm.

Duration from first Morphologic CR observation to time of disease progression in the MRD positive arm.

Date of first CYNK-001 infusion to date of death.

Defined as achievement of Complete Remission (CR), Complete Remission with incomplete (CRi) hematologic recovery, or Morphologic leukemic-free state (MLFS) in the Relapsed/Refractory AML arm.

Duration of best response in the Relapsed/Refractory AML arm.

Celularity Incorporated

Heart and Blood Diseases

Immune System Diseases

Skin and Connective Tissue Diseases

Recurrence

Heart Failure

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Osteosarcoma

Lymphoma

Cardiomyopathies

Hodgkin Disease

Leukemia, Lymphoid

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Heart Diseases

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Hodgkin Lymphoma

Soft Tissue Sarcoma

Cardiotonic Agents

Dexrazoxane

Razoxane

Patients complete a diagnostic symptom checklist, undergo a physical exam, echocardiogram, collection of serum for biomarker testing, and a 6 minute walk test, and complete quality of life, family history, physical activity, and smoking questionnaires.

Assessment of Therapy Complications

Laboratory Biomarker Analysis

Quality-of-Life Assessment

Questionnaire Administration

Site Public Contact

Smita Bhatia

Alexandra M. Walsh

Holly E. Pariury

David L. Becton

Saro H. Armenian

Laura A. Campbell

Jay Michael S. Balagtas

William D. Roberts

Nina S. Kadan-Lottick

Emad K. Salman

Ramamoorthy Nagasubramanian

Dana A. Obzut

Narayana Gowda

Lillian R. Meacham

Wade T. Kyono

Jennifer L. Reichek

Rebecca E. McFall

Jaime M. Libes

Craig Lotterman

Eric C. Larsen

Jason M. Fixler

Kenneth J. Cohen

Lynda M. Vrooman

Adonis N. Lorenzana

Anderson (Andy) B. Collier

Robert J. Hayashi

Alan K. Ikeda

Michael B. Harris

John F. Kuttesch

Jonathan D. Fish

Angela R. Girvin

Laura E. Hogan

Philip M. Monteleone

Douglas J. Scothorn

Thomas B. Russell

Steven J. Kuerbitz

Rajaram Nagarajan

Rene Y. McNall-Knapp

Janice F. Olson

Susan J. Lindemulder

Gregory E. Halligan

Jennifer J. Greene Welch

Jacqueline M. Kraveka

Nichole L. Bryant

Daniel C. Bowers

Julienne Brackett

Anne-Marie R. Langevin

Jessica L. Heath

Madhu S. Gowda

Douglas S. Hawkins

Judy L. Felgenhauer

Richard L. Tower

Marianne B. Phillips

Douglas R. Strother

Sharon B. Abish

Yvan Samson

Bruno Michon

Luis A. Clavell

Eric J Chow

This clinical trial studies the effects of dexrazoxane hydrochloride on biomarkers associated with cardiomyopathy and heart failure after cancer treatment. Studying samples of blood in the laboratory from patients receiving dexrazoxane hydrochloride may help doctors learn more about the effects of dexrazoxane hydrochloride on cells. It may also help doctors understand how well patients respond to treatment.

PRIMARY OBJECTIVES:

I. To determine whether leukemia and lymphoma patients from P9404, P9425, P9426, and Dana Farber Cancer Institute (DFCI) 95-01 randomized to the experimental dexrazoxane hydrochloride (DRZ) arms have decreased markers of cardiomyopathy/heart failure (CHF) compared with patients on the standard arm.

II. To determine whether osteosarcoma patients from P9754 (all received DRZ) have decreased markers of cardiomyopathy/heart failure (CHF) compared with similarly treated osteosarcoma patients diagnosed during the same time period, but who did not receive DRZ.

III. To evaluate whether the cardioprotective effect of DRZ is modified by anthracycline (anthracycline analogue GPX-150) dose, chest radiation, and demographic factors (age at cancer diagnosis, current age, sex).

SECONDARY OBJECTIVES:

I. To determine whether leukemia and lymphoma patients from P9404, P9425, P9426, and DFCI 95-01 on the DRZ arms experienced differential rates of overall-survival and event-free survival compared with the standard therapy arms.

II. To determine whether projected quality-adjusted life years (QALY) differed by DRZ status, accounting for premature cardiac disease, primary disease relapse, and second cancers.

III. Determine the longitudinal trajectory of 2-dimensional echocardiographic parameters (focusing on left ventricular \[LV\] function and remodeling/geometric changes that can be reliably re-measured) among patients from time of cancer treatment through subsequent follow-up.

OUTLINE:

Patients complete a diagnostic symptom checklist, undergo a physical exam, echocardiogram, collection of serum for biomarker testing, and a 6 minute walk test, and complete quality of life, family history, physical activity, and smoking questionnaires.

Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment

Health Effects After Anthracycline and Radiation Therapy (HEART): Dexrazoxane and Prevention of Anthracycline-Related Cardiomyopathy

Univariate tests will be used as well as examination of the entire cohort via multivariable regression adjusting for all a priori covariates of interest.

An analytic Markov model will be created and used. Estimates and their 95% confidence will be included to explore the sensitivity of any quality-adjusted life years estimates.

An analytic Markov model will be created and used.

Will utilize generalized linear model-general estimation equation to model the trajectories of echocardiographic biomarker estimates (continuous outcomes) across time. Relevant model shapes will be evaluated, beginning with linear models, but also testing more flexible shapes (e.g., quadratic, cubic, or cubic spline functions with varying numbers of knots) to determine whether non-linear components are needed for fit. Will also examine interactions of dexrazoxane (DRZ) status with the selected functions of time to evaluate for differences in trajectories over time by DRZ status.

National Cancer Institute (NCI)

Children's Oncology Group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Natural Killer Cell (CYNK-001) Infusions in Adults With AML	NCT04310592	Leukemia Leukemia, Myelo... Leukemia, Myelo... Neoplasms by Hi... Neoplasms Immunosuppressi... Immunologic Fac... Physiological E... Alkylating Agen... Antimetabolites... Antiviral Agent... Analgesics, Non... Anti-infective ... Analgesics Peripheral Nerv... Hematologic Dis... Hematologic Neo... Leukemia in Rem... Relapsed Adult ... Refractory AML	CYNK-001	18 Years - 80 Years	Celularity Incorporated
Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment	NCT01790152	Hodgkin Lymphom... Leukemia in Rem... Lymphoblastic L... Osteosarcoma Recurrent Leuke... Recurrent Lymph... Recurrent Malig...	Assessment of T... Laboratory Biom... Quality-of-Life... Questionnaire A...	-	Children's Oncology Group
Natural Killer Cell (CYNK-001) Infusions in Adults With AML	NCT04310592	Leukemia Leukemia, Myelo... Leukemia, Myelo... Neoplasms by Hi... Neoplasms Immunosuppressi... Immunologic Fac... Physiological E... Alkylating Agen... Antimetabolites... Antiviral Agent... Analgesics, Non... Anti-infective ... Analgesics Peripheral Nerv... Hematologic Dis... Hematologic Neo... Leukemia in Rem... Relapsed Adult ... Refractory AML	CYNK-001	18 Years - 80 Years	Celularity Incorporated

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