Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Breast Neoplasms

Breast Neoplasms, Male

Breast Diseases

Skin Diseases

Breast Cancer, Male

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Annamycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

liposomal annamycin

Matthew D. Volm, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I/II trial to study the effectiveness of annamycin liposomal in treating patients who have locally advanced or metastatic breast cancer that has not responded to previous chemotherapy.

OBJECTIVES: I. Determine the observed anti-tumor activity of annamycin liposomal in patients with anthracycline-resistant locally advanced or metastatic breast cancer. II. Determine the qualitative and quantitative toxicity and reversibility of toxicity of this regimen in these patients. III. Determine the clinical pharmacology of this regimen in these patients. IV. Determine the rationale for the dose and chosen schedule of this regimen in these patients.

OUTLINE: Patients receive annamycin liposomal IV over 60 minutes on day 1. Treatment continues every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 14-30 patients will be accrued for this study within 7-30 months.

Chemotherapy in Treating Patients With Breast Cancer

Phase I/II Clinical and Pharmacological Study of Liposomal Annamycin in Anthracycline-Resistant Breast Cancer

National Cancer Institute (NCI)

NYU Langone Health

Blood and Lymph Conditions

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

2-hour intravenous infusion liposomal annamycin daily for 3 consecutive days followed by 18 days off study drug (i.e., one treatment cycle = 21 days).

Liposomal Annamycin

Robert Shepard, MD

This is a multi-center, open-label, dose escalation study that will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of liposomal annamycin as a single agent for the treatment of subjects with AML that is refractory to or relapsed after induction therapy

Enrollment will occur in cohorts of 3 subjects in a conventional 3+3 escalating dose design, starting at a dose level of 120 mg/m2/day administered for 3 days. Dose escalation will take place on the basis of safety assessments in sequential cohorts of 3 subjects each. The initial cohort will receive 120 mg/m2/day for 3 days. For Cohorts 1, 2, 3, 4, and 5, dose escalation will occur in 30-mg/m2/day increments until subjects are enrolled at a 240-mg/m2/day dose. For Cohorts 6, 7, and 8, dose escalation will occur in 60-mg/m2/day increments until subjects are enrolled at a maximum dose of 420 mg/m2/day. Thus subsequent cohorts will receive 150, 180, 210, 240, 300, 360, and up to a maximum of 420 mg/m2/day for 3 days in the absence of safety concerns.

In each cohort during the dose escalation phase, if 1 of the 3 subjects experiences a DLT, the cohort of subjects at that dose level will be expanded to 6 subjects. If at least 2 of the 6 subjects experience a DLT, this will be considered a toxic dose and the next 3 subjects will be treated at a lower dose. The dose will be de-escalated in 30-mg/m2/day increments. As such, if at least 2 out of 6 subjects receiving 300, 360, or 420 mg/m2/day experience a DLT, the next 3 subjects will receive 270, 330, or 390 mg/m2/day, respectively. The MTD is defined as the highest dose of L-Annamycin at which fewer than 2 (of a cohort of up to 6) subjects experience a DLT.

Once the MTD/RP2D is identified, up to 21 additional subjects will be enrolled at the MTD/RP2D to better define toxicity and evaluate efficacy at this dose.

Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML)

Phase 1/2 Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML) That is Refractory to or Relapsed After Induction Therapy

The number of patients who experience dose-limiting toxicities (DLT) will be captured at each dose level of L-Annamycin in order to determine the MTD/RP2D

Area under the plasma concentration - time curve (AUC) of annamycin and its metabolite, annamycinol

Determined by acute myeloid leukemia (AML) response rate based on the International Working Group (IWG) Response Criteria in AML (Cheson, 2003). Leukemia response rate will be evaluated by the investigator at the end of each L-Annamycin cycle based on bone marrow aspirate and peripheral blood evaluations.

Moleculin Biotech, Inc.

Immune System Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Gary Jacob, Ph.D.

This is a Phase I, multi-center, open-label, dose escalation, MTD study of liposomal annamycin in children and young adults with refractory or relapsed ALL or AML. Enrollment will occur in cohorts of approximately 3 subjects with 10 additional subjects enrolled at the MTD. The liposomal annamycin doses will be escalated in sequential cohorts. Six dose levels of liposomal annamycin are planned: 130, 160, 190, 230, 280, and 310 mg/m2/day.The primary objectives of this study are 1) to evaluate the safety and identify the maximum tolerated dose (MTD) of liposomal annamycin when given in 3 consecutive daily doses, starting at 130 mg/m2/day and ranging to as high as 310 mg/m2/day, or the MTD, whichever is lower, in children and young adults with refractory or relapsed acute lymphocytic leukemia (ALL) or acute myelogenous leukemia (AML), and 2) to evaluate the antileukemic activity of liposomal annamycin in children and young adults with refractory or relapsed ALL or AML. The secondary objective is to measure the pharmacokinetics of annamycin and its metabolite, annamycinol.

This is a Phase I, multi-center, open-label, dose escalation, MTD study of liposomal annamycin in children and young adults with refractory or relapsed ALL or AML. Enrollment will occur in cohorts of approximately 3 subjects with 10 additional subjects enrolled at the MTD. The liposomal annamycin doses will be escalated in sequential cohorts. Six dose levels of liposomal annamycin are planned: 130, 160, 190, 230, 280, and 310 mg/m2/day.

The initial group of 3 subjects will receive a treatment cycle of 130 mg/m2/day liposomal annamycin daily for 3 consecutive days followed by 18 days off liposomal annamycin (i.e., 1 treatment cycle = 21 days). A prophylactic mouthwash for use with anthracyline-based chemotherapies (composition described below under Test Product, Dose, and Mode of Administration) will be used 4 times a day on Days 1-4, with one of the 4 times being immediately 1 hour prior to liposomal annamycin treatment on Days 1 3, to prevent oral mucositis. Anti-allergic pre-medication with diphenydramine will be administered before each dose of liposomal annamycin.

Provided that no subject experiences dose limiting toxicity (DLT) \[defined as a study drug related Grade 3 or higher non-hematologic toxicity using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0\] during the first 21 days (i.e., during the first treatment cycle), the subsequent group of 3 subjects will receive the next higher liposomal annamycin dose. However, if 1 of the 3 initial subjects experiences DLT, the cohort of subjects at the initial dose level will be expanded to 6 subjects. If at least 2 of the 6 subjects experience DLT, then 3 subjects will be treated at the next lower dose. The MTD is defined as the highest dose of liposomal annamycin at which fewer than 2 (of a cohort of up to 6) subjects experience a DLT.

Subsequent dose escalation will occur in a similar fashion. If a subject discontinues treatment for reasons other than study drug related adverse events such that safety cannot be fully evaluated, an additional subject may be enrolled; these will be reviewed on a case-by-case basis in conjunction with the Sponsor. The dose will be escalated until either a MTD is identified or the maximum dose, 310 mg/m2/day, is achieved. Ten additional subjects will be enrolled at the MTD to better define toxicity and to better evaluate efficacy at the MTD.

Subjects will be evaluated before the start of liposomal annamycin treatment and during the first 3 days of liposomal annamycin treatment. Subjects will be evaluated weekly thereafter during the first cycle of treatment (1 cycle consists of 3 weeks, with 3 consecutive days of daily liposomal annamycin treatment followed by 18 days off of liposomal annamycin) and weekly during each subsequent cycle that they are eligible to receive further treatment. A follow-up visit will be conducted 1 to 2 weeks after the final treatment cycle or after the last study drug administration, if the treatment period was prematurely terminated.

Liposomal Annamycin in Children and Young Adults With Refractory or Relapsed ALL or AML

Phase I Study of Liposomal Annamycin in Children and Young Adults With Refractory or Relapsed Acute Lymphocytic Leukemia and Acute Myelogeneous Leukemia

Callisto Pharmaceuticals

Gary Jacob

This is a multi-center, open-label, dose escalation study that will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of liposomal annamycin as a single agent for the treatment of subjects with AML that is refractory to or relapsed after standard induction therapy

Phase 1/2 Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML) That is Refractory to or Relapsed After Standard Induction Therapy

Number of patients with a dose-limiting toxicity (DLT) at each dose evaluated

Determined by acute myeloid leukemia (AML) response rate based on the International Working Group (IWG) Response Criteria in AML (Cheson, 2003). Anti-leukemic Activity measured by bone marrow biopsy/aspirate pre and post treatment.

AEs were collected from safety population from the time of study treatment initiation until 39 days after the last dose of study treatment.

Safety population = all participants who received any amount of liposomal annamycin.

Liposomal Annamycin: 2-hour intravenous infusion liposomal annamycin daily for 3 consecutive days followed by 18 days off study drug (i.e., one treatment cycle = 21 days).

100 mg/m2 Dose Level

120 mg/m2 Dose Level

Dose Level 1: 100 mg/m2/Day Liposomal Annamycin

Dose Level 2: 120 mg/m2/Day Liposomal Annamycin

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

ECOG grading scale- 0 - Fully active, able to carry on all pre-disease performance without restriction

1- Restricted in physically strenuous activity but ambulatory and able to carry out work of a light of sedentary nature, e.g., light house work, office work 2 - Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours 3 - Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 4 - Completely disabled. Cannot carry on any self care. Totally confined to bed or chair.

5 - Dead

ECOG Performance Status

Chief Scientific Officer

Dose Level 2 : 120 mg/m2/Day Liposomal Annamycin

Dose-limiting Toxicity

Annamycin 100 mg/m2 - Day 1

Annamycin 100 mg/m2 - Day 3

Annamycin 120 mg/m2 - Day 1

Annamycin 120 mg/m2 - Day 3

Annamycinol 100 mg/m2 - Day 1

Annamycinol 100 mg/m2 - Day 3

Annamycinol 120 mg/m2 - Day 1

Annamycinol 120 mg/m2 - Day 3

One participant excluded from summary statistics due to high Annamycin concentrations

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chemotherapy in Treating Patients With Breast Cancer	NCT00012129	Breast Cancer	liposomal annam...	18 Years - 120 Years	NYU Langone Health
Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML)	NCT03388749	Leukemia, Myelo...	Liposomal Annam...	18 Years -	Moleculin Biotech, Inc.
Liposomal Annamycin in Children and Young Adults With Refractory or Relapsed ALL or AML	NCT00430443	Acute Lymphocyt... Acute Myelogeno...	Liposomal Annam...	12 Months - 21 Years	Callisto Pharmaceuticals
Chemotherapy in Treating Patients With Breast Cancer	NCT00012129	Breast Cancer	liposomal annam...	18 Years - 120 Years	NYU Langone Health
Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML)	NCT03315039	Leukemia, Myelo...	Liposomal Annam...	18 Years -	Moleculin Biotech, Inc.
Liposomal Annamycin in Children and Young Adults With Refractory or Relapsed ALL or AML	NCT00430443	Acute Lymphocyt... Acute Myelogeno...	Liposomal Annam...	12 Months - 21 Years	Callisto Pharmaceuticals
Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML)	NCT03315039	Leukemia, Myelo...	Liposomal Annam...	18 Years -	Moleculin Biotech, Inc.
Chemotherapy in Treating Patients With Breast Cancer	NCT00012129	Breast Cancer	liposomal annam...	18 Years - 120 Years	NYU Langone Health
Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML)	NCT03388749	Leukemia, Myelo...	Liposomal Annam...	18 Years -	Moleculin Biotech, Inc.

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