Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Primary Myelofibrosis

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Dendritic Cell Tumor

Blastic Plasmacytoid Dendritic Cell

Antineoplastic Agents

All Drugs and Chemicals

Lorvotuzumab mertansine

Maytansine

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

Lorvotuzumab mertansine (IMGN901) administered intravenously at a dose of 100 mg/m2 on Day 1 and 8 of a 21-day cycle.

100 mg/m2 by vein on Day 1 and 8 of a 21-day cycle.

Lorvotuzumab Mertansine (IMGN901)

Naval Daver, MD

The goal of this clinical research study is to learn if lorvotuzumab mertansine can help to control blood cancers that have the CD56 tumor marker. The safety of this drug will also be studied.

Study Treatment:

If you are found to be eligible to take part in this study, you will receive lorvotuzumab by vein on Days 1 and 8 (+/- 2 days) of each cycle. It may take a few minutes or several hours to receive the study drug. Your doctor will discuss this with you.

All treatments with IMGN901 must be administered at MD Anderson.

Each cycle is 21 days (+/-6 days). However, they may be longer or shorter depending on if/how the disease responds to the treatment, how your bone marrow reacts to treatment, and what the doctor thinks is in your best interest.

Your dose of lorvotuzumab may be raised, lowered, and/or delayed if the doctor thinks it is in your best interest.

Study Visits:

On Day 1 of each cycle, you will have a physical exam.

One (1) time each week during the first 4 cycles, blood (about 1 tablespoon) will be drawn for routine tests. After Cycle 4, you will have these blood draws 1 time every 2-4 weeks. If your doctor thinks it is needed, more blood may need to be drawn. The study doctor or study staff will discuss this with you if more blood is needed.

During the first cycle, all the laboratory evaluations will be done at MD Anderson. After Cycle 1, you may be able to have these blood draws performed at a local lab or clinic that is closer to your home, and the results reported to the research nurse of the study at MD Anderson. The study doctor or study staff will discuss this option with you. The results of these blood draws will be sent to the study doctor for review.

On Day 21 of Cycle 1 (+/- 7 days), then every 1-3 cycles after that, you will have a bone marrow aspiration/biopsy to check the status of the disease. If the doctor thinks it is needed, these may be done more or less often, depending on your response to the study drug.

You will have blood draws and/or bone marrow aspirations at any time that the doctor thinks it is needed while you are on study.

If you stay on study for more than 6 months and you are not having side effects, you may have some of the above tests more or less frequently. For example, you may only have a bone marrow aspiration 1 time every 6-12 months and blood draws 1 time each cycle. The study doctor will discuss this with you.

Length of Study:

You may take up to 12 cycles of lorvotuzumab. If the doctor thinks it is in your best interest, you may be able to continue receiving the study drug beyond Cycle 12. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after follow-up.

End-of-Study Visit:

If you leave the study before the end of Cycle 12, within 30 days (+/- 7 days) after the last dose of study drug:

* Blood (about 2-3 tablespoons) will be drawn for routine tests.
* If the doctor thinks it is needed, you will have a bone marrow aspirate/biopsy to check the status of the disease.

Long Term Follow-Up:

If the disease appears to get better and you are responding well to the study drug, you will return to MD Anderson every 3-6 months for up to 5 years after your last dose of study drug for the study staff to check how you are doing.

If you cannot return to MD Anderson for these visits, you may be called by a member of the study staff. The call should last about 10 minutes.

This is an investigational study. Lorvotuzumab is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the drug is designed to work.

Up to 60 participants will take part in this study. All will be enrolled at MD Anderson.

An Open-label Phase II Study of Lorvotuzumab Mertansine

An Open-label Phase II Study of Lorvotuzumab Mertansine (IMGN901) in CD56 Expressing Hematological Malignancies

ORR, defined as CR (complete remission) + CRp (complete remission with incomplete platelet recovery) + CRi (complete remission with incomplete count recovery) within 3 cycles of therapy with IMGN901.

ImmunoGen, Inc.

M.D. Anderson Cancer Center

Zero participants were registered on Cohort 2 (Myelofibrosis arm) or Cohort 3 (Blastic Plasmacytoid Dendritic Cell Neoplasm arm).

Lorvotuzumab mertansine (IMGN901) administered intravenously at a dose of 100 mg/m2 on Day 1 and 8 of a 21-day cycle.

Lorvotuzumab Mertansine (IMGN901): 100 mg/m2 by vein on Day 1 and 8 of a 21-day cycle.

Cohort 1: CD56 Expressing Hematological Malignancies

Cohort 2: Myelofibrosis

Cohort 3: Blastic Plasmacytoid Dendritic Cell Neoplasm

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Naval Daver, MD/ Associate Professor

Overall Response Rate (ORR) of IMGN901 in Participants CD56 Expressing Hematological Malignancies

Overall Study

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Recurrence

Neuroblastoma

Sarcoma

Wilms Tumor

Rhabdomyosarcoma

Sarcoma, Synovial

Nerve Sheath Neoplasms

Neurofibrosarcoma

Pulmonary Blastoma

Disease Attributes

Neoplasms, Connective and Soft Tissue

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Myosarcoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Neoplasms, Connective Tissue

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Fibrosarcoma

Neoplasms, Fibrous Tissue

Neurofibromatoses

Neurofibroma

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Soft Tissue Sarcoma

Wilms' Tumor

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

Pleuropulmonary Blastoma

Neuroepithelioma

Neurofibromatosis

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Ado-Trastuzumab Emtansine

Trastuzumab

Adenosine

Patients receive lorvotuzumab mertansine IV over 1-1.5 hours on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Lorvotuzumab Mertansine

Pharmacological Study

James I Geller

This phase II trial studies how well lorvotuzumab mertansine works in treating younger patients with Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, malignant peripheral nerve sheath tumor (MPNST), or synovial sarcoma that has returned or that does not respond to treatment. Antibody-drug conjugates, such as lorvotuzumab mertansine, are created by attaching an antibody (protein used by the body?s immune system to fight foreign or diseased cells) to an anti-cancer drug. The antibody is used to recognize tumor cells so the anti-cancer drug can kill them.

PRIMARY OBJECTIVES:

I. To assess the efficacy of IMGN901 (lorvotuzumab mertansine) in Wilms tumor, rhabdomyosarcoma, neuroblastoma and other cluster of differentiation (CD)56-expressing tumors such as pleuropulmonary blastoma, malignant peripheral nerve sheath tumor (MPNST) and synovial sarcoma.

II. To determine the tolerability of the adult recommended phase 2 dose (RP2D) of IMGN901 administered as an intravenous infusion, administered on days 1 and 8 of a 21-day cycle, to children with refractory Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, MPNST, or synovial sarcoma.

III. To define and describe the toxicities of IMGN901 administered on this schedule.

EXPLORATORY OBJECTIVES:

I. To correlate tumor response with tumor CD56+ expression. II. To characterize the pharmacokinetics of IMGN901 in children with refractory cancer, including an assessment of impact on circulating CD56+ peripheral blood cells.

OUTLINE:

Patients receive lorvotuzumab mertansine intravenously (IV) over 1-1.5 hours on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma

A Phase 2 Study of IMGN901 (Lorvotuzumab Mertansine; NSC#: 783609) in Children With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor (MPNST) and Synovial Sarcoma

A descriptive analysis of PK parameters of lorvotuzumab mertansine will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). Analyses will be descriptive and exploratory and hypotheses generating in nature.

The association between CD56+ expression and response will be evaluated using the exact conditional test of proportions (Fisher?s Exact test). Analyses will be descriptive and exploratory and hypotheses generating in nature.

The best response of disease will be examined separately in each stratum. A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and Clopper-Pearson confidence intervals will be constructed.

Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade for toxicities with Possible, Probable, or Definite attribution to the study drug. Tables will summarize incidence by cycle.

National Cancer Institute (NCI)

Children's Oncology Group

AE reporting is collected routinely using case report forms. The SAE table reflects NCI CTCAEs submitted by the institution, via expedited reporting (NCI AdEERs/CAeRs). The "AE Other" table reflects all CTCAEs collected; excludes those reported as SAEs. Patients who did not receive treatment before being take off study were not included in the AE tables; per protocol, AE data was not collected for those patients. Ineligible patients were excluded from both the AE and All-Cause Mortality tables.

ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles

Stratum 1: Wims Tumor

Stratum 2: Rhabdomyosarcoma

Stratum 3: Neuroblastoma

Stratum 4: Pleuropulmonary Blastoma

Stratum 5: Malignant Peripheral Nerve Sheath Tumor

Stratum 6: Synovial Sarcoma

Ethnicity (NIH/OMB)

Results Reporting Coordinator

2 participants were excluded from analysis; 1 participant never received treatment and 1 participant was ineligible, also never receiving treatment.

Objective Response by Response Evaluation Criteria in Solid Tumors Version 1.1

Anemia: Grade 2

Anemia: Grade 3

Anemia: Grade 4

Anemia: Grade 5

Colonic fistula: Grade 2

Colonic fistula: Grade 3

Colonic fistula: Grade 4

Colonic fistula: Grade 5

Colonic perforation: Grade 2

Colonic perforation: Grade 3

Colonic perforation: Grade 4

Colonic perforation: Grade 5

Dental caries: Grade 2

Dental caries: Grade 3

Dental caries: Grade 4

Dental caries: Grade 5

Nausea: Grade 2

Nausea: Grade 3

Nausea: Grade 4

Nausea: Grade 5

Vomiting: Grade 2

Vomiting: Grade 3

Vomiting: Grade 4

Vomiting: Grade 5

Tooth infection: Grade 2

Tooth infection: Grade 3

Tooth infection: Grade 4

Tooth infection: Grade 5

Alanine aminotransferase increased: Grade 2

Alanine aminotransferase increased: Grade 3

Alanine aminotransferase increased: Grade 4

Alanine aminotransferase increased: Grade 5

Aspartate aminotransferase increased: Grade 2

Aspartate aminotransferase increased: Grade 3

Aspartate aminotransferase increased: Grade 4

Aspartate aminotransferase increased: Grade 5

Lymphocyte count decreased: Grade 2

Lymphocyte count decreased: Grade 3

Lymphocyte count decreased: Grade 4

Lymphocyte count decreased: Grade 5

Hyperglycemia: Grade 2

Hyperglycemia: Grade 3

Hyperglycemia: Grade 4

Hyperglycemia: Grade 5

Hyperuricemia: Grade 2

Hyperuricemia: Grade 3

Hyperuricemia: Grade 4

Hyperuricemia: Grade 5

Hypokalemia: Grade 2

Hypokalemia: Grade 3

203 treatment-cycles were reported for the analysis. 2 participants were excluded from analysis;1 participant never received treatment and 1 participant was ineligible, also never receiving treatment.

Incidence of Toxicities of Lorvotuzumab Mertansine, Using the NCI Common Terminology Criteria for Adverse Events Version 4.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
An Open-label Phase II Study of Lorvotuzumab Mertansine	NCT02420873	Leukemia	Lorvotuzumab Me...	18 Years -	M.D. Anderson Cancer Center
Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma	NCT02452554	Pleuropulmonary... Recurrent Malig... Recurrent Neuro... Recurrent Rhabd... Recurrent Synov... Wilms Tumor	Laboratory Biom... Lorvotuzumab Me... Pharmacological...	12 Months - 30 Years	Children's Oncology Group

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