CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies

NCT ID: NCT01664910

Last Updated: 2024-07-23

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-29

Study Completion Date

2023-06-28

Brief Summary

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This phase I/II trial studies the side effects and the best dose of inotuzumab ozogamicin when given together with fludarabine phosphate, bendamustine hydrochloride, and rituximab before donor stem cell transplant in treating patients with lymphoid malignancies. Giving chemotherapy drugs, such as fludarabine phosphate and bendamustine hydrochloride, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells or abnormal cell and helps stop the patient's immune system from rejecting the donor's stem cells. Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin and rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cell from a donor can make an immune system response against the body's normal cells. Giving fludarabine phosphate and bendamustine hydrochloride before the transplant together with anti-thymocyte globulin and tacrolimus may stop this from happening.

Detailed Description

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PRIMARY OBJECTIVES:

I. To characterize the safety of anti-cluster of differentiation (CD) 22 immunoconjugate inotuzumab ozogamicin (CMC-544), when administered in conjunction with fludarabine (fludarabine phosphate), bendamustine (bendamustine hydrochloride), and rituximab as non-myeloablative preparative regimen for allogeneic stem cell transplantation for CD22-positive lymphoid malignancies.

SECONDARY OBJECTIVES:

I. To estimate tumor response. II. To determine overall and event-free survival rates by histology subtype.

OUTLINE: This is a dose-escalation study of inotuzumab ozogamicin.

Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day -13, and fludarabine phosphate IV over 1 hour and bendamustine hydrochloride IV over 30 minutes to 1 hour on days -5 to -3. Patients with CD20-positive disease also receive rituximab IV over 4-6 hours on days -6, 1, and 8 and patients with matched unrelated donors (MUD) receive anti-thymocyte globulin IV over 3-4 hours on days -2 to -1. All patients also receive tacrolimus IV over 24 hours continuously or orally (PO) daily beginning on days -2 to 180 followed by taper in the absence of graft-versus-host disease (GVHD) and methotrexate IV over 30 minutes on days 1, 3, and 6 (1, 3, 6, and 11 in patients with MUD). Patients undergo allogeneic bone marrow (BM) or peripheral blood stem cell (PBSC) transplant on day 0.

After completion of study treatment, patients are followed up periodically.

Conditions

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Hematopoietic and Lymphoid Cell Neoplasm

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (transplant)

Patients receive inotuzumab ozogamicin IV over 1 hour on day -13, and fludarabine phosphate IV over 1 hour and bendamustine hydrochloride IV over 30 minutes to 1 hour on days -5 to -3. Patients with CD20-positive disease also receive rituximab IV over 4-6 hours on days -6, 1, and 8 and patients with MUD receive anti-thymocyte globulin IV over 3-4 hours on days -2 to -1. All patients also receive tacrolimus IV over 24 hours continuously or PO daily beginning on days -2 to 180 followed by taper in the absence of GVHD and methotrexate IV over 30 minutes on days 1, 3, and 6 (1, 3, 6, and 11 in patients with MUD). Patients undergo allogeneic BM or PBSC transplant on day 0.

Group Type EXPERIMENTAL

Allogeneic Bone Marrow Transplantation

Intervention Type PROCEDURE

Undergo allogeneic BM transplant

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo allogeneic PBSC or BM transplant

Anti-Thymocyte Globulin

Intervention Type BIOLOGICAL

Given IV

Bendamustine Hydrochloride

Intervention Type DRUG

Given IV

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Inotuzumab Ozogamicin

Intervention Type BIOLOGICAL

Given IV

Methotrexate

Intervention Type DRUG

Given IV

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo allogeneic PBSC transplant

Rituximab

Intervention Type BIOLOGICAL

Given IV

Tacrolimus

Intervention Type DRUG

Given IV or PO

Interventions

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Allogeneic Bone Marrow Transplantation

Undergo allogeneic BM transplant

Intervention Type PROCEDURE

Allogeneic Hematopoietic Stem Cell Transplantation

Undergo allogeneic PBSC or BM transplant

Intervention Type PROCEDURE

Anti-Thymocyte Globulin

Given IV

Intervention Type BIOLOGICAL

Bendamustine Hydrochloride

Given IV

Intervention Type DRUG

Fludarabine Phosphate

Given IV

Intervention Type DRUG

Inotuzumab Ozogamicin

Given IV

Intervention Type BIOLOGICAL

Methotrexate

Given IV

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Undergo allogeneic PBSC transplant

Intervention Type PROCEDURE

Rituximab

Given IV

Intervention Type BIOLOGICAL

Tacrolimus

Given IV or PO

Intervention Type DRUG

Other Intervention Names

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Allo BMT Allogeneic BMT Allogeneic Hematopoietic Cell Transplantation Allogeneic Stem Cell Transplantation HSC HSCT Antithymocyte Globulin Antithymocyte Serum ATG ATGAM ATS Thymoglobulin Bendamustin Hydrochloride Cytostasan Hydrochloride Levact Ribomustin SyB L-0501 Treanda 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara SH T 586 Besponsa CMC-544 Way 207294 WAY-207294 Abitrexate Alpha-Methopterin Amethopterin Brimexate CL 14377 CL-14377 Emtexate Emthexat Emthexate Farmitrexat Fauldexato Folex Folex PFS Lantarel Ledertrexate Lumexon Maxtrex Medsatrexate Metex Methoblastin Methotrexate LPF Methotrexate Methylaminopterin Methotrexatum Metotrexato Metrotex Mexate Mexate-AQ MTX Novatrex Rheumatrex Texate Tremetex Trexeron Trixilem WR-19039 PBPC transplantation PBSCT Peripheral Blood Progenitor Cell Transplantation Peripheral Stem Cell Support Peripheral Stem Cell Transplant Peripheral Stem Cell Transplantation ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Rituxan Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 RTXM83 FK 506 Fujimycin Hecoria Prograf Protopic

Eligibility Criteria

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Inclusion Criteria

* Patients with B-cell hematological malignancies who are eligible for allogeneic transplantation
* Patients must have a fully-matched sibling donor or a matched unrelated donor identified
* Performance score of at least 80% by Karnofsky or 0 to 2 Eastern Cooperative Oncology Group (ECOG)
* Left ventricular ejection fraction (EF) \>= 45% with no uncontrolled arrhythmias or symptomatic heart disease
* Forced expiratory volume in one second (FEV1) \>= 50%
* Forced vital capacity (FVC) \>= 50%
* Corrected diffusion capacity of the lung for carbon monoxide (DLCO) \>= 50%
* Serum creatinine \< 1.6 mg/dL
* Serum bilirubin \< 2 mg/dL upper limit of normal (unless due to Gilbert's disease; patient with this disease should have a right upper quadrant ultrasound evaluation before treatment)
* Serum glutamate pyruvate transaminase (SGPT) \< 2 x upper limit of normal
* Men and women of reproductive potential must agree to follow accepted birth control methods (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
* Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential (defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding; pregnancy testing is not required for post-menopausal or surgically sterilized women

Exclusion Criteria

* Patient with active central nervous system (CNS) involvement
* Known infection with human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV)-I, hepatitis B, or hepatitis C
* Patients with other malignancies diagnosed within 2 years prior to study registration; skin squamous or basal cell carcinoma are exceptions
* Active bacterial, viral or fungal infections
* History of stroke within 6 months
* History of biliary colic attack
* A prior autologous transplant within 3 months of study entry or allogeneic stem cell transplant
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study
* Patient has received other investigational drugs within 3 weeks before study registration
* Serious nonmalignant disease which, in the opinion of the investigator would compromise protocol objectives
* Prior exposure to CMC-544 within past 6 months
* Established refractoriness to CMC-544
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Issa Khouri

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

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NCI-2012-02072

Identifier Type: REGISTRY

Identifier Source: secondary_id

2012-0265

Identifier Type: OTHER

Identifier Source: secondary_id

2012-0265

Identifier Type: -

Identifier Source: org_study_id

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