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

M.D. Anderson Cancer Center

Status and phase

Completed

Phase 2

Phase 1

Conditions

Hematopoietic and Lymphoid Cell Neoplasm

Treatments

Drug: Fludarabine Phosphate

Drug: Methotrexate

Procedure: Allogeneic Bone Marrow Transplantation

Biological: Inotuzumab Ozogamicin

Drug: Tacrolimus

Drug: Bendamustine Hydrochloride

Biological: Rituximab

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Procedure: Peripheral Blood Stem Cell Transplantation

Biological: Anti-Thymocyte Globulin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01664910

NCI-2012-02072 (Registry Identifier)

2012-0265 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

27 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

27 participants in 1 patient group

Treatment (transplant)

Experimental group

Description:

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.

Treatment: