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

Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) Added to Fludarabine, Bendamustine and Rituximab and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies

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.

Study Overview

• Status: Completed
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm
• Intervention / Treatment: Drug: Methotrexate; Biological: Rituximab; Biological: Inotuzumab Ozogamicin; Procedure: Allogeneic Bone Marrow Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: Anti-Thymocyte Globulin; Drug: Bendamustine Hydrochloride; Drug: Fludarabine Phosphate; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Tacrolimus

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum-tolerated dose (MTD) of inotuzumab ozogamicin	Defined as the highest dose for which the probability of toxicity is closest to 30%.	Up to 30 days
Incidence of dose-limiting toxicity	Defined as grade III or IV renal, hepatic, intestinal, neurologic, pulmonary or cardiac adverse events, as well as graft failure or death at any time.	Up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective overall response (complete remission and partial remission)	Estimated with a 95% confidence interval in the dose that is declared the MTD. Logistic regression will be used to assess the association between response and disease and clinical characteristics of interest.	Up to 3 years
Overall survival (OS)	Kaplan-Meier survival curves will be used to estimate OS. Cox proportional hazards regression methodology will be used to assess the association between disease and clinical characteristics and the survival outcomes.	Up to 3 years
Recurrence-free survival	Kaplan-Meier survival curves will be used to estimate recurrence-free survival. Cox proportional hazards regression methodology will be used to assess the association between disease and clinical characteristics and the survival outcomes.	Up to 3 years
Cumulative incidence of acute and chronic graft versus host disease (GVHD)	The method of Gooley et al will be used to estimate the cumulative incidence of acute and chronic GVHD.	Up to 3 years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Issa Khouri, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2012
• Primary Completion (Actual): June 28, 2023
• Study Completion (Actual): June 28, 2023

Study Registration Dates

• First Submitted: August 10, 2012
• First Submitted That Met QC Criteria: August 10, 2012
• First Posted (Estimated): August 14, 2012

Study Record Updates

• Last Update Posted (Actual): July 21, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Dermatologic Agents; Antibiotics, Antineoplastic; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Calcineurin Inhibitors; Immunoconjugates; Immunotoxins; Antibodies; Immunoglobulins; Bendamustine Hydrochloride; Rituximab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Fludarabine; Fludarabine phosphate; Methotrexate; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Inotuzumab Ozogamicin
• Other Study ID Numbers: 2012-0265 (Other Identifier: M D Anderson Cancer Center); NCI-2012-02072 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No