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

Primary Purpose

Hematopoietic and Lymphoid Cell Neoplasm

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Allogeneic Bone Marrow Transplantation

Allogeneic Hematopoietic Stem Cell Transplantation

Anti-Thymocyte Globulin

Bendamustine Hydrochloride

Fludarabine Phosphate

Inotuzumab Ozogamicin

Methotrexate

Peripheral Blood Stem Cell Transplantation

Rituximab

Tacrolimus

About this trial

This is an interventional treatment trial for Hematopoietic and Lymphoid Cell Neoplasm

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (transplant)

Arm 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.

Outcomes

Primary Outcome Measures

Maximum-tolerated dose (MTD) of inotuzumab ozogamicin

Defined as the highest dose for which the probability of toxicity is closest to 30%.

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.

Secondary Outcome Measures

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.

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.

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.

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.

Full Information

NCT ID

NCT01664910

First Posted

August 10, 2012

Last Updated

July 20, 2023

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01664910

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

October 29, 2012 (Actual)

Primary Completion Date

June 28, 2023 (Actual)

Study Completion Date

June 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematopoietic and Lymphoid Cell Neoplasm

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (transplant)

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Allogeneic Bone Marrow Transplantation

Other Intervention Name(s)

Allo BMT, Allogeneic BMT

Intervention Description

Undergo allogeneic BM transplant

Intervention Type

Procedure

Intervention Name(s)

Allogeneic Hematopoietic Stem Cell Transplantation

Other Intervention Name(s)

Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

Intervention Description

Undergo allogeneic PBSC or BM transplant

Intervention Type

Biological

Intervention Name(s)

Anti-Thymocyte Globulin

Other Intervention Name(s)

Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Bendamustine Hydrochloride

Other Intervention Name(s)

Bendamustin Hydrochloride, Cytostasan Hydrochloride, Levact, Ribomustin, SyB L-0501, Treanda

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Fludarabine Phosphate

Other Intervention Name(s)

2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Intervention Description

Given IV

Intervention Type

Biological

Intervention Name(s)

Inotuzumab Ozogamicin

Other Intervention Name(s)

Besponsa, CMC-544, Way 207294, WAY-207294

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Procedure

Intervention Name(s)

Peripheral Blood Stem Cell Transplantation

Other Intervention Name(s)

PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Intervention Description

Undergo allogeneic PBSC transplant

Intervention Type

Biological

Intervention Name(s)

Rituximab

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Other Intervention Name(s)

FK 506, Fujimycin, Hecoria, Prograf, Protopic

Intervention Description

Given IV or PO

Primary Outcome Measure Information:

Title

Maximum-tolerated dose (MTD) of inotuzumab ozogamicin

Description

Defined as the highest dose for which the probability of toxicity is closest to 30%.

Time Frame

Up to 30 days

Title

Incidence of dose-limiting toxicity

Description

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.

Time Frame

Up to 30 days

Secondary Outcome Measure Information:

Title

Objective overall response (complete remission and partial remission)

Description

Time Frame

Up to 3 years

Title

Overall survival (OS)

Description

Time Frame

Up to 3 years

Title

Recurrence-free survival

Description

Time Frame

Up to 3 years

Title

Cumulative incidence of acute and chronic graft versus host disease (GVHD)

Description

The method of Gooley et al will be used to estimate the cumulative incidence of acute and chronic GVHD.

Time Frame

Up to 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Issa Khouri

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

University of Texas MD Anderson Cancer Center Website

Learn more about this trial

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

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