Hematopoietic and Lymphoid Cell NeoplasmPhase 1/2NCT01664910
CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies
A Phase 1/2 study testing Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation and Anti-Thymocyte Globulin in people with Hematopoietic and Lymphoid Cell Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hematopoietic and Lymphoid Cell Neoplasm
- What is being tested?
- Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation and Anti-Thymocyte Globulin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Oct 2012to 28 Jun 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Show all 12Show fewer
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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
- Hematopoietic and Lymphoid Cell Neoplasm
- Being tested
- Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation, Anti-Thymocyte Globulin, Bendamustine Hydrochloride, Fludarabine Phosphate
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Bone Marrow TransplantationProcedure or surgery
Also called Allo BMT, Allogeneic BMT
Undergo allogeneic BM transplant
Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT
Undergo allogeneic PBSC or BM transplant
Anti-Thymocyte GlobulinBiological
Also called Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM
Given IV
Bendamustine HydrochlorideDrug
Also called Bendamustin Hydrochloride, Cytostasan Hydrochloride, Levact, Ribomustin
Given IV
Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara
Given IV
Inotuzumab OzogamicinBiological
Also called Besponsa, CMC-544, Way 207294, WAY-207294
Given IV
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IV
Peripheral Blood Stem Cell TransplantationProcedure or surgery
Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support
Undergo allogeneic PBSC transplant
RituximabBiological
Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody
Given IV
TacrolimusDrug
Also called FK 506, Fujimycin, Hecoria, Prograf
Given IV or PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (transplant) | Experimental | 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. Receives: Procedure: Allogeneic Bone Marrow Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: Anti-Thymocyte Globulin; Drug: Bendamustine Hydrochloride; Drug: Fludarabine Phosphate; Biological: Inotuzumab Ozogamicin; Drug: Methotrexate; Procedure: Peripheral Blood Stem Cell Transplantation; Biological: Rituximab; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum-tolerated Dose (MTD) of Inotuzumab Without DLT
Number of participants received inotuzumab in each cohort without DLT
Measured: Up to 30 days
Secondary outcomes (2)
Overall Response
Overall response (CR+PR) with estimated with a 95% confidence interval in the dose that is declared the MTD. Complete Response is no clinical or radiological evidence of disease. Partial remission is equal to or more than 50% reduction in lymphadenopathy, liver and or spleen if abnormal at pre-treatment.
Measured: Up to 3 years
Overall Survival (OS)
Participants are disease free and alive at 3 years post transplant.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2012 (estimated)
- Study start29 Oct 2012
- Primary completion28 Jun 2023
- Study completion28 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hematopoietic and Lymphoid Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Issa Khouri, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01664910
- Sponsor's protocol ID
- 2012-0265
- Other IDs
- NCI-2012-02072, 2012-0265
- Status last verified
- Jun 2024
- First submitted
- 10 Aug 2012
- Last updated
- 23 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) Added to Fludarabine, Bendamustine and Rituximab and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT01664910
- Acronym / sponsor ID
- 2012-0265
- Conditions
- Hematopoietic and Lymphoid Cell Neoplasm
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 29 Oct 2012 (actual)
- Primary completion
- 28 Jun 2023 (actual)
- Study completion
- 28 Jun 2023 (actual)
- First posted
- 14 Aug 2012 (estimated)
- Results
- Posted 23 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (transplant) | Experimental | Procedure: Allogeneic Bone Marrow Transplantation, Procedure: Allogeneic Hematopoietic Stem Cell Transplantation, Biological: Anti-Thymocyte Globulin, Drug: Bendamustine Hydrochloride, Drug: Fludarabine Phosphate, Biological: Inotuzumab Ozogamicin, Drug: Methotrexate, Procedure: Peripheral Blood Stem Cell Transplantation, Biological: Rituximab, Drug: TacrolimusPatients 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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%
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogeneic Bone Marrow TransplantationAlso: Allo BMT, Allogeneic BMTUndergo allogeneic BM transplant | Procedure or surgery | Treatment (transplant) |
| Allogeneic Hematopoietic Stem Cell TransplantationAlso: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCTUndergo allogeneic PBSC or BM transplant | Procedure or surgery | Treatment (transplant) |
| Anti-Thymocyte GlobulinAlso: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAMGiven IV | Biological | Treatment (transplant) |
| Bendamustine HydrochlorideAlso: Bendamustin Hydrochloride, Cytostasan Hydrochloride, Levact, RibomustinGiven IV | Drug | Treatment (transplant) |
| Fludarabine PhosphateAlso: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, FludaraGiven IV | Drug | Treatment (transplant) |
| Inotuzumab OzogamicinAlso: Besponsa, CMC-544, Way 207294, WAY-207294Given IV | Biological | Treatment (transplant) |
| MethotrexateAlso: Abitrexate, Alpha-Methopterin, Amethopterin, BrimexateGiven IV | Drug | Treatment (transplant) |
| Peripheral Blood Stem Cell TransplantationAlso: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell SupportUndergo allogeneic PBSC transplant | Procedure or surgery | Treatment (transplant) |
| RituximabAlso: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 AntibodyGiven IV | Biological | Treatment (transplant) |
| TacrolimusAlso: FK 506, Fujimycin, Hecoria, PrografGiven IV or PO | Drug | Treatment (transplant) |
Primary outcome
Maximum-tolerated Dose (MTD) of Inotuzumab Without DLT
Time frame: Up to 30 days
Number of participants received inotuzumab in each cohort without DLT
2 secondary outcomes
Overall Response
Time frame: Up to 3 years
Overall Survival (OS)
Time frame: Up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Issa Khouri principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation and Anti-Thymocyte Globulin in people with Hematopoietic and Lymphoid Cell Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum-tolerated Dose (MTD) of Inotuzumab Without DLT (time frame: Up to 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2024.