CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies
The goal of this clinical research study is to learn which dose level of inotuzumab ozogamicin (CMC-544) work best when given with fludarabine and bendamustine, with or without rituximab, before a stem cell transplant.The safety of this treatment will also be studied.
Fludarabine, bendamustine, and rituximab are commonly given before stem cell transplants. These drugs are designed to kill cancerous cells and suppress your immune system in order to lower the risk of stem cell transplant rejection.
Inotuzumab ozogamicin is designed to kill cancerous cells and reduce the risk of the cancer coming back.
|Lymphoma Leukemia||Drug: CMC-544 Drug: Fludarabine Drug: Bendamustine Drug: Rituximab Procedure: Allogeneic Stem Cell Transplantation Drug: Thymoglobulin Drug: Tacrolimus Drug: Methotrexate Drug: G-CSF||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) Added to Fludarabine, Bendamustine and Rituximab and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies|
- Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin (CMC-544) [ Time Frame: 1 month ]The MTD is defined as the highest dose for which the probability of toxicity is closest to 30%. The dose-limiting toxicity (DLT) is defined as grade III or IV renal, hepatic, intestinal, neurologic, pulmonary or cardiac adverse events, as well as any graft failure or treatment-related death at any time from first CMC-544 administration (D-13) through 30 days post transplant (D30).
- Overall Survival [ Time Frame: 3 months ]Objective overall response estimated (complete response and partial response) with a 95% confidence interval in dose that is declared MTD. Logistic regression used to assess association between response and disease and clinical characteristics of interest. Kaplan-Meier survival curves used to estimate overall survival and recurrence-free survival. Cox proportional hazards regression methodology used to assess association between disease and clinical characteristics and survival outcomes.
|Actual Study Start Date:||October 2012|
|Estimated Study Completion Date:||October 2018|
|Estimated Primary Completion Date:||October 2018 (Final data collection date for primary outcome measure)|
Experimental: Inotuzumab Ozogamicin (CMC-544) + Chemotherapy
D-13, CMC-544 infused intravenously (IV) on Day -13. Starting dose per cohort: 0.6,1.2 or 1.8 mg/m2. Dose based on actual body weight. Fludarabine 30 mg/m2 IV followed by Bendamustine 130 mg/m2 IV on Days -5 to -3. Patients with CD20+ disease also receive Rituximab IV at 375 mg/m2 on Days -6, +1 and +8. Allogeneic stem cell transplantation on Day 0. Thymoglobulin 1 mg/kg administrated IV on Days -2 and -1 to patients receiving a matched unrelated donor (MUD). Tacrolimus on Day -2 administered at starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after day +90 if no GVHD is present.
0.6, 1.2 or 1.8 mg/m2 (dose is based on actual body weight) by vein on Day -13.
Other Name: Inotuzumab OzogamicinDrug: Fludarabine
30 mg/m2 by vein on Days -5, -4 and -3.
Other Names:Drug: Bendamustine
130 mg/m2 by vein on Days -5, -4 and -3.
Other Names:Drug: Rituximab
375 mg/m2 by vein (based on actual body weight) on Day -6, Day +1 and +8 for patients with CD20+ disease.
Other Name: RituxanProcedure: Allogeneic Stem Cell Transplantation
Allogeneic stem cell transplantation on Day 0.Drug: Thymoglobulin
1 mg/kg (based on actual body weight) by vein patients receiving a matched unrelated donor (MUD) on Days -2 and -1.
Other Names:Drug: Tacrolimus
0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion on Day -2, daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after Day +90 if no graft versus host disease (GVHD) is present.
Other Name: PrografDrug: Methotrexate
5 mg/m2 by vein on Days +1, +3, and +6 for all patients. Patients receiving an unrelated graft will also be given Methotrexate on Day +11 after the transplant.Drug: G-CSF
5 mcg/kg/day subcutaneously beginning on Day +7 for patients receiving related and MUD. G-CSF will continue until the absolute neutrophil count (ANC) is > 500 x 10/L for 3 consecutive days.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01664910
|Contact: Issa F. Khouri, MD, BS||713-792-8750|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Issa F. Khouri, MD, BS||M.D. Anderson Cancer Center|