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Pharmacologic Pretransplant Immunosuppression (PTIS) + Reduced Toxicity Conditioning (RTC) Allogeneic Stem Cell Transplantation in Inherited Hematologic Disorders

Primary Purpose

Stem Cell Transplantation

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Fludarabine

Dexamethasone

Cyclophosphamide

Bortezomib

Rituximab

Busulfan

Cyclophosphamide (Cy)

Tacrolimus (or cyclosporine)

Mycophenolate mofetil (MMF)

Rabbit ATG

About this trial

This is an interventional treatment trial for Stem Cell Transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

The first six patients will be ages >12 years old and <35 years old. Thereafter in a second stage, patients ages 2 to 50 years old will be included.
Patient with a matched related donor or who has a related haploidentical donor identified.
Performance score of at least 70 by Karnofsky or 0 to 1 by ECOG (age > 12 years), or Zubrod or Lansky Play Performance Scale of at least 70 (age <12 years).
Adequate major organ system function as demonstrated by:
1. Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockroft-Gault formula).
2. Bilirubin equal or less than 1.5 mg/dl except for Gilbert's disease. ALT and/or AST equal or less than 3x institutional ULN. Conjugated (direct) bilirubin less than 2x upper limit of normal.
3. Left ventricular ejection fraction equal or greater than 50%.
4. Diffusing capacity for carbon monoxide (DLCO) equal or greater than 50%
5. Predicted, corrected for hemoglobin. For children < 7 years of age who are unable to perform PFT, oxygen saturation > 92% on room air by pulse oximetry.
Patient or the patient's legal representative, parent(s) or guardian should be able to provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years.
Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator.

Exclusion Criteria:

HIV positive; active hepatitis B or C.
Uncontrolled infections.
Liver cirrhosis. However mild fibrosis will be allowed i.e. fine reticulin or Grade 1, with bridging fibrosis.
CNS involvement within 3 months.
Positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
Inability to comply with medical therapy or follow-up.
Will restrict eligibility to a maximum BMI of ≤40
Patient with a known history of allergic reactions to any constituents of the cell product, including a known history of allergic reactions to DMSO.
Prior allo-SCT
Other active malignancy/cancer diagnosis in remission for at least 2yrs. Malignancies not being excluded are as follows: Ductal carcinoma in situ (DCIS), Basal cell carcinoma (BCC), Cervical intraepithelial neoplasia (CIN)

Sites / Locations

M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Phase I: Sequential Pharmacological PTIS

Phase II: RTC Regimen and GVHD Prophylaxis Based on Post-Cy

Arm Description

Outcomes

Primary Outcome Measures

To determine the 100-day non-relapse mortality (NRM) rate when administering pharmacologic pretransplant immunosuppression (PTIS) followed by pretransplant reduced toxicity conditioning (RTC

Secondary Outcome Measures

Full Information

NCT ID

NCT05293509

First Posted

March 4, 2022

Last Updated

September 18, 2023

Sponsor

M.D. Anderson Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT05293509

Brief Title

Pharmacologic Pretransplant Immunosuppression (PTIS) + Reduced Toxicity Conditioning (RTC) Allogeneic Stem Cell Transplantation in Inherited Hematologic Disorders

Official Title

Pharmacologic Pretransplant Immunosuppression (PTIS) + Reduced Toxicity Conditioning (RTC) Allogeneic Stem Cell Transplantation in Inherited Hematologic Disorders

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Withdrawn

Why Stopped

0 accrual

Study Start Date

March 2, 2022 (Actual)

Primary Completion Date

September 18, 2023 (Actual)

Study Completion Date

September 18, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

To assess the outcomes of NRM when administering pharmacologic pretransplant immunosuppression (PTIS) followed by pretransplant reduced toxicity conditioning (RTC) and an allogeneic stem cell transplant (allo-SCT) and post-transplant graft-versus-host disease prophylaxis based on post-transplant cyclophosphamide (PT-Cy) in patients with inherited blood disorders.

Detailed Description

Objectives Primary: To estimate the 100-day non-relapse mortality (NRM) rate when administering pharmacologic pretransplant immunosuppression (PTIS) followed by pretransplant reduced toxicity conditioning (RTC) and an allogeneic stem cell transplant (allo-SCT) and post-transplant graft-versus-host disease prophylaxis based on post-transplant cyclophosphamide (PT-Cy) in patients with inherited blood disorders. Secondary outcomes include the following: i. Immune reconstitution ii. Infectious complications iii. Quality of life (QOL) at 3 months,100 days, and 1 year post-transplant iv. OS, EFS, and GRFS v. Incidence of aGVHD at day 100. vi. Rate of chronic GVHD within the first-year post transplantation. vii. Rate of Graft failure

6. Conditions and Keywords

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

Stem Cell Transplantation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase I: Sequential Pharmacological PTIS

Arm Type

Experimental

Arm Title

Phase II: RTC Regimen and GVHD Prophylaxis Based on Post-Cy

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Other Intervention Name(s)

Fludara™

Intervention Description

40 mg/m2/day i.v.- by vein

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

25 mg/m2/day i.v.-by vein

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan™

Intervention Description

100 mg/m2 IV-by vein

Intervention Type

Drug

Intervention Name(s)

Bortezomib

Other Intervention Name(s)

Velcade®

Intervention Description

Four doses of bortezomib at a dose of 1.3 mg/m2 -injection under the skin

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

Rituxan®

Intervention Description

Four doses of rituximab at a dose of 375 mg/m2- by vein

Intervention Type

Drug

Intervention Name(s)

Busulfan

Other Intervention Name(s)

Busulfex™

Intervention Description

110 mg/m2 i.v-by vein

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide (Cy)

Other Intervention Name(s)

Cytoxan™

Intervention Description

by vein

Intervention Type

Drug

Intervention Name(s)

Tacrolimus (or cyclosporine)

Intervention Description

by vein

Intervention Type

Drug

Intervention Name(s)

Mycophenolate mofetil (MMF)

Intervention Description

given by PO

Intervention Type

Drug

Intervention Name(s)

Rabbit ATG

Intervention Description

by vein

Primary Outcome Measure Information:

Title

To determine the 100-day non-relapse mortality (NRM) rate when administering pharmacologic pretransplant immunosuppression (PTIS) followed by pretransplant reduced toxicity conditioning (RTC

Time Frame

through study completion, an average of 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: The first six patients will be ages >12 years old and <35 years old. Thereafter in a second stage, patients ages 2 to 50 years old will be included. Patient with a matched related donor or who has a related haploidentical donor identified. Performance score of at least 70 by Karnofsky or 0 to 1 by ECOG (age > 12 years), or Zubrod or Lansky Play Performance Scale of at least 70 (age <12 years). Adequate major organ system function as demonstrated by: Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockroft-Gault formula). Bilirubin equal or less than 1.5 mg/dl except for Gilbert's disease. ALT and/or AST equal or less than 3x institutional ULN. Conjugated (direct) bilirubin less than 2x upper limit of normal. Left ventricular ejection fraction equal or greater than 50%. Diffusing capacity for carbon monoxide (DLCO) equal or greater than 50% Predicted, corrected for hemoglobin. For children < 7 years of age who are unable to perform PFT, oxygen saturation > 92% on room air by pulse oximetry. Patient or the patient's legal representative, parent(s) or guardian should be able to provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years. Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator. Exclusion Criteria: HIV positive; active hepatitis B or C. Uncontrolled infections. Liver cirrhosis. However mild fibrosis will be allowed i.e. fine reticulin or Grade 1, with bridging fibrosis. CNS involvement within 3 months. Positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization. Inability to comply with medical therapy or follow-up. Will restrict eligibility to a maximum BMI of ≤40 Patient with a known history of allergic reactions to any constituents of the cell product, including a known history of allergic reactions to DMSO. Prior allo-SCT Other active malignancy/cancer diagnosis in remission for at least 2yrs. Malignancies not being excluded are as follows: Ductal carcinoma in situ (DCIS), Basal cell carcinoma (BCC), Cervical intraepithelial neoplasia (CIN)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeremy Ramdial, Ramdial

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

M D Anderson Cancer Center

Learn more about this trial

Pharmacologic Pretransplant Immunosuppression (PTIS) + Reduced Toxicity Conditioning (RTC) Allogeneic Stem Cell Transplantation in Inherited Hematologic Disorders

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