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

NCT05293509 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-0477NCI-2022-02150
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

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

  through study completion, an average of 1 year

Study Arms (2)

Phase I: Sequential Pharmacological PTIS

EXPERIMENTAL

Drug: Fludarabine; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Rituximab; Drug: Busulfan; Drug: Cyclophosphamide (Cy); Drug: Tacrolimus (or cyclosporine)

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

EXPERIMENTAL

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Busulfan; Drug: Cyclophosphamide (Cy); Drug: Tacrolimus (or cyclosporine); Drug: Mycophenolate mofetil (MMF); Drug: Rabbit ATG

Interventions

Fludarabine DRUG

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

Also known as: Fludara™

Phase I: Sequential Pharmacological PTIS; Phase II: RTC Regimen and GVHD Prophylaxis Based on Post-Cy

Dexamethasone DRUG

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

Phase I: Sequential Pharmacological PTIS

Cyclophosphamide DRUG

100 mg/m2 IV-by vein

Also known as: Cytoxan™

Phase I: Sequential Pharmacological PTIS; Phase II: RTC Regimen and GVHD Prophylaxis Based on Post-Cy

Bortezomib DRUG

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

Also known as: Velcade®

Phase I: Sequential Pharmacological PTIS

Rituximab DRUG

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

Also known as: Rituxan®

Phase I: Sequential Pharmacological PTIS

Busulfan DRUG

110 mg/m2 i.v-by vein

Also known as: Busulfex™

Phase I: Sequential Pharmacological PTIS; Phase II: RTC Regimen and GVHD Prophylaxis Based on Post-Cy

Cyclophosphamide (Cy) DRUG

by vein

Also known as: Cytoxan™

Phase I: Sequential Pharmacological PTIS; Phase II: RTC Regimen and GVHD Prophylaxis Based on Post-Cy

Tacrolimus (or cyclosporine) DRUG

by vein

Phase I: Sequential Pharmacological PTIS; Phase II: RTC Regimen and GVHD Prophylaxis Based on Post-Cy

Mycophenolate mofetil (MMF) DRUG

given by PO

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

Rabbit ATG DRUG

by vein

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Interventions

fludarabine; fludarabine phosphate; Dexamethasone; Cyclophosphamide; Bortezomib; Rituximab; Busulfan; Tacrolimus; Cyclosporine; Mycophenolic Acid; thymoglobulin

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Macrolides; Lactones; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Jeremy Ramdial, Ramdial

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2022
• First Posted: March 24, 2022
• Study Start: March 2, 2022
• Primary Completion: September 18, 2023
• Study Completion: September 18, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Locations

US (1)