Clofarabine Pre-conditioning Followed by Stem Cell Transplant for Non-remission AML

NCT04002115 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-011
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The Investigators would like to study the incidence of complete remission (CR) at day +30 after Clofarabine followed by haploidentical transplant. The conditioning regimen used is Fludarabine, Busulfan (2 doses) or cyclophosphamide (2 doses) and Total Body Irradiation (TBI) with post transplant cyclophosphamide for patients with Acute Myeloid Leukemia (AML) who are not in remission prior to considering allogeneic transplant with haploidentical donors.

Conditions

Acute Myeloid Leukemia

Keywords

Clofarabine; Haploidentical stem cell transplantation; matched and mismatched unrelated donors; Non-remission AML

Outcome Measures

Primary Outcomes (1)

• Complete Remission (CR) Rate at Day 30 Post HSCT

  The CR rate at 30 days (Day +30) post stem cell transplant infusion

  30 days

Secondary Outcomes (6)

• Non-relapse Related Mortality

  100 days

• Neutrophil Engraftment

  1 year

• Rate of Acute Graft-versus-host Disease (GVHD)

  100 days

• Severity of Acute Graft-versus-host Disease (GVHD)

  100 days

• Rate of Chronic GVHD

  1 year

Study Arms (1)

Clofarabine 30 mg/m^2

EXPERIMENTAL

Day -14 through Day -10 Clofarabine 30 mg/m\^2, Day - 9 Day of rest, Day - 8 Day of rest, Day - 7 Day of rest, Day - 6 Fludarabine 40 mg/m\^2 IV and Busulfan 3.2 mg/kg IV (Regimen A, Fludarabine 24 mg/m\^2 IV and Cyclophosphamide 14.5 mg/kg IV for Regimen B), Day - 5 Fludarabine 40 mg/m\^2 IV and Busulfan 3.2 mg/kg IV (Regimen A, Fludarabine 24 mg/m\^2 IV and Cyclophosphamide 14.5 mg/kg IV for Regimen B), Day - 4 Fludarabine 40 mg/m\^2 IV(Regimen A, Fludarabine 24 mg/m\^2 IV for Regimen B), Day - 3 Fludarabine 40 mg/m\^2 IV(Regimen A, Fludarabine 24 mg/m\^2 IV for Regimen B), Day - 2 Day of Rest, Day -1 Total Body Irradiation 200 cGys, Day 0 stem cell transplant infusion, Day +1 Day of rest, Day +2 Day of rest, Day +3 Cyclophosphamide 50 mg/kg IV, Day +4 Cyclophosphamide 50 mg/kg IV, Day +5 Start G-CSF, Tacrolimus, and MMF.

Drug: Clofarabine; Drug: Fludarabine; Drug: Busulfan; Procedure: Total Body Irradiation (TBI); Drug: Cyclophosphamide; Drug: Granulocyte Colony-Stimulating Factor; Drug: Tacrolimus; Drug: Cellcept

Interventions

Clofarabine DRUG

Clofarabine to be administered pre-stem cell transplant infusion ("Day 0") once a day for 5 days total.

Also known as: Clolar

Clofarabine 30 mg/m^2

Fludarabine DRUG

Fludarabine will be administered once a day for 4 days as part of the transplant conditioning regimen.

Also known as: Fludara

Clofarabine 30 mg/m^2

Busulfan DRUG

Busulfan will be administered once a day for 2 days as part of the transplant conditioning regimen.

Also known as: Busulfex

Clofarabine 30 mg/m^2

Total Body Irradiation (TBI) PROCEDURE

TBI will be administered at a dose of 200cGys on Day -1 prior to transplant

Also known as: TBI

Clofarabine 30 mg/m^2

Cyclophosphamide DRUG

Cyclophosphamide will be given once a day for 2 days after the transplant infusion.

Also known as: Cytoxan

Clofarabine 30 mg/m^2

Granulocyte Colony-Stimulating Factor DRUG

G-CSF will be administered to subjects starting on Day +5 and will continue as clinically indicated

Also known as: Filgrastim G-CSF

Clofarabine 30 mg/m^2

Tacrolimus DRUG

Tacrolimus will be administered to subjects starting on Day +5 and will continue as clinically indicated

Also known as: Prograf

Clofarabine 30 mg/m^2

Cellcept DRUG

Mycophenolate Mofetil will be administered to subjects starting on Day +5 and will continue as clinically indicated

Also known as: Mycophenolate Mofetil (MMF)

Clofarabine 30 mg/m^2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnostic criteria of AML, induction failure without having achieved remission after at least 2 attempts at induction chemotherapy, or relapsed after any complete remission (CR).
• to 75 years of age.
• Planned or scheduled to receive an allogeneic HSCT from haploidentical related donors, matched and mismatched unrelated donors.
• All organ function testing should be done within 28 days of study registration.
• Performance status: Karnofsky ≥ 70% (Appendix A).
• Cardiac: LVEF ≥ 50% by MUGA or echocardiogram.
• Pulmonary: FEV1 and FVC ≥ 50% predicted, DLCO (corrected for hemoglobin) ≥ 50% of predicted.
• Renal: Creatinine clearance (CrCl) ≥ 60 mL/min/1.73 m2
• Hepatic: Serum bilirubin ≤1.5 x upper limit of normal (ULN); (AST)/(ALT) ≤ 2.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN.
• Both men and women need to use an approved method of birth control and/or abstinence due to unknown risks to the fetus.

You may not qualify if:

• Acute promyelocytic leukemia (APL)
• Known history of non-compliance with medication regimens, scheduled clinic visits, or self-care.
• In the opinion of the investigator, no appropriate caregivers identified.
• HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive
• Active Hepatitis B and Hepatitis C orepatitis positive serology including HBsAg, hepatitis B core antibody, and hepatitis C antibody. Hepatitis B surface antibody positive due to vaccination or natural immunity are permitted.
• In the opinion of the physician investigator, uncontrolled medical or psychiatric disorders.
• Uncontrolled infections requiring treatment within 14 days of registration.
• Active central nervous system (CNS) leukemia.
• Cord blood transplant excluded.
• Prior allogeneic HSCT within last 6 months.
• Patients with \>= grade 2 acute GVHD.
• Patients with \>=moderate chronic GVHD.
• Pregnant or Breastfeeding. Women of child bearing potential (WCBP) are required to have a negative serum or urine pregnancy test prior to initiation of conditioning regimen.
• Haploidentical related donors who are positive for DSA ≥ 5000 MFI by solid phase microarray method (Luminex).
• Any patient with steroid dose more than 10 mg/day within a week of registration .

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

Related Links

• Penn State Cancer Institute

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Clofarabine; fludarabine; fludarabine phosphate; Busulfan; Whole-Body Irradiation; Cyclophosphamide; Granulocyte Colony-Stimulating Factor; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Limitations and Caveats

Due to slow accrual, the study was terminated.

Results Point of Contact

• Title: Dr. Seema Naik
• Organization: Penn State Health

snaik@pennstatehealth.psu.edu

7175310003

Study Officials

• Seema Naik, MD

  Penn State Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of the Penn State Cancer Institute

Model Details: Dose de-escalation: Enrollment will begin at 30 mg/m2 to analyze any grade 4-5 organ toxicities as defined in Section 12.2. If the trial is stopped due to excessive toxicities, then dose de-escalation to 20 mg/m2 will occur for the next cohort of participants. For each participant, the observation period is from start of treatment through post-transplant day +30. Adverse effects will be continuously monitored as patients are enrolled. The trial will be stopped when the toxicity rate exceeds 20% with a posterior probability of 80% and a margin of no more than 5%. This leads to the following stopping rule: the trial will be stopped if 2 of the first 3 subjects experience grade 4-5 organ toxicity, or 3 out of 6, 4 out 9, 5 out of 12, 6 out of 16, or 7 out 19.

Study Record Dates

• First Submitted: June 24, 2019
• First Posted: June 28, 2019
• Study Start: June 3, 2020
• Primary Completion: August 30, 2022
• Study Completion: November 7, 2022
• Last Updated: September 14, 2023
• Results First Posted: September 14, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)